{ "generated_from": [ "data/research.json (vaccines/drugs/prevention)", "panel_state.csv, panel_county.csv, panel_country.csv (geography)" ], "coverage_threshold_pct": 85.0, "topic_question_count": 29, "geography_question_count": 43, "standing_caveat": "Vaccine, drug and prevention cards report what the individual-level studies in our library themselves found -- no new statistic is computed on this page for those topics. The geography cards below them are a different, weaker kind of evidence: an aggregate or modelled correlation between places. Neither half of this page is medical advice.", "counts": { "total": 72, "ready": 68, "blocked": 1, "topic_questions": 29, "geography_questions": 43 }, "studies": [ { "id": "VAX-1", "group": "vaccines", "question": "Herpes zoster (shingles) vaccination and dementia risk", "note": "The strongest individual-level evidence this library holds on any prevention question. Three of the five studies below are natural experiments: an age or birth-date eligibility cut-off for the free shingles vaccine gave two otherwise-similar groups different vaccine access, which is the closest this evidence gets to a randomised comparison without actually randomising anyone. All five are still observational cohorts, not trials -- the biological mechanism (viral reactivation and neuroinflammation is one hypothesis) is not established, and this describes the study groups, not a guarantee for any one person.", "n_studies": 13, "design_counts": { "systematic_review": 0, "meta_analysis": 1, "rct": 1, "cohort": 9, "case_control": 0, "cross_sectional": 0, "other": 2 }, "design_mix_text": "13 studies: Meta-analysis 1, RCT / clinical trial 1, Cohort 9, Other / not reported 2", "featured": [ { "title": "Association between vaccinations and risk of dementia: a systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/41269248/", "year": 2025, "journal": "Age and Ageing", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 104031186, "effect_size": "Herpes zoster vaccination RR 0.76 (95% CI 0.69-0.83) for any dementia", "pmid": "41269248", "doi": "10.1093/ageing/afaf331" }, { "title": "Herpes zoster vaccination and incident dementia in Canada: an analysis of natural experiments", "url": "https://pubmed.ncbi.nlm.nih.gov/41579903/", "year": 2026, "journal": "The Lancet Neurology", "study_design": "cohort", "design_label": "Cohort", "n_participants": 232124, "effect_size": "-2.0 percentage points (95% CI -3.5 to -0.4) absolute reduction in new dementia diagnoses over 5.5 years", "pmid": "41579903", "doi": "10.1016/S1474-4422(25)00455-7" }, { "title": "Herpes Zoster Vaccination and Dementia Occurrence (Australian natural experiment)", "url": "https://pubmed.ncbi.nlm.nih.gov/40267506/", "year": 2025, "journal": "JAMA", "study_design": "cohort", "design_label": "Cohort", "n_participants": 101219, "effect_size": "-1.8 percentage points (95% CI -3.3 to -0.4) absolute reduction in new dementia diagnoses over 7.4 years for the vaccine-eligible group", "pmid": "40267506", "doi": "10.1001/jama.2025.5013" }, { "title": "Recombinant zoster vaccine is associated with a reduced risk of dementia", "url": "https://pubmed.ncbi.nlm.nih.gov/41663414/", "year": 2026, "journal": "Nature Communications", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 65800, "effect_size": "aHR: 0.49", "pmid": "41663414", "doi": "10.1038/s41467-026-69289-0" }, { "title": "Shingles, Zostavax vaccination and risk of developing dementia: a nested case-control study-results from the UK Biobank cohort", "url": "https://pubmed.ncbi.nlm.nih.gov/34625411/", "year": 2021, "journal": "BMJ open", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 2378, "effect_size": "OR: 1.088; OR: 0.808", "pmid": "34625411", "doi": "10.1136/bmjopen-2020-045871" }, { "title": "A natural experiment on the effect of herpes zoster vaccination on dementia (Wales)", "url": "https://pubmed.ncbi.nlm.nih.gov/40175543/", "year": 2025, "journal": "Nature", "study_design": "cohort", "design_label": "Cohort", "n_participants": null, "effect_size": "-3.5 percentage points (95% CI -7.1 to -0.6) in 7-year dementia diagnosis probability; 20.0% relative reduction (95% CI 6.5-33.4)", "pmid": "40175543", "doi": "10.1038/s41586-025-08800-x" }, { "title": "Impact of herpes zoster vaccination on incident dementia: A retrospective study in two patient cohorts", "url": "https://pubmed.ncbi.nlm.nih.gov/34788293/", "year": 2021, "journal": "PloS one", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 136016, "effect_size": "4.0%; 91.2%; 20.2%", "pmid": "34788293", "doi": "10.1371/journal.pone.0257405" }, { "title": "Charting the research frontier for viral infections, immunomodulation, and dementia: a perspective on synaptic biomarkers as essential clinical trial endpoints", "url": "https://pubmed.ncbi.nlm.nih.gov/41561087/", "year": 2026, "journal": "Frontiers in Cellular and Infection Microbiology", "study_design": "randomized controlled trial", "design_label": "RCT / clinical trial", "n_participants": null, "effect_size": "", "pmid": "41561087", "doi": "10.3389/fcimb.2025.1701760" }, { "title": "Lower risk of dementia with AS01-adjuvanted vaccination against shingles and respiratory syncytial virus infections", "url": "https://pubmed.ncbi.nlm.nih.gov/40562756/", "year": 2025, "journal": "npj Vaccines", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 436788, "effect_size": "", "pmid": "40562756", "doi": "10.1038/s41541-025-01172-3" }, { "title": "Adult Vaccination History and Plasma Biomarker Signatures in the Asymptomatic PREVENT-AD Cohort", "url": "https://doi.org/10.64898/2026.08.24.26361238", "year": 2026, "journal": "medRxiv (preprint)", "study_design": "longitudinal study", "design_label": "Cohort", "n_participants": 192, "effect_size": "", "pmid": "", "doi": "10.64898/2026.08.24.26361238" }, { "title": "Varicella-zoster virus reactivation and the risk of dementia", "url": "https://pubmed.ncbi.nlm.nih.gov/41053450/", "year": 2025, "journal": "Nature Medicine", "study_design": "longitudinal study", "design_label": "Cohort", "n_participants": null, "effect_size": "", "pmid": "41053450", "doi": "10.1038/s41591-025-03972-5" }, { "title": "Can the herpes zoster vaccination be a strategy against dementia?", "url": "https://pubmed.ncbi.nlm.nih.gov/40350295/", "year": 2025, "journal": "Drug Discoveries & Therapeutics", "study_design": "cohort study", "design_label": "Cohort", "n_participants": null, "effect_size": "", "pmid": "40350295", "doi": "10.5582/ddt.2025.01032" }, { "title": "Herpes zoster as risk factor for dementia: a matched cohort study over 20 years in a 10-million population in Italy", "url": "https://pubmed.ncbi.nlm.nih.gov/40222838/", "year": 2025, "journal": "The Journal of Prevention of Alzheimer s Disease", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 132968, "effect_size": "", "pmid": "40222838", "doi": "10.1016/j.tjpad.2025.100167" } ], "verdict": "ready", "blocked_by": null, "svg": "Shingles vaccination and new dementia diagnoses, three natural experimentsWales: 3.5 percentage-point reduction (95% CI 0.6 to 7.1); Canada: 2.0 percentage-point reduction (95% CI 0.4 to 3.5); Australia: 1.8 percentage-point reduction (95% CI 0.4 to 3.3)00.511.522.533.544.555.566.577.5percentage-point reduction in new dementia diagnosesWales3.5 ppCanada2 ppAustralia1.8 ppWhisker is the study's own 95% confidence interval. Each is a natural experiment: aneligibility cut-off (age or birth date) that made vaccination available to one group andnot an otherwise-similar neighbouring group.Observational, not a randomised trial -- the mechanism is not established, and thisdescribes the study groups, not any one person's certain outcome.", "svg_caption": "Source: each study's own reported effect size. Bars show the absolute drop in new dementia diagnoses for the vaccine-eligible group; whiskers are each study's own 95% confidence interval.", "svg_alt": "Bar chart: shingles vaccination and reduction in new dementia diagnoses across three natural-experiment studies (Australia, Wales, Canada), each roughly a 2 to 3.5 percentage-point drop, with confidence intervals shown.", "class_label": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "group_title": "Vaccines", "group_intro": "Vaccination status is recorded in an individual's own medical record, and dementia diagnosis is recorded in that same person -- an individual-level exposure and an individual-level outcome, the kind of evidence this site's library is actually built from. The strongest cards below are natural experiments; the weakest is a stated gap.", "is_group_first": true }, { "id": "VAX-2", "group": "vaccines", "question": "Influenza, pneumococcal and Tdap vaccination and dementia risk", "note": "Pooled observational evidence, from the same systematic review that covers the shingles vaccine above. The direction is consistent across every vaccine type studied, but these are not natural experiments -- a healthier person is generally more likely to get any vaccine, which can inflate an observational estimate like these.", "n_studies": 3, "design_counts": { "systematic_review": 0, "meta_analysis": 1, "rct": 0, "cohort": 2, "case_control": 0, "cross_sectional": 0, "other": 0 }, "design_mix_text": "3 studies: Meta-analysis 1, Cohort 2", "featured": [ { "title": "Association between vaccinations and risk of dementia: a systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/41269248/", "year": 2025, "journal": "Age and Ageing", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 104031186, "effect_size": "Herpes zoster vaccination RR 0.76 (95% CI 0.69-0.83) for any dementia", "pmid": "41269248", "doi": "10.1093/ageing/afaf331" }, { "title": "Recombinant zoster vaccine is associated with a reduced risk of dementia", "url": "https://pubmed.ncbi.nlm.nih.gov/41663414/", "year": 2026, "journal": "Nature Communications", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 65800, "effect_size": "aHR: 0.49", "pmid": "41663414", "doi": "10.1038/s41467-026-69289-0" }, { "title": "Varicella-zoster virus reactivation and the risk of dementia", "url": "https://pubmed.ncbi.nlm.nih.gov/41053450/", "year": 2025, "journal": "Nature Medicine", "study_design": "longitudinal study", "design_label": "Cohort", "n_participants": null, "effect_size": "", "pmid": "41053450", "doi": "10.1038/s41591-025-03972-5" } ], "verdict": "ready", "blocked_by": null, "svg": "Relative risk of dementia by vaccine type, pooled meta-analysisHerpes zoster (dementia): RR 0.76 (95% CI 0.69-0.83); Herpes zoster (Alzheimer's disease): RR 0.53 (95% CI 0.44-0.64); Influenza (dementia): RR 0.87 (95% CI 0.77-0.99); Pneumococcal (dementia): RR 0.64 (95% CI 0.47-0.87); Tdap (dementia): RR 0.67 (95% CI 0.54-0.83)00.20.50.81.0 = no associationHerpes zoster (dementia)RR 0.8Herpes zoster (Alzheimer's disease)RR 0.5Influenza (dementia)RR 0.9Pneumococcal (dementia)RR 0.6Tdap (dementia)RR 0.7All from one pooled meta-analysis of 21 observational studies. Vaccinated and unvaccinatedadults differ in ways beyond the vaccine itself (a healthier person is more likely to getvaccinated), which can inflate an observational estimate like this one.", "svg_caption": "Source: key findings reported in the meta-analysis itself. Bars run from the reported relative risk to 1.0 (no association); lower is fewer dementia diagnoses among the vaccinated.", "svg_alt": "Bar chart: relative risk of dementia for influenza, pneumococcal and Tdap vaccination from a pooled meta-analysis, all below 1.0, meaning lower risk among the vaccinated in these observational studies.", "class_label": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "VAX-3", "group": "vaccines", "question": "COVID-19 vaccination and dementia risk", "note": "A gap, stated plainly rather than filled with a plausible-sounding number: this library has no individual-level study measuring dementia risk by COVID-19 vaccination status. The COVID-vaccine studies it does hold measure death, hospitalisation or breakthrough infection -- real outcomes, just not this one.", "n_studies": 0, "design_counts": { "systematic_review": 0, "meta_analysis": 0, "rct": 0, "cohort": 0, "case_control": 0, "cross_sectional": 0, "other": 0 }, "design_mix_text": "0 matching studies", "featured": [], "verdict": "blocked", "blocked_by": "No study in our library measures dementia risk by COVID-19 vaccination status.", "svg": null, "svg_caption": "", "svg_alt": "", "class_label": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-1", "group": "drugs", "question": "Lecanemab and cognitive/functional decline", "note": "Approved on the strength of randomised trials showing a modest slowing of decline versus placebo in early Alzheimer's disease. Carries a boxed safety warning for brain swelling or bleeding (ARIA), monitored by MRI during treatment.", "class_label": "Approved (FDA, 2023) — anti-amyloid monoclonal antibody", "n_studies": 111, "design_counts": { "systematic_review": 9, "meta_analysis": 3, "rct": 14, "cohort": 7, "case_control": 1, "cross_sectional": 2, "other": 75 }, "design_mix_text": "111 studies: Systematic review 9, Meta-analysis 3, RCT / clinical trial 14, Cohort 7, Case-control 1, Cross-sectional 2, Other / not reported 75", "featured": [ { "title": "Amyloid-Related Imaging Abnormalities (ARIA) in Anti-Amyloid Therapies for Alzheimer's Disease: An Update from the Alzheimer's Association ARIA Workgroup", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13099593/", "year": 2026, "journal": "Alzheimer's & Dementia", "study_design": "systematic-review", "design_label": "Systematic review", "n_participants": null, "effect_size": "ARIA-E/ARIA-H rates: ~12.6%/17.3% (lecanemab) vs. ~24%/31% (donanemab) in pivotal trials; ApoE4 homozygotes ~2.5-5x higher risk", "pmid": "", "doi": "" }, { "title": "Cost-effectiveness of traditional and novel neurotherapeutic agents for Alzheimer's disease: A systematic review", "url": "https://pubmed.ncbi.nlm.nih.gov/41837605/", "year": 2026, "journal": "Journal of Alzheimer's Disease", "study_design": "systematic-review", "design_label": "Systematic review", "n_participants": null, "effect_size": "Anti-amyloid antibodies not cost-effective in any of 23 studies; value-based prices below $5,960-$33,700 per year at $150,000/QALY", "pmid": "41837605", "doi": "10.1177/13872877261430376" }, { "title": "Anti-Amyloid Monoclonal Antibodies and Amyloid-Related Imaging Abnormalities in Early Alzheimer Disease", "url": "https://doi.org/10.5281/zenodo.22310606", "year": 2026, "journal": "Zenodo (CERN European Organization for Nuclear Research)", "study_design": "narrative review", "design_label": "Systematic review", "n_participants": null, "effect_size": "12.6%", "pmid": "", "doi": "10.5281/zenodo.22310606" }, { "title": "Anti-Amyloid Monoclonal Antibodies and Amyloid-Related Imaging Abnormalities in Early Alzheimer Disease", "url": "https://doi.org/10.5281/zenodo.22310607", "year": 2026, "journal": "Zenodo (CERN European Organization for Nuclear Research)", "study_design": "narrative review", "design_label": "Systematic review", "n_participants": null, "effect_size": "12.6%", "pmid": "", "doi": "10.5281/zenodo.22310607" }, { "title": "Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/38253509/", "year": 2024, "journal": "Annals of Family Medicine", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 23202, "effect_size": "CDR-SB mean difference -0.18 (95% CI -0.34 to -0.03), below the MCID; ARIA-oedema NNH 9", "pmid": "38253509", "doi": "10.1370/afm.3050" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": "Study designs behind each drug, individual-level evidence onlyLecanemab and cognitive/functional decline: 111 studies: Systematic review 9, Meta-analysis 3, RCT / clinical trial 14, Cohort 7, Case-control 1, Cross-sectional 2, Other / not reported 75; Donanemab and cognitive/functional decline: 74 studies: Systematic review 9, Meta-analysis 3, RCT / clinical trial 10, Cohort 4, Other / not reported 48; Donepezil and symptom progression: 96 studies: Systematic review 4, Meta-analysis 3, RCT / clinical trial 12, Cohort 2, Cross-sectional 1, Other / not reported 74; Memantine and symptom progression: 94 studies: Systematic review 5, Meta-analysis 6, RCT / clinical trial 8, Cohort 7, Other / not reported 68; Galantamine and symptom progression: 38 studies: Systematic review 4, Meta-analysis 2, RCT / clinical trial 5, Cohort 1, Other / not reported 26; Rivastigmine and symptom progression: 42 studies: Systematic review 4, Meta-analysis 2, RCT / clinical trial 3, Other / not reported 33; Semaglutide / GLP-1 receptor agonists and dementia risk: 43 studies: Systematic review 1, Meta-analysis 4, RCT / clinical trial 5, Cohort 8, Other / not reported 25; Statins and dementia risk: 42 studies: Systematic review 3, Meta-analysis 2, RCT / clinical trial 6, Cohort 8, Case-control 1, Cross-sectional 2, Other / not reported 20; Metformin and dementia risk: 27 studies: Meta-analysis 5, Cohort 6, Case-control 1, Cross-sectional 1, Other / not reported 14; SSRIs and Alzheimer's-related outcomes: 31 studies: Systematic review 1, Meta-analysis 2, RCT / clinical trial 3, Cohort 3, Other / not reported 22; Sildenafil / PDE5 inhibitors and dementia risk: 6 studies: RCT / clinical trial 2, Other / not reported 4; NSAIDs and dementia risk: 36 studies: Systematic review 1, Meta-analysis 2, RCT / clinical trial 3, Cohort 4, Other / not reported 260%25%50%75%100%Lecanemab andcognitive/functional declinen=111Donanemab andcognitive/functional declinen=74Donepezil and symptomprogressionn=96Memantine and symptomprogressionn=94Galantamine and symptomprogressionn=38Rivastigmine and symptomprogressionn=42Semaglutide / GLP-1 receptoragonists and dementia riskn=43Statins and dementia riskn=42Metformin and dementia riskn=27SSRIs and Alzheimer's-relatedoutcomesn=31Sildenafil / PDE5 inhibitors anddementia riskn=6NSAIDs and dementia riskn=36Systematic reviewMeta-analysisRCT / clinical trialCohortCase-controlCross-sectionalOther / not reportedDarker is higher up the evidence pyramid; grey is not reported.", "group_chart_alt": "Stacked bar chart showing the mix of study designs (systematic review, meta-analysis, RCT, cohort, case-control, cross-sectional) for each of the twelve drug topics on this page.", "group_chart_caption": "Source: the study design each matching record states. Darker segments are higher up the evidence pyramid.", "group_title": "Drugs", "group_intro": "Two FDA-approved anti-amyloid antibodies have randomised-trial evidence of slowing decline; four older drugs are approved for symptom management only; the rest are repurposed candidates under investigation, not approved for Alzheimer's. Each card says which is which before it shows a single number.", "is_group_first": true }, { "id": "RX-2", "group": "drugs", "question": "Donanemab and cognitive/functional decline", "note": "Approved on the same basis as lecanemab: randomised trials showing a modest slowing of decline in early Alzheimer's disease, with the same ARIA monitoring requirement.", "class_label": "Approved (FDA, 2024) — anti-amyloid monoclonal antibody", "n_studies": 74, "design_counts": { "systematic_review": 9, "meta_analysis": 3, "rct": 10, "cohort": 4, "case_control": 0, "cross_sectional": 0, "other": 48 }, "design_mix_text": "74 studies: Systematic review 9, Meta-analysis 3, RCT / clinical trial 10, Cohort 4, Other / not reported 48", "featured": [ { "title": "Amyloid-Related Imaging Abnormalities (ARIA) in Anti-Amyloid Therapies for Alzheimer's Disease: An Update from the Alzheimer's Association ARIA Workgroup", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13099593/", "year": 2026, "journal": "Alzheimer's & Dementia", "study_design": "systematic-review", "design_label": "Systematic review", "n_participants": null, "effect_size": "ARIA-E/ARIA-H rates: ~12.6%/17.3% (lecanemab) vs. ~24%/31% (donanemab) in pivotal trials; ApoE4 homozygotes ~2.5-5x higher risk", "pmid": "", "doi": "" }, { "title": "Cost-effectiveness of traditional and novel neurotherapeutic agents for Alzheimer's disease: A systematic review", "url": "https://pubmed.ncbi.nlm.nih.gov/41837605/", "year": 2026, "journal": "Journal of Alzheimer's Disease", "study_design": "systematic-review", "design_label": "Systematic review", "n_participants": null, "effect_size": "Anti-amyloid antibodies not cost-effective in any of 23 studies; value-based prices below $5,960-$33,700 per year at $150,000/QALY", "pmid": "41837605", "doi": "10.1177/13872877261430376" }, { "title": "Anti-Amyloid Monoclonal Antibodies and Amyloid-Related Imaging Abnormalities in Early Alzheimer Disease", "url": "https://doi.org/10.5281/zenodo.22310606", "year": 2026, "journal": "Zenodo (CERN European Organization for Nuclear Research)", "study_design": "narrative review", "design_label": "Systematic review", "n_participants": null, "effect_size": "12.6%", "pmid": "", "doi": "10.5281/zenodo.22310606" }, { "title": "Anti-Amyloid Monoclonal Antibodies and Amyloid-Related Imaging Abnormalities in Early Alzheimer Disease", "url": "https://doi.org/10.5281/zenodo.22310607", "year": 2026, "journal": "Zenodo (CERN European Organization for Nuclear Research)", "study_design": "narrative review", "design_label": "Systematic review", "n_participants": null, "effect_size": "12.6%", "pmid": "", "doi": "10.5281/zenodo.22310607" }, { "title": "Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/38253509/", "year": 2024, "journal": "Annals of Family Medicine", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 23202, "effect_size": "CDR-SB mean difference -0.18 (95% CI -0.34 to -0.03), below the MCID; ARIA-oedema NNH 9", "pmid": "38253509", "doi": "10.1370/afm.3050" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-3", "group": "drugs", "question": "Donepezil and symptom progression", "note": "Long-approved for symptomatic treatment: it can improve or stabilise symptoms for a period, but it does not modify the underlying disease course.", "class_label": "Approved (FDA, 1996) — cholinesterase inhibitor", "n_studies": 96, "design_counts": { "systematic_review": 4, "meta_analysis": 3, "rct": 12, "cohort": 2, "case_control": 0, "cross_sectional": 1, "other": 74 }, "design_mix_text": "96 studies: Systematic review 4, Meta-analysis 3, RCT / clinical trial 12, Cohort 2, Cross-sectional 1, Other / not reported 74", "featured": [ { "title": "Cost-effectiveness of traditional and novel neurotherapeutic agents for Alzheimer's disease: A systematic review", "url": "https://pubmed.ncbi.nlm.nih.gov/41837605/", "year": 2026, "journal": "Journal of Alzheimer's Disease", "study_design": "systematic-review", "design_label": "Systematic review", "n_participants": null, "effect_size": "Anti-amyloid antibodies not cost-effective in any of 23 studies; value-based prices below $5,960-$33,700 per year at $150,000/QALY", "pmid": "41837605", "doi": "10.1177/13872877261430376" }, { "title": "Donepezil for dementia due to Alzheimer's disease", "url": "https://pubmed.ncbi.nlm.nih.gov/29923184/", "year": 2018, "journal": "The Cochrane database of systematic reviews", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 8257, "effect_size": "OR 1.25; OR 1.59", "pmid": "29923184", "doi": "10.1002/14651858.cd001190.pub3" }, { "title": "Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/33704781/", "year": 2021, "journal": "The Cochrane database of systematic reviews", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 2193, "effect_size": "OR 1.95; OR 3.21; OR 1.57", "pmid": "33704781", "doi": "10.1002/14651858.cd013306.pub2" }, { "title": "Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials", "url": "https://pubmed.ncbi.nlm.nih.gov/21555634/", "year": 2011, "journal": "Archives of neurology", "study_design": "randomized controlled trial", "design_label": "RCT / clinical trial", "n_participants": 24, "effect_size": "25.0% to 50.0%; 80.0%", "pmid": "21555634", "doi": "10.1001/archneurol.2011.94" }, { "title": "Effect of a CYP2D6 polymorphism on the efficacy of donepezil in patients with Alzheimer disease", "url": "https://pubmed.ncbi.nlm.nih.gov/19738170/", "year": 2009, "journal": "Neurology", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 115, "effect_size": "58.7%; 34.8%", "pmid": "19738170", "doi": "10.1212/wnl.0b013e3181b6bbe3" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-4", "group": "drugs", "question": "Memantine and symptom progression", "note": "Approved for moderate-to-severe Alzheimer's, usually alongside a cholinesterase inhibitor. Symptomatic, not disease-modifying.", "class_label": "Approved (FDA, 2003) — NMDA-receptor antagonist", "n_studies": 94, "design_counts": { "systematic_review": 5, "meta_analysis": 6, "rct": 8, "cohort": 7, "case_control": 0, "cross_sectional": 0, "other": 68 }, "design_mix_text": "94 studies: Systematic review 5, Meta-analysis 6, RCT / clinical trial 8, Cohort 7, Other / not reported 68", "featured": [ { "title": "Cost-effectiveness of traditional and novel neurotherapeutic agents for Alzheimer's disease: A systematic review", "url": "https://pubmed.ncbi.nlm.nih.gov/41837605/", "year": 2026, "journal": "Journal of Alzheimer's Disease", "study_design": "systematic-review", "design_label": "Systematic review", "n_participants": null, "effect_size": "Anti-amyloid antibodies not cost-effective in any of 23 studies; value-based prices below $5,960-$33,700 per year at $150,000/QALY", "pmid": "41837605", "doi": "10.1177/13872877261430376" }, { "title": "Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/24828899/", "year": 2015, "journal": "Journal of neurology, neurosurgery, and psychiatry", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": null, "effect_size": "RR 1.19", "pmid": "24828899", "doi": "10.1136/jnnp-2014-307659" }, { "title": "Dementia medications and risk of falls, syncope, and related adverse events: meta-analysis of randomized controlled trials", "url": "https://pubmed.ncbi.nlm.nih.gov/21649634/", "year": 2011, "journal": "Journal of the American Geriatrics Society", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": null, "effect_size": "OR=0.88; OR=1.39; OR=1.13", "pmid": "21649634", "doi": "10.1111/j.1532-5415.2011.03450.x" }, { "title": "Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study)", "url": "https://pubmed.ncbi.nlm.nih.gov/22291741/", "year": 2011, "journal": "Archives of medical science : AMS", "study_design": "randomized controlled trial", "design_label": "RCT / clinical trial", "n_participants": 1052, "effect_size": "75.1%", "pmid": "22291741", "doi": "10.5114/aoms.2011.20612" }, { "title": "A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease", "url": "https://pubmed.ncbi.nlm.nih.gov/20837824/", "year": 2011, "journal": "Archives of neurology", "study_design": "randomized controlled trial", "design_label": "RCT / clinical trial", "n_participants": 29, "effect_size": "28.6%", "pmid": "20837824", "doi": "10.1001/archneurol.2010.229" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-5", "group": "drugs", "question": "Galantamine and symptom progression", "note": "Symptomatic treatment, same class and same limits as donepezil and rivastigmine.", "class_label": "Approved (FDA, 2001) — cholinesterase inhibitor", "n_studies": 38, "design_counts": { "systematic_review": 4, "meta_analysis": 2, "rct": 5, "cohort": 1, "case_control": 0, "cross_sectional": 0, "other": 26 }, "design_mix_text": "38 studies: Systematic review 4, Meta-analysis 2, RCT / clinical trial 5, Cohort 1, Other / not reported 26", "featured": [ { "title": "Cost-effectiveness of traditional and novel neurotherapeutic agents for Alzheimer's disease: A systematic review", "url": "https://pubmed.ncbi.nlm.nih.gov/41837605/", "year": 2026, "journal": "Journal of Alzheimer's Disease", "study_design": "systematic-review", "design_label": "Systematic review", "n_participants": null, "effect_size": "Anti-amyloid antibodies not cost-effective in any of 23 studies; value-based prices below $5,960-$33,700 per year at $150,000/QALY", "pmid": "41837605", "doi": "10.1177/13872877261430376" }, { "title": "Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/33704781/", "year": 2021, "journal": "The Cochrane database of systematic reviews", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 2193, "effect_size": "OR 1.95; OR 3.21; OR 1.57", "pmid": "33704781", "doi": "10.1002/14651858.cd013306.pub2" }, { "title": "Disparity of Prescribed Psychotropics in Alzheimer’s Disease with Neuropsychiatric Symptoms", "url": "https://doi.org/10.3390/pharma5010001", "year": 2025, "journal": "Pharmacoepidemiology", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 6237, "effect_size": "OR = 1.538; OR = 1.222; OR = 2.323", "pmid": "", "doi": "10.3390/pharma5010001" }, { "title": "Bupropion for the Treatment of Apathy in Alzheimer Disease: A Randomized Clinical Trial", "url": "https://pubmed.ncbi.nlm.nih.gov/32463470/", "year": 2020, "journal": "JAMA network open", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 108, "effect_size": "72.2%; 61.1%; 9.3%", "pmid": "32463470", "doi": "10.1001/jamanetworkopen.2020.6027" }, { "title": "Cholinesterase inhibitors for patients with dementia: Patterns of prescribing and disparities in treatment", "url": "https://pubmed.ncbi.nlm.nih.gov/41527747/", "year": 2026, "journal": "Journal of Alzheimer s Disease", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": null, "effect_size": "OR: 0.34; OR: 0.81; OR: 0.74", "pmid": "41527747", "doi": "10.1177/13872877251411418" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-6", "group": "drugs", "question": "Rivastigmine and symptom progression", "note": "Symptomatic treatment, same class and same limits as donepezil and galantamine.", "class_label": "Approved (FDA, 2000) — cholinesterase inhibitor", "n_studies": 42, "design_counts": { "systematic_review": 4, "meta_analysis": 2, "rct": 3, "cohort": 0, "case_control": 0, "cross_sectional": 0, "other": 33 }, "design_mix_text": "42 studies: Systematic review 4, Meta-analysis 2, RCT / clinical trial 3, Other / not reported 33", "featured": [ { "title": "Cost-effectiveness of traditional and novel neurotherapeutic agents for Alzheimer's disease: A systematic review", "url": "https://pubmed.ncbi.nlm.nih.gov/41837605/", "year": 2026, "journal": "Journal of Alzheimer's Disease", "study_design": "systematic-review", "design_label": "Systematic review", "n_participants": null, "effect_size": "Anti-amyloid antibodies not cost-effective in any of 23 studies; value-based prices below $5,960-$33,700 per year at $150,000/QALY", "pmid": "41837605", "doi": "10.1177/13872877261430376" }, { "title": "Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/33704781/", "year": 2021, "journal": "The Cochrane database of systematic reviews", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 2193, "effect_size": "OR 1.95; OR 3.21; OR 1.57", "pmid": "33704781", "doi": "10.1002/14651858.cd013306.pub2" }, { "title": "Efficacy of rivastigmine for cognitive symptoms in Parkinson disease with dementia", "url": "https://pubmed.ncbi.nlm.nih.gov/19590387/", "year": 2009, "journal": "The neurologist", "study_design": "randomized controlled trial", "design_label": "RCT / clinical trial", "n_participants": 541, "effect_size": "5.3%", "pmid": "19590387", "doi": "10.1097/nrl.0b013e3181a968df" }, { "title": "Effectiveness of the 10 cm2 Rivastigmine Patch in Taiwanese Patients with Mild-to-Moderate Alzheimer's Dementia: A 48-Week Real-World Observational Study", "url": "https://pubmed.ncbi.nlm.nih.gov/34506009/", "year": 2021, "journal": "Advances in therapy", "study_design": "open-label trial", "design_label": "RCT / clinical trial", "n_participants": null, "effect_size": "75.8%; 63.2%; 89.8%", "pmid": "34506009", "doi": "10.1007/s12325-021-01893-6" }, { "title": "Rivastigmine for Alzheimer's disease", "url": "https://pubmed.ncbi.nlm.nih.gov/25858345/", "year": 2015, "journal": "The Cochrane database of systematic reviews", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 3232, "effect_size": "or 9.5; OR 0.68; OR 2.16", "pmid": "25858345", "doi": "10.1002/14651858.cd001191.pub3" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-7", "group": "drugs", "question": "Semaglutide / GLP-1 receptor agonists and dementia risk", "note": "The two largest phase-3 trials of oral semaglutide in early symptomatic Alzheimer's (EVOKE/EVOKE+) did not show a significant benefit over placebo. Cohort studies of GLP-1 drugs in diabetes populations show a smaller dementia risk that has not reached statistical significance in the studies below -- read the trial and the cohort evidence as separate questions, not as confirming each other.", "class_label": "Investigational — repurposed from diabetes/obesity care; not approved for Alzheimer's", "n_studies": 43, "design_counts": { "systematic_review": 1, "meta_analysis": 4, "rct": 5, "cohort": 8, "case_control": 0, "cross_sectional": 0, "other": 25 }, "design_mix_text": "43 studies: Systematic review 1, Meta-analysis 4, RCT / clinical trial 5, Cohort 8, Other / not reported 25", "featured": [ { "title": "Anti-diabetic agents and the risks of dementia in patients with type 2 diabetes: a systematic review and network meta-analysis of observational studies and randomized controlled trials", "url": "https://pubmed.ncbi.nlm.nih.gov/39716328/", "year": 2024, "journal": "Alzheimer's Research & Therapy", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 3462926, "effect_size": "Observational: SGLT2i OR 0.56 (95% CI 0.45-0.69), GLP-1RA OR 0.58 (0.46-0.73) vs non-users; RCTs: no difference", "pmid": "39716328", "doi": "10.1186/s13195-024-01645-y" }, { "title": "What Do Sugar, Gila Monsters, and the Therapeutic Dance Have in Common With GLP-1RA, Stroke, and Dementia?", "url": "https://doi.org/10.1212/nxg.0000000000200450", "year": 2026, "journal": "Neurology Genetics", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 74148, "effect_size": "RR 0.73", "pmid": "", "doi": "10.1212/nxg.0000000000200450" }, { "title": "Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/40193122/", "year": 2025, "journal": "JAMA neurology", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 164, "effect_size": "34.9%", "pmid": "40193122", "doi": "10.1001/jamaneurol.2025.0360" }, { "title": "Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (EVOKE and EVOKE+): two phase 3, randomised, placebo-controlled trials", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00459-9/fulltext", "year": 2026, "journal": "The Lancet", "study_design": "phase-3-trial", "design_label": "RCT / clinical trial", "n_participants": 3808, "effect_size": "EVOKE difference -0.08 (95% CI -0.35 to 0.20); EVOKE+ difference 0.10 (95% CI -0.17 to 0.38)", "pmid": "", "doi": "" }, { "title": "Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial", "url": "https://pubmed.ncbi.nlm.nih.gov/41326666/", "year": 2025, "journal": "Nature Medicine", "study_design": "phase-2-trial", "design_label": "RCT / clinical trial", "n_participants": 204, "effect_size": "Cerebral glucose metabolism difference -0.17 (95% CI -0.39 to 0.06, p=0.14); CDR-SB -0.06 (95% CI -0.57 to 0.44)", "pmid": "41326666", "doi": "10.1038/s41591-025-04106-7" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-8", "group": "drugs", "question": "Statins and dementia risk", "note": "Observational studies are mixed on direction and size; a target-trial-emulation design is among the strongest designs below, which is a genuine strength for an observational question like this one.", "class_label": "Investigational — repurposed from cardiovascular care; not approved for Alzheimer's", "n_studies": 42, "design_counts": { "systematic_review": 3, "meta_analysis": 2, "rct": 6, "cohort": 8, "case_control": 1, "cross_sectional": 2, "other": 20 }, "design_mix_text": "42 studies: Systematic review 3, Meta-analysis 2, RCT / clinical trial 6, Cohort 8, Case-control 1, Cross-sectional 2, Other / not reported 20", "featured": [ { "title": "Statins for the prevention of dementia", "url": "https://pubmed.ncbi.nlm.nih.gov/26727124/", "year": 2016, "journal": "The Cochrane database of systematic reviews", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 26340, "effect_size": "OR 0.94", "pmid": "26727124", "doi": "10.1002/14651858.cd003160.pub3" }, { "title": "Statin use and risk of dementia or Alzheimer's disease: a systematic review and meta-analysis of observational studies", "url": "https://pubmed.ncbi.nlm.nih.gov/34871380/", "year": 2022, "journal": "European journal of preventive cardiology", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": null, "effect_size": "OR 0.80; OR 0.68; OR 0.86", "pmid": "34871380", "doi": "10.1093/eurjpc/zwab208" }, { "title": "Statin Initiation and Dementia Incidence in a Large Health Care System From 1997 to 2020: A Target Trial Emulation Study", "url": "https://pubmed.ncbi.nlm.nih.gov/40577672/", "year": 2025, "journal": "Neurology", "study_design": "cohort", "design_label": "Cohort", "n_participants": 322358, "effect_size": "HR 1.00 (95% CI 0.99-1.01) for dementia after the first year of statin initiation", "pmid": "40577672", "doi": "10.1212/WNL.0000000000213855" }, { "title": "Statin Initiation and Risk of Incident Alzheimer Disease and Cognitive Decline in Genetically Susceptible Older Adults", "url": "https://pubmed.ncbi.nlm.nih.gov/38447103/", "year": 2024, "journal": "Neurology", "study_design": "cohort", "design_label": "Cohort", "n_participants": 4807, "effect_size": "Alzheimer's HR 0.81 (95% CI 0.70-0.94) overall; 0.60 (0.49-0.74) in APOE ε4 carriers; 0.96 (0.82-1.12) in non-carriers", "pmid": "38447103", "doi": "10.1212/WNL.0000000000209168" }, { "title": "Use of lipid-lowering drugs in older adults with and without dementia: a community-based epidemiological study", "url": "https://pubmed.ncbi.nlm.nih.gov/12410906/", "year": 2002, "journal": "Journal of the American Geriatrics Society", "study_design": "longitudinal study", "design_label": "Cohort", "n_participants": null, "effect_size": "20.1%; 87.7%; 89.5%", "pmid": "12410906", "doi": "10.1046/j.1532-5415.2002.50515.x" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-9", "group": "drugs", "question": "Metformin and dementia risk", "note": "Observational and pooled evidence in people with diabetes; no completed Alzheimer's-specific trial in this library.", "class_label": "Investigational — repurposed from diabetes care; not approved for Alzheimer's", "n_studies": 27, "design_counts": { "systematic_review": 0, "meta_analysis": 5, "rct": 0, "cohort": 6, "case_control": 1, "cross_sectional": 1, "other": 14 }, "design_mix_text": "27 studies: Meta-analysis 5, Cohort 6, Case-control 1, Cross-sectional 1, Other / not reported 14", "featured": [ { "title": "Association of Metformin use with risk of dementia in patients with type 2 diabetes: A systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/39780315/", "year": 2025, "journal": "Diabetes, Obesity and Metabolism", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 3463100, "effect_size": "HR 0.76 (95% CI 0.65-0.91) vs non-users overall; HR 1.01 (0.81-1.27) in newly diagnosed diabetes", "pmid": "39780315", "doi": "10.1111/dom.16192" }, { "title": "Anti-diabetic agents and the risks of dementia in patients with type 2 diabetes: a systematic review and network meta-analysis of observational studies and randomized controlled trials", "url": "https://pubmed.ncbi.nlm.nih.gov/39716328/", "year": 2024, "journal": "Alzheimer's Research & Therapy", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 3462926, "effect_size": "Observational: SGLT2i OR 0.56 (95% CI 0.45-0.69), GLP-1RA OR 0.58 (0.46-0.73) vs non-users; RCTs: no difference", "pmid": "39716328", "doi": "10.1186/s13195-024-01645-y" }, { "title": "Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/40193122/", "year": 2025, "journal": "JAMA neurology", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 164, "effect_size": "34.9%", "pmid": "40193122", "doi": "10.1001/jamaneurol.2025.0360" }, { "title": "Antidiabetic medications and risk of cognitive disorders in type 2 diabetes: A retrospective cohort study", "url": "https://pubmed.ncbi.nlm.nih.gov/42636218/", "year": 2026, "journal": "PLoS ONE", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 1528885, "effect_size": "49.2%", "pmid": "42636218", "doi": "10.1371/journal.pone.0356138" }, { "title": "Metformin Cessation and Dementia Incidence", "url": "https://pubmed.ncbi.nlm.nih.gov/37878309/", "year": 2023, "journal": "JAMA Network Open", "study_design": "cohort", "design_label": "Cohort", "n_participants": 41346, "effect_size": "HR 1.21 (95% CI 1.12-1.30) for dementia after early metformin termination", "pmid": "37878309", "doi": "10.1001/jamanetworkopen.2023.39723" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-10", "group": "drugs", "question": "SSRIs and Alzheimer's-related outcomes", "note": "Most trials below study SSRIs for agitation or depression in people who already have Alzheimer's, not for preventing it -- a different question from the drug-repurposing angle above.", "class_label": "Investigational — not approved for preventing or treating Alzheimer's", "n_studies": 31, "design_counts": { "systematic_review": 1, "meta_analysis": 2, "rct": 3, "cohort": 3, "case_control": 0, "cross_sectional": 0, "other": 22 }, "design_mix_text": "31 studies: Systematic review 1, Meta-analysis 2, RCT / clinical trial 3, Cohort 3, Other / not reported 22", "featured": [ { "title": "Escitalopram for agitation in Alzheimer's dementia: a randomized controlled phase 3 trial", "url": "https://pubmed.ncbi.nlm.nih.gov/40133524/", "year": 2025, "journal": "Nature Medicine", "study_design": "phase-3-trial", "design_label": "RCT / clinical trial", "n_participants": 173, "effect_size": "Risk difference for clinically significant improvement 0.08 (95% CI -0.21 to 0.06)", "pmid": "40133524", "doi": "10.1038/s41591-025-03569-y" }, { "title": "Antidepressant use and cognitive decline in patients with dementia: a national cohort study", "url": "https://pubmed.ncbi.nlm.nih.gov/39994788/", "year": 2025, "journal": "BMC Medicine", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 18740, "effect_size": "54.5%; 22.8%; 64.8%", "pmid": "39994788", "doi": "10.1186/s12916-025-03851-3" }, { "title": "Disparity of Prescribed Psychotropics in Alzheimer’s Disease with Neuropsychiatric Symptoms", "url": "https://doi.org/10.3390/pharma5010001", "year": 2025, "journal": "Pharmacoepidemiology", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 6237, "effect_size": "OR = 1.538; OR = 1.222; OR = 2.323", "pmid": "", "doi": "10.3390/pharma5010001" }, { "title": "Is sertraline treatment or depression remission in depressed Alzheimer patients associated with improved caregiver well being? Depression in Alzheimer's Disease Study 2", "url": "https://pubmed.ncbi.nlm.nih.gov/24314887/", "year": 2014, "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 131, "effect_size": "63.4%; 64.1%", "pmid": "24314887", "doi": "10.1016/j.jagp.2013.02.014" }, { "title": "Sertraline for the treatment of depression in Alzheimer disease", "url": "https://pubmed.ncbi.nlm.nih.gov/20087081/", "year": 2010, "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 67, "effect_size": "OR = 1.01; OR = 2.06", "pmid": "20087081", "doi": "10.1097/jgp.0b013e3181c796eb" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-11", "group": "drugs", "question": "Sildenafil / PDE5 inhibitors and dementia risk", "note": "Only two studies in this library; read the numbers below as an early signal, not a settled finding.", "class_label": "Investigational — repurposed from erectile dysfunction/vascular care; not approved for Alzheimer's", "n_studies": 6, "design_counts": { "systematic_review": 0, "meta_analysis": 0, "rct": 2, "cohort": 0, "case_control": 0, "cross_sectional": 0, "other": 4 }, "design_mix_text": "6 studies: RCT / clinical trial 2, Other / not reported 4", "featured": [ { "title": "Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study", "url": "https://pubmed.ncbi.nlm.nih.gov/38324745/", "year": 2024, "journal": "Neurology", "study_design": "randomized controlled trial", "design_label": "RCT / clinical trial", "n_participants": 269725, "effect_size": "HR 0.56 (95% CI 0.43-0.73); HR 0.65 (95% CI 0.49-0.87); HR 0.82", "pmid": "38324745", "doi": "10.1212/wnl.0000000000209131" }, { "title": "Efficacy and Safety of Cilostazol in Mild Cognitive Impairment: A Randomized Clinical Trial", "url": "https://pubmed.ncbi.nlm.nih.gov/38048134/", "year": 2023, "journal": "JAMA network open", "study_design": "clinical trial", "design_label": "RCT / clinical trial", "n_participants": 159, "effect_size": "41.5%; 2.5%; 3.8%", "pmid": "38048134", "doi": "10.1001/jamanetworkopen.2023.44938" }, { "title": "Vascular Dementia: From Pathophysiology to Therapeutic Frontiers", "url": "https://pubmed.ncbi.nlm.nih.gov/41010812/", "year": 2025, "journal": "Journal of Clinical Medicine", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": null, "effect_size": "", "pmid": "41010812", "doi": "10.3390/jcm14186611" }, { "title": "Unifying Vascular Injury and Neurodegeneration: A Mechanistic Continuum in Cerebral Small Vessel Disease and Dementia", "url": "https://pubmed.ncbi.nlm.nih.gov/40913504/", "year": 2025, "journal": "European Journal of Neuroscience", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": null, "effect_size": "", "pmid": "40913504", "doi": "10.1111/ejn.70246" }, { "title": "Pharmacotherapy for Poststroke Cognitive Impairment and Poststroke Cognitive Impairment With Dementia: A Review", "url": "https://pubmed.ncbi.nlm.nih.gov/40421258/", "year": 2025, "journal": "Stroke Research and Treatment", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": null, "effect_size": "", "pmid": "40421258", "doi": "10.1155/srat/6893801" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "RX-12", "group": "drugs", "question": "NSAIDs and dementia risk", "note": "An older hypothesis (chronic anti-inflammatory use looked protective in early observational data) that randomised prevention trials below did not confirm -- a useful example of an observational signal that a trial did not reproduce.", "class_label": "Investigational — not approved for preventing Alzheimer's", "n_studies": 36, "design_counts": { "systematic_review": 1, "meta_analysis": 2, "rct": 3, "cohort": 4, "case_control": 0, "cross_sectional": 0, "other": 26 }, "design_mix_text": "36 studies: Systematic review 1, Meta-analysis 2, RCT / clinical trial 3, Cohort 4, Other / not reported 26", "featured": [ { "title": "NSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type", "url": "https://pubmed.ncbi.nlm.nih.gov/18003940/", "year": 2008, "journal": "Neurology", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 3229, "effect_size": "aHR 0.76; aHR 0.63; aHR 0.92", "pmid": "18003940", "doi": "10.1212/01.wnl.0000284596.95156.48" }, { "title": "Long‐Term Exposure to Non‐Steroidal Anti‐Inflammatory Medication in Relation to Dementia Risk", "url": "https://pubmed.ncbi.nlm.nih.gov/40040336/", "year": 2025, "journal": "Journal of the American Geriatrics Society", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 11745, "effect_size": "59.5%; 81.1%; HR: 1.04", "pmid": "40040336", "doi": "10.1111/jgs.19411" }, { "title": "Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT)", "url": "https://pubmed.ncbi.nlm.nih.gov/17111043/", "year": 2006, "journal": "PLoS clinical trials", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": 2528, "effect_size": "5.54%; 8.25%; 5.68%", "pmid": "17111043", "doi": "10.1371/journal.pctr.0010033" }, { "title": "rs140926439 Variant in the Fibronectin FN1 Gene Lowers Risk of Alzheimer Disease in APOEε4 Carriers in the UK Biobank Cohort", "url": "https://pubmed.ncbi.nlm.nih.gov/41195593/", "year": 2025, "journal": "Alzheimer Disease & Associated Disorders", "study_design": "not reported", "design_label": "Other / not reported", "n_participants": null, "effect_size": "0.10%; 0.43%", "pmid": "41195593", "doi": "10.1097/wad.0000000000000692" }, { "title": "Surgery, neuroinflammation and cognitive impairment", "url": "https://pubmed.ncbi.nlm.nih.gov/30348620/", "year": 2018, "journal": "EBioMedicine", "study_design": "narrative review", "design_label": "Systematic review", "n_participants": null, "effect_size": "", "pmid": "30348620", "doi": "10.1016/j.ebiom.2018.10.021" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "PREV-1", "group": "prevention", "question": "Physical activity / exercise", "note": "", "class_label": "", "n_studies": 134, "design_counts": { "systematic_review": 4, "meta_analysis": 16, "rct": 11, "cohort": 24, "case_control": 4, "cross_sectional": 10, "other": 65 }, "design_mix_text": "134 studies: Systematic review 4, Meta-analysis 16, RCT / clinical trial 11, Cohort 24, Case-control 4, Cross-sectional 10, Other / not reported 65", "featured": [ { "title": "Domain-specific physical activity levels and risk of dementia: a systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/42612650/", "year": 2026, "journal": "The Lancet. Public health", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 4227297, "effect_size": "RR 0.80 (95% CI 0.75-0.86) for all-cause dementia with high vs low physical activity; leisure-time RR 0.76 (0.65-0.88); occupational RR 1.20 (1.01-1.42)", "pmid": "42612650", "doi": "10.1016/S2468-2667(26)00142-8" }, { "title": "Effect of physical activity on risk of Alzheimer's disease: A systematic review and meta-analysis of twenty-nine prospective cohort studies", "url": "https://pubmed.ncbi.nlm.nih.gov/37979700/", "year": 2023, "journal": "Ageing Research Reviews", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 2068519, "effect_size": "Pooled HR 0.72 (95% CI 0.65-0.80) overall; HR 0.85 (95% CI 0.79-0.91) after maximal confounder adjustment; high-intensity activity HR 0.56 (95% CI 0.45-0.68); moderate-intensity HR 0.85 (95% CI 0.80-0.93); low-intensity HR 0.94 (95% CI 0.77-1.15, not significant)", "pmid": "", "doi": "" }, { "title": "Physical Activity and Cognitive Decline Among Older Adults: A Systematic Review and Meta-Analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/38300618/", "year": 2024, "journal": "JAMA Network Open", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 341471, "effect_size": "Pooled RR 0.97 (95% CI 0.97-0.99) for cognitive impairment/decline; no association beyond 10 years of follow-up", "pmid": "38300618", "doi": "10.1001/jamanetworkopen.2023.54285" }, { "title": "Physical activity as a protective factor for dementia and Alzheimer's disease: systematic review, meta-analysis and quality assessment of cohort and case-control studies", "url": "https://pubmed.ncbi.nlm.nih.gov/35301183/", "year": 2022, "journal": "British Journal of Sports Medicine", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 257983, "effect_size": "Pooled RR 0.80 (95% CI 0.77-0.84) for all-cause dementia", "pmid": "35301183", "doi": "10.1136/bjsports-2021-104981" }, { "title": "Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study", "url": "https://pubmed.ncbi.nlm.nih.gov/31335910/", "year": 2019, "journal": "PLoS medicine", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 48522, "effect_size": "58.4%", "pmid": "31335910", "doi": "10.1371/journal.pmed.1002853" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": "Study designs behind each modifiable risk factorPhysical activity / exercise: 134 studies: Systematic review 4, Meta-analysis 16, RCT / clinical trial 11, Cohort 24, Case-control 4, Cross-sectional 10, Other / not reported 65; Diet, including the Mediterranean/MIND diet: 122 studies: Systematic review 10, Meta-analysis 8, RCT / clinical trial 8, Cohort 22, Case-control 3, Cross-sectional 4, Other / not reported 67; Sleep: 82 studies: Systematic review 2, Meta-analysis 6, Cohort 11, Case-control 1, Cross-sectional 11, Other / not reported 51; Smoking: 89 studies: Systematic review 6, Meta-analysis 7, RCT / clinical trial 3, Cohort 21, Case-control 5, Cross-sectional 8, Other / not reported 39; Alcohol use: 67 studies: Systematic review 3, Meta-analysis 3, RCT / clinical trial 2, Cohort 19, Case-control 6, Cross-sectional 5, Other / not reported 29; Hearing loss and hearing aids: 50 studies: Systematic review 4, Meta-analysis 3, RCT / clinical trial 4, Cohort 18, Cross-sectional 4, Other / not reported 17; Social isolation and engagement: 45 studies: Systematic review 3, Meta-analysis 5, RCT / clinical trial 2, Cohort 9, Case-control 1, Cross-sectional 2, Other / not reported 23; Diabetes: 192 studies: Systematic review 4, Meta-analysis 13, RCT / clinical trial 4, Cohort 39, Case-control 6, Cross-sectional 9, Other / not reported 117; Hypertension / blood pressure: 157 studies: Systematic review 5, Meta-analysis 12, RCT / clinical trial 7, Cohort 33, Case-control 6, Cross-sectional 8, Other / not reported 86; Obesity / body mass index: 104 studies: Systematic review 2, Meta-analysis 11, RCT / clinical trial 4, Cohort 23, Case-control 2, Cross-sectional 7, Other / not reported 55; Depression: 116 studies: Systematic review 3, Meta-analysis 14, RCT / clinical trial 4, Cohort 26, Case-control 1, Cross-sectional 8, Other / not reported 60; Traumatic brain injury: 12 studies: Systematic review 2, RCT / clinical trial 1, Cohort 5, Case-control 1, Cross-sectional 2, Other / not reported 1; Education and cognitive reserve: 196 studies: Systematic review 5, Meta-analysis 12, RCT / clinical trial 8, Cohort 42, Case-control 6, Cross-sectional 19, Other / not reported 104; Air pollution (individual-level exposure): 26 studies: Systematic review 2, Meta-analysis 3, RCT / clinical trial 1, Cohort 4, Cross-sectional 3, Other / not reported 130%25%50%75%100%Physical activity / exercisen=134Diet, including theMediterranean/MIND dietn=122Sleepn=82Smokingn=89Alcohol usen=67Hearing loss and hearing aidsn=50Social isolation and engagementn=45Diabetesn=192Hypertension / blood pressuren=157Obesity / body mass indexn=104Depressionn=116Traumatic brain injuryn=12Education and cognitive reserven=196Air pollution (individual-levelexposure)n=26Systematic reviewMeta-analysisRCT / clinical trialCohortCase-controlCross-sectionalOther / not reportedDarker is higher up the evidence pyramid; grey is not reported.", "group_chart_alt": "Stacked bar chart showing the mix of study designs for each of the fourteen prevention and modifiable-risk-factor topics on this page.", "group_chart_caption": "Source: the study design each matching record states, for records filed under prevention or risk factors.", "group_title": "Prevention & modifiable risk factors", "group_intro": "Twelve of these fourteen topics are the modifiable risk factors named in the Lancet Commission's dementia-prevention framework (education, hearing loss, traumatic brain injury, hypertension, alcohol, obesity, smoking, depression, social isolation, physical inactivity, diabetes, air pollution), plus diet and sleep. Every count below is an individual-level study -- a person's own exposure, a person's own outcome -- not a place-level average.", "is_group_first": true }, { "id": "PREV-2", "group": "prevention", "question": "Diet, including the Mediterranean/MIND diet", "note": "", "class_label": "", "n_studies": 122, "design_counts": { "systematic_review": 10, "meta_analysis": 8, "rct": 8, "cohort": 22, "case_control": 3, "cross_sectional": 4, "other": 67 }, "design_mix_text": "122 studies: Systematic review 10, Meta-analysis 8, RCT / clinical trial 8, Cohort 22, Case-control 3, Cross-sectional 4, Other / not reported 67", "featured": [ { "title": "Association of mediterranean diet with mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/24164735/", "year": 2014, "journal": "Journal of Alzheimer's disease : JAD", "study_design": "systematic review", "design_label": "Systematic review", "n_participants": null, "effect_size": "HR = 0.67", "pmid": "24164735", "doi": "10.3233/jad-130830" }, { "title": "Association of the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet With the Risk of Dementia", "url": "https://pubmed.ncbi.nlm.nih.gov/37133875/", "year": 2023, "journal": "JAMA Psychiatry", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 224049, "effect_size": "HR 0.83 per 3-point MIND-score increment (95% CI 0.72-0.95); highest vs lowest tertile HR 0.83 (0.76-0.90)", "pmid": "37133875", "doi": "10.1001/jamapsychiatry.2023.0800" }, { "title": "Association between plant-based diets and incident dementia: results from prospective cohort studies and a meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/41564649/", "year": 2026, "journal": "The journal of prevention of Alzheimer's disease", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 207981, "effect_size": "Pooled HR for dementia, highest vs lowest tertile: overall PDI 0.70 (95% CI 0.53-0.92); unhealthful PDI 1.42 (95% CI 1.19-1.70)", "pmid": "41564649", "doi": "10.1016/j.tjpad.2025.100457" }, { "title": "Association between Mediterranean diet and dementia and Alzheimer disease: a systematic review with meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/38519775/", "year": 2024, "journal": "Aging Clinical and Experimental Research", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 65955, "effect_size": "Pooled OR 0.89 (95% CI 0.84-0.94) for dementia; cohort HR 0.84 (0.76-0.94); Alzheimer's OR 0.73 (0.62-0.85)", "pmid": "38519775", "doi": "10.1007/s40520-024-02718-6" }, { "title": "Effect of the Mediterranean diet on cognition and brain morphology and function: a systematic review of randomized controlled trials", "url": "https://pubmed.ncbi.nlm.nih.gov/29566197/", "year": 2018, "journal": "The American journal of clinical nutrition", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 1888, "effect_size": "12.1%; reduced by 78%; OR = 0.22", "pmid": "29566197", "doi": "10.1093/ajcn/nqx070" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "PREV-3", "group": "prevention", "question": "Sleep", "note": "", "class_label": "", "n_studies": 82, "design_counts": { "systematic_review": 2, "meta_analysis": 6, "rct": 0, "cohort": 11, "case_control": 1, "cross_sectional": 11, "other": 51 }, "design_mix_text": "82 studies: Systematic review 2, Meta-analysis 6, Cohort 11, Case-control 1, Cross-sectional 11, Other / not reported 51", "featured": [ { "title": "Insomnia and risk of dementia in older adults: Systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/27017287/", "year": 2016, "journal": "Journal of psychiatric research", "study_design": "systematic review", "design_label": "Systematic review", "n_participants": null, "effect_size": "RR = 1.53", "pmid": "27017287", "doi": "10.1016/j.jpsychires.2016.02.021" }, { "title": "Sleep apnea and the risk of dementia: A systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/35366021/", "year": 2022, "journal": "Journal of Sleep Research", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 1333424, "effect_size": "HR 1.43 (95% CI 1.26-1.62) for any neurocognitive disorder; Alzheimer's HR 1.28 (1.16-1.41)", "pmid": "35366021", "doi": "10.1111/jsr.13589" }, { "title": "Sleep disorders and the risk of cognitive decline or dementia: an updated systematic review and meta-analysis of longitudinal studies", "url": "https://pubmed.ncbi.nlm.nih.gov/41081870/", "year": 2025, "journal": "Journal of Neurology", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": null, "effect_size": "Excessive daytime sleepiness RR 1.41 for all-cause dementia; long sleep RR 1.66 for Alzheimer's disease", "pmid": "41081870", "doi": "10.1007/s00415-025-13372-x" }, { "title": "Sex differences in modifiable risk factors of dementia and their associations with cognition", "url": "https://pubmed.ncbi.nlm.nih.gov/42157293/", "year": 2026, "journal": "Biology of Sex Differences", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 17182, "effect_size": "59.2%", "pmid": "42157293", "doi": "10.1186/s13293-026-00908-7" }, { "title": "Association of sleep duration in middle and old age with incidence of dementia", "url": "https://www.nature.com/articles/s41467-021-22354-2", "year": 2021, "journal": "Nature Communications", "study_design": "cohort", "design_label": "Cohort", "n_participants": 7959, "effect_size": "HR ~1.22 (age 50) and ~1.37 (age 60) for short vs. 7-hour sleep; persistent short sleep across ages 50/60/70 ~30% higher risk", "pmid": "", "doi": "" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "PREV-4", "group": "prevention", "question": "Smoking", "note": "", "class_label": "", "n_studies": 89, "design_counts": { "systematic_review": 6, "meta_analysis": 7, "rct": 3, "cohort": 21, "case_control": 5, "cross_sectional": 8, "other": 39 }, "design_mix_text": "89 studies: Systematic review 6, Meta-analysis 7, RCT / clinical trial 3, Cohort 21, Case-control 5, Cross-sectional 8, Other / not reported 39", "featured": [ { "title": "Association of the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet With the Risk of Dementia", "url": "https://pubmed.ncbi.nlm.nih.gov/37133875/", "year": 2023, "journal": "JAMA Psychiatry", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 224049, "effect_size": "HR 0.83 per 3-point MIND-score increment (95% CI 0.72-0.95); highest vs lowest tertile HR 0.83 (0.76-0.90)", "pmid": "37133875", "doi": "10.1001/jamapsychiatry.2023.0800" }, { "title": "Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study", "url": "https://pubmed.ncbi.nlm.nih.gov/31335910/", "year": 2019, "journal": "PLoS medicine", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 48522, "effect_size": "58.4%", "pmid": "31335910", "doi": "10.1371/journal.pmed.1002853" }, { "title": "Risk Factors Associated With Alzheimer Disease and Related Dementias by Sex and Race and Ethnicity in the US", "url": "https://pubmed.ncbi.nlm.nih.gov/35532912/", "year": 2022, "journal": "JAMA neurology", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 378, "effect_size": "48.7%; 21.1%; 0.9%", "pmid": "35532912", "doi": "10.1001/jamaneurol.2022.0976" }, { "title": "Dietary Patterns and Risk of Dementia: a Systematic Review and Meta-Analysis of Cohort Studies", "url": "https://pubmed.ncbi.nlm.nih.gov/26553347/", "year": 2016, "journal": "Molecular neurobiology", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": null, "effect_size": "RR: 0.84; RR: 0.87; RR: 0.72", "pmid": "26553347", "doi": "10.1007/s12035-015-9516-4" }, { "title": "Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial", "url": "https://pubmed.ncbi.nlm.nih.gov/23732551/", "year": 2013, "journal": "The journal of nutrition, health & aging", "study_design": "randomized controlled trial", "design_label": "RCT / clinical trial", "n_participants": 285, "effect_size": "44.8%; OR=0.34", "pmid": "23732551", "doi": "10.1007/s12603-013-0027-6" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "PREV-5", "group": "prevention", "question": "Alcohol use", "note": "", "class_label": "", "n_studies": 67, "design_counts": { "systematic_review": 3, "meta_analysis": 3, "rct": 2, "cohort": 19, "case_control": 6, "cross_sectional": 5, "other": 29 }, "design_mix_text": "67 studies: Systematic review 3, Meta-analysis 3, RCT / clinical trial 2, Cohort 19, Case-control 6, Cross-sectional 5, Other / not reported 29", "featured": [ { "title": "Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study", "url": "https://pubmed.ncbi.nlm.nih.gov/31335910/", "year": 2019, "journal": "PLoS medicine", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 48522, "effect_size": "58.4%", "pmid": "31335910", "doi": "10.1371/journal.pmed.1002853" }, { "title": "Healthy lifestyle and the risk of Alzheimer dementia: Findings from 2 longitudinal studies", "url": "https://pubmed.ncbi.nlm.nih.gov/32554763/", "year": 2020, "journal": "Neurology", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 1845, "effect_size": "HR 0.63; 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92.49%", "pmid": "31743500", "doi": "10.1002/mds.27902" }, { "title": "Risk Factors Associated With Alzheimer Disease and Related Dementias by Sex and Race and Ethnicity in the US", "url": "https://pubmed.ncbi.nlm.nih.gov/35532912/", "year": 2022, "journal": "JAMA neurology", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 378, "effect_size": "48.7%; 21.1%; 0.9%", "pmid": "35532912", "doi": "10.1001/jamaneurol.2022.0976" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "PREV-12", "group": "prevention", "question": "Traumatic brain injury", "note": "", "class_label": "", "n_studies": 12, "design_counts": { "systematic_review": 2, "meta_analysis": 0, "rct": 1, "cohort": 5, "case_control": 1, "cross_sectional": 2, "other": 1 }, "design_mix_text": "12 studies: Systematic review 2, RCT / clinical trial 1, Cohort 5, Case-control 1, Cross-sectional 2, Other / not reported 1", "featured": [ { "title": "Timing of risk factors, prodromal features, and comorbidities of dementia from a large health claims case–control study", "url": "https://pubmed.ncbi.nlm.nih.gov/39819557/", "year": 2025, "journal": "Alzheimer s Research & Therapy", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 1686759, "effect_size": "61.70%", "pmid": "39819557", "doi": "10.1186/s13195-024-01662-x" }, { "title": "Traumatic brain injury and risk of dementia in older veterans", "url": "https://www.neurology.org/doi/10.1212/WNL.0000000000000616", "year": 2014, "journal": "Neurology", "study_design": "cohort", "design_label": "Cohort", "n_participants": 188764, "effect_size": "16% of veterans with TBI developed dementia vs 10% of those without TBI; adjusted HR 1.57 (95% CI 1.35-1.83)", "pmid": "", "doi": "" }, { "title": "Dementia risk after traumatic brain injury vs nonbrain trauma: the role of age and severity", "url": "https://pubmed.ncbi.nlm.nih.gov/25347255/", "year": 2014, "journal": "JAMA neurology", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 164661, "effect_size": "31.5%; 8.4%; 5.9%", "pmid": "25347255", "doi": "10.1001/jamaneurol.2014.2668" }, { "title": "Sex differences in risk factors for Alzheimer dementia encephalopathy patients", "url": "https://pubmed.ncbi.nlm.nih.gov/40491970/", "year": 2025, "journal": "Frontiers in Dementia", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 128769, "effect_size": "OR = 1.144; OR = 1.606; OR = 1.555", "pmid": "40491970", "doi": "10.3389/frdem.2025.1593788" }, { "title": "Association of Mild Traumatic Brain Injury With and Without Loss of Consciousness With Dementia in US Military Veterans", "url": "https://pubmed.ncbi.nlm.nih.gov/29801145/", "year": 2018, "journal": "JAMA neurology", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 178, "effect_size": "9.3%; 72.5%; 2.6%", "pmid": "29801145", "doi": "10.1001/jamaneurol.2018.0815" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "PREV-13", "group": "prevention", "question": "Education and cognitive reserve", "note": "", "class_label": "", "n_studies": 196, "design_counts": { "systematic_review": 5, "meta_analysis": 12, "rct": 8, "cohort": 42, "case_control": 6, "cross_sectional": 19, "other": 104 }, "design_mix_text": "196 studies: Systematic review 5, Meta-analysis 12, RCT / clinical trial 8, Cohort 42, Case-control 6, Cross-sectional 19, Other / not reported 104", "featured": [ { "title": "Worldwide prevalence of mild cognitive impairment among community dwellers aged 50 years and older: a meta-analysis and systematic review of epidemiology studies", "url": "https://pubmed.ncbi.nlm.nih.gov/35977150/", "year": 2022, "journal": "Age and ageing", "study_design": "systematic review", "design_label": "Systematic review", "n_participants": 242804, "effect_size": "15.56%; 18.03%; 10.03%", "pmid": "35977150", "doi": "10.1093/ageing/afac173" }, { "title": "Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission", "url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf", "year": 2024, "journal": "The Lancet", "study_design": "systematic-review", "design_label": "Systematic review", "n_participants": null, "effect_size": "~45% of dementia cases theoretically attributable to combined modifiable factors; LDL cholesterol ~7% PAF; vision loss ~2% PAF", "pmid": "", "doi": "" }, { "title": "Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study", "url": "https://pubmed.ncbi.nlm.nih.gov/31335910/", "year": 2019, "journal": "PLoS medicine", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 48522, "effect_size": "58.4%", "pmid": "31335910", "doi": "10.1371/journal.pmed.1002853" }, { "title": "Midlife and late‐life population attributable fractions of risk factors for dementia in the United States: The Dementia Risk Prediction Project", "url": "https://pubmed.ncbi.nlm.nih.gov/41559019/", "year": 2026, "journal": "Alzheimer s & Dementia", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 37931, "effect_size": "22.7%; 16.5%; 7.7%", "pmid": "41559019", "doi": "10.1002/alz.71065" }, { "title": "Education, Occupational Complexity, and Incident Dementia: A COSMIC Collaborative Cohort Study", "url": "https://pubmed.ncbi.nlm.nih.gov/34776437/", "year": 2022, "journal": "Journal of Alzheimer's Disease", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 10195, "effect_size": "Education and occupational complexity independently associated with longer dementia-free survival (28% of education effect mediated by occupation)", "pmid": "34776437", "doi": "10.3233/JAD-210627" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "PREV-14", "group": "prevention", "question": "Air pollution (individual-level exposure)", "note": "Only a handful of individual-level studies exist here -- most of this site's air-pollution evidence is at the place level, in the geography section below.", "class_label": "", "n_studies": 26, "design_counts": { "systematic_review": 2, "meta_analysis": 3, "rct": 1, "cohort": 4, "case_control": 0, "cross_sectional": 3, "other": 13 }, "design_mix_text": "26 studies: Systematic review 2, Meta-analysis 3, RCT / clinical trial 1, Cohort 4, Cross-sectional 3, Other / not reported 13", "featured": [ { "title": "Long-term air pollution exposure and incident dementia: a systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/40716448/", "year": 2025, "journal": "Lancet Planetary Health", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": 24030527, "effect_size": "PM2.5 HR 1.08 per 5 ug/m3 (95% CI 1.02-1.14); NO2 HR 1.03 per 10 ug/m3 (1.01-1.05)", "pmid": "40716448", "doi": "10.1016/S2542-5196(25)00118-4" }, { "title": "Population Attributable Fraction of Modifiable Risk Factors for Dementia in Turkey", "url": "https://pubmed.ncbi.nlm.nih.gov/40583126/", "year": 2025, "journal": "Dementia", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": null, "effect_size": "49.9%; 54.2%; 44.3%", "pmid": "40583126", "doi": "10.1177/14713012251357162" }, { "title": "Ambient air pollution and clinical dementia: systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/37019461/", "year": 2023, "journal": "BMJ", "study_design": "meta-analysis", "design_label": "Meta-analysis", "n_participants": null, "effect_size": "PM2.5 HR 1.04 per 2 ug/m3 (95% CI 0.99-1.09) overall; 1.42 (1.00-2.02) with active case ascertainment", "pmid": "37019461", "doi": "10.1136/bmj-2022-071620" }, { "title": "In the context of a deprived neighborhood, does self‐identified race cause dementia?", "url": "https://doi.org/10.1002/alz.066311", "year": 2023, "journal": "Alzheimer s & Dementia", "study_design": "cohort study", "design_label": "Cohort", "n_participants": 2733, "effect_size": "0.9%; 5.2%; OR = 1.61", "pmid": "", "doi": "10.1002/alz.066311" }, { "title": "Traffic-Related Air Pollution and Dementia Incidence in Northern Sweden: A Longitudinal Study", "url": "https://pubmed.ncbi.nlm.nih.gov/26305859/", "year": 2016, "journal": "Environmental health perspectives", "study_design": "prospective cohort", "design_label": "Cohort", "n_participants": 1806, "effect_size": "HR 1.38; HR 1.47; HR = 1.71", "pmid": "26305859", "doi": "10.1289/ehp.1408322" } ], "verdict": "ready", "blocked_by": null, "svg": null, "svg_caption": "", "svg_alt": "", "group_chart_svg": null, "group_chart_alt": "", "group_chart_caption": "", "is_group_first": false }, { "id": "S1", "level": "state", "panel": "panel_state", "exposure": { "name": "pm25_avg_ugm3", "description": "Average annual fine particulate matter (PM2.5) concentration", "unit": "ug/m3", "year": 2023, "source_name": "America's Health Rankings, Air Pollution (source: EPA), 2022-2024 average", "source_url": "https://www.americashealthrankings.org/explore/measures/air", "caveat": "Reported as a 2022-2024 multi-year average by the source; year recorded as the midpoint (2023)." }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Do states with higher fine-particulate air pollution carry higher Alzheimer's mortality rates?", "rationale": "PM2.5 is a live candidate environmental risk factor. State-level pollution averages vary enough to give the comparison range, and the mortality outcome is complete at this level.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Recorded-cause mortality tracks diagnostic and coding capacity, so Test 1 matters most here: correlate the outcome against income and physician supply first. If mortality tracks those hard, the pollution correlation is partly measuring health-system intensity.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "group_title": "Geography (a weaker, separate class of evidence)", "group_intro": "Everything below this line compares PLACES, not people: do states, counties or countries with more of an exposure also show more of an outcome. A correlation between places is not a statement about a person -- it cannot tell you that living somewhere changes your own risk, only that two averages move together. It is also frequently a correlation about measurement rather than disease: under-diagnosis and genuinely lower disease look identical in this kind of data, because both produce a lower recorded rate. These 43 questions are kept, unchanged, at the bottom of this page because the panels behind them are real and the arithmetic is real -- but they are a weaker form of evidence than anything above, and should be read that way.", "is_group_first": true }, { "id": "S2", "level": "state", "panel": "panel_state", "exposure": { "name": "pct_hearing_loss", "description": "Percent of adults with any hearing loss", "unit": "percent", "year": 2016, "source_name": "CDC/NCHS, Any Hearing Loss by State, National Health Interview Survey 2014-2016 (Blackwell & Norris)", "source_url": "https://www.cdc.gov/nchs/data/health_policy/hearing_loss_table_SEs.pdf", "caveat": "Oldest data-year in the risk-factor block (2014-2016 pooled); no newer full 51-state BRFSS hearing-loss table was locatable in this session." }, "outcome": { "name": "alz_prevalence_65plus_pct", "description": "Estimated percentage of the population age 65+ living with Alzheimer's dementia", "unit": "percent", "year": 2020, "source_name": "Alzheimer's Association 2025 Alzheimer's Disease Facts and Figures, Table 5 (data from Dhana et al., state/county prevalence model)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Modeled estimate based on 2020 age/sex/race population distributions, not a direct case count or registry; published in the 2025 F&F report." }, "question": "Is state-level hearing-loss prevalence associated with Alzheimer's prevalence?", "rationale": "Hearing loss is one of the best-supported modifiable risk factors in the Lancet Commission work, so it is the strongest prior for a positive finding - which is exactly why a null would be informative.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Prevalence is modelled from an age structure, so it will track pct_65plus almost by construction. Adjust for age structure before reading the exposure; if the association vanishes, it was demography.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S3", "level": "state", "panel": "panel_state", "exposure": { "name": "pct_diabetes", "description": "Percent of adults with diagnosed diabetes", "unit": "percent", "year": 2024, "source_name": "KFF State Health Facts, Adults with Diagnosed Diabetes (CDC BRFSS)", "source_url": "https://www.kff.org/other/state-indicator/adults-with-diabetes/", "caveat": "Tennessee blank: TN did not submit sufficient 2024 BRFSS sample for KFF to report a value." }, "outcome": { "name": "alz_prevalence_65plus_pct", "description": "Estimated percentage of the population age 65+ living with Alzheimer's dementia", "unit": "percent", "year": 2020, "source_name": "Alzheimer's Association 2025 Alzheimer's Disease Facts and Figures, Table 5 (data from Dhana et al., state/county prevalence model)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Modeled estimate based on 2020 age/sex/race population distributions, not a direct case count or registry; published in the 2025 F&F report." }, "question": "Is state-level diabetes prevalence associated with Alzheimer's prevalence?", "rationale": "Midlife diabetes is an established risk factor. Both columns are complete, making this the cleanest first test of the whole panel.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Diabetes, obesity, inactivity and hypertension are mutually correlated, so a single-exposure model will not isolate any one of them. Run the exposures together and report which survive; a lone 'significant' predictor among four collinear ones is not a finding.", "group": "geography", "n_units": 51, "exposure_coverage": 98.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S4", "level": "state", "panel": "panel_state", "exposure": { "name": "pct_bachelors_plus", "description": "Percent of population 25+ with a bachelor's degree or higher", "unit": "percent", "year": 2023, "source_name": "U.S. Census Bureau, ACS 2023 1-Year Estimates, GCT1502", "source_url": "https://www2.census.gov/programs-surveys/acs/data/2023/1_year_geographic_comparison_tables/", "caveat": "" }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Do more-educated states record higher Alzheimer's mortality?", "rationale": "A sign flip is the highest-value signal in an ecological analysis. Education is protective at the individual level, so if it correlates POSITIVELY with recorded mortality at state level that is almost certainly a diagnostic-capacity artifact - and demonstrating it is a real result.", "design": "Ecological cross-section, 51 states and DC.", "triage": "This is the designed artifact test. Expect a positive sign. Run the full four-step triage: Test 1 against wealth, Test 2 stratified into income quartiles, Test 3 against the modelled prevalence outcome, Test 4 partial on age and income together. Publishing the triage, not the coefficient, is the deliverable.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S5", "level": "state", "panel": "panel_state", "exposure": { "name": "neurologists_per_100k", "description": "Neurologists per 100,000 population", "unit": "rate per 100k", "year": 2024, "source_name": "American Academy of Neurology, 2025 Member Demographics Report, Table 10b", "source_url": "https://www.aan.com/siteassets/home-page/conferences-and-community/member-engagement/learn-about-aan-committees/strategic-planning-committee/25-member-demographics-report.pdf", "caveat": "Based on AAN membership records, not a full practitioner census; likely a modest, roughly uniform undercount of true neurologist supply." }, "outcome": { "name": "alz_count_65plus", "description": "Estimated number of people age 65+ living with Alzheimer's dementia", "unit": "count", "year": 2020, "source_name": "Alzheimer's Association 2025 Alzheimer's Disease Facts and Figures, Table 5", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report gives this in thousands (1 decimal); value here is that figure x1000, rounded to nearest integer. Same modeled-estimate caveat as alz_prevalence_65plus_pct." }, "question": "Do states with more neurologists per capita identify more Alzheimer's cases?", "rationale": "A direct measure of diagnostic supply against a case count. It quantifies how much of the geography of Alzheimer's is a geography of who gets diagnosed.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Counts are denominators-inflated: a large state has more cases for reasons unrelated to supply. Model the RATE not the count, or include population as an offset - otherwise the correlation restates population.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S6", "level": "state", "panel": "panel_state", "exposure": { "name": "geriatricians_count", "description": "Number of board-certified geriatricians practicing in the state (bonus column, not in required spec)", "unit": "count", "year": 2021, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 14, citing American Geriatrics Society", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "2021 is the most recent year available in the source report; included as a bonus workforce-supply column alongside primary_care_physicians_per_100k and neurologists_per_100k." }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Is geriatrician supply associated with Alzheimer's mortality at state level?", "rationale": "Tests whether specialist workforce tracks recorded outcomes, the same confound structure as S5 but with a different workforce series, so the two can be compared.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Geriatrician counts are raw counts, so they track state size. Rate-adjust first. If S5 and S6 disagree in sign, that disagreement is itself the finding about how unstable workforce measures are at this level.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S7", "level": "state", "panel": "panel_state", "exposure": { "name": "medicaid_ltss_spend_per_capita", "description": "Medicaid dementia spending per capita (total state population)", "unit": "usd per capita", "year": 2025, "source_name": "Derived by this project: medicaid_dementia_spend_total_usd / pop_total", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Computed value, not published directly. Numerator is 2025-projected dementia-specific Medicaid spend (Table 22); denominator is 2024 total population (Census), so there is a 1-year vintage mismatch between numerator and denominator. Also note this is total dementia-related Medicaid spend, not specifically LTSS/long-term-services-and-supports spend, which was not separately available by state." }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Does higher per-capita long-term-services spending associate with Alzheimer's mortality?", "rationale": "An economics-versus-outcome question. Spending should track need, so a positive correlation is expected and mostly uninformative; a negative one would be the interesting case.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Spending reflects need AND wealth AND policy, all at once. Partial on median income and pct_65plus; if the coefficient grows more extreme after adjusting, it is behaving like conditioning on a collider rather than like a risk factor.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S8", "level": "state", "panel": "panel_state", "exposure": { "name": "alz_state_plan", "description": "Whether the state has a published state Alzheimer's/dementia plan (1=yes, 0=no)", "unit": "count (binary 0/1)", "year": 2024, "source_name": "Alzheimer's Impact Movement, State Alzheimer's Disease Plans", "source_url": "https://portal.alzimpact.org/storage/resources/media-items/StateAlzheimersDiseasePlans.pdf", "caveat": "Source states that every state, DC, and Puerto Rico has published a plan since 2007; all 51 rows are therefore 1. Plan VINTAGE varies widely by state (some updated 2020-2024, some older) -- presence of a plan does not imply currency." }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Do states with a published Alzheimer's state plan have different mortality?", "rationale": "A policy-adoption question with a binary exposure. Any association is almost certainly reverse-causal - states write plans because burden is high - which makes it a clean teaching case for why the design cannot support a causal reading.", "design": "Ecological cross-section, 51 states and DC. Binary exposure.", "triage": "Reverse causality is the default explanation. Do not present the sign as an effect of the plan. Treat it as descriptive only, and say so on the card.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S9", "level": "state", "panel": "panel_state", "exposure": { "name": "pct_rural", "description": "Percent of state population classified as rural", "unit": "percent", "year": 2023, "source_name": "America's Health Rankings, Rural Population (Census ACS 1-Year)", "source_url": "https://www.americashealthrankings.org/explore/measures/pct_rural_b", "caveat": "2023 ACS-based estimate, not the 2020 decennial Census urban/rural classification." }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Is rurality associated with Alzheimer's mortality?", "rationale": "Rurality plausibly raises both risk and the difficulty of being diagnosed, so it is a candidate for a genuinely informative positive association.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Rural states are older and poorer on average, so age and income adjustment is required before any reading. Report unadjusted and adjusted side by side.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S10", "level": "state", "panel": "panel_state", "exposure": { "name": "pct_uninsured", "description": "Percent of total population without health insurance", "unit": "percent", "year": 2024, "source_name": "KFF State Health Facts, Health Insurance Coverage of the Total Population (ACS-based)", "source_url": "https://www.kff.org/state-health-policy-data/state-indicator/total-population/", "caveat": "ACS-based rather than BRFSS-based, so Tennessee is populated here even though it is blank in several BRFSS-sourced columns." }, "outcome": { "name": "alz_prevalence_65plus_pct", "description": "Estimated percentage of the population age 65+ living with Alzheimer's dementia", "unit": "percent", "year": 2020, "source_name": "Alzheimer's Association 2025 Alzheimer's Disease Facts and Figures, Table 5 (data from Dhana et al., state/county prevalence model)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Modeled estimate based on 2020 age/sex/race population distributions, not a direct case count or registry; published in the 2025 F&F report." }, "question": "Does insurance coverage track Alzheimer's prevalence across states?", "rationale": "Access-to-care proxy against a prevalence estimate. Most people with Alzheimer's are Medicare-eligible, so a strong association would be suspicious rather than informative.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Expect weak. A strong result here is a signal that both columns are tracking the same underlying state-level development index, i.e. a measurement artifact.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S11", "level": "state", "panel": "panel_state", "exposure": { "name": "unpaid_caregiver_hours_millions", "description": "Hours of unpaid care provided by family/other caregivers", "unit": "count (millions of hours)", "year": 2024, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 10", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "US total 19,161 million hours (~19.2 billion)." }, "outcome": { "name": "alz_count_65plus", "description": "Estimated number of people age 65+ living with Alzheimer's dementia", "unit": "count", "year": 2020, "source_name": "Alzheimer's Association 2025 Alzheimer's Disease Facts and Figures, Table 5", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report gives this in thousands (1 decimal); value here is that figure x1000, rounded to nearest integer. Same modeled-estimate caveat as alz_prevalence_65plus_pct." }, "question": "Do states with more unpaid caregiving hours have more Alzheimer's cases?", "rationale": "Both are burden measures. Useful as a consistency check between an independent caregiver-burden series and the case count.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Both columns scale with state population. Normalise both per capita or the correlation is a population correlation wearing a caregiving label.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "S12", "level": "state", "panel": "panel_state", "exposure": { "name": "pct_depression", "description": "Percent of adults ever told they have a depressive disorder", "unit": "percent", "year": 2024, "source_name": "America's Health Rankings, Depression (CDC BRFSS)", "source_url": "https://www.americashealthrankings.org/explore/measures/Depression_a", "caveat": "Tennessee value is 2023 (27.3%) because the 2024 BRFSS row for TN was marked unavailable nationally; all other states are 2024." }, "outcome": { "name": "alz_prevalence_65plus_pct", "description": "Estimated percentage of the population age 65+ living with Alzheimer's dementia", "unit": "percent", "year": 2020, "source_name": "Alzheimer's Association 2025 Alzheimer's Disease Facts and Figures, Table 5 (data from Dhana et al., state/county prevalence model)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Modeled estimate based on 2020 age/sex/race population distributions, not a direct case count or registry; published in the 2025 F&F report." }, "question": "Is state-level depression prevalence associated with Alzheimer's prevalence?", "rationale": "Depression is both a risk factor for and a consequence of dementia, so direction is unresolvable at group level - which makes the card honest about what it cannot show.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Cannot be interpreted directionally by construction. Present as descriptive association only. Self-report depression and modelled prevalence may share survey structure, inflating the coefficient.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "B1", "level": "state", "panel": "panel_state", "exposure": { "name": "pct_race_black", "description": "Percent of population Black or African American alone", "unit": "percent", "year": 2023, "source_name": "U.S. Census Bureau, ACS 2023 1-Year Estimates, GCT0202", "source_url": "https://www2.census.gov/programs-surveys/acs/data/2023/1_year_geographic_comparison_tables/", "caveat": "" }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Is the Black share of a state's population associated with its Alzheimer's mortality rate?", "rationale": "Individual-level studies consistently find higher dementia incidence and prevalence among Black Americans than white Americans. This tests whether that documented disparity is visible in aggregate state-level mortality data, which no study in this catalogue has yet examined.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Racial composition correlates strongly with state median income and poverty rate, and recorded mortality tracks diagnostic/coding capacity (see S4). Control for median_household_income before reading any coefficient - otherwise the correlation may restate income, not race.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "B2", "level": "state", "panel": "panel_state", "exposure": { "name": "pct_race_hispanic", "description": "Percent of population Hispanic or Latino (any race)", "unit": "percent", "year": 2024, "source_name": "KFF State Health Facts, Distribution by Race/Ethnicity (ACS 1-Year Estimates)", "source_url": "https://www.kff.org/other/state-indicator/distribution-by-raceethnicity/", "caveat": "" }, "outcome": { "name": "alz_prevalence_65plus_pct", "description": "Estimated percentage of the population age 65+ living with Alzheimer's dementia", "unit": "percent", "year": 2020, "source_name": "Alzheimer's Association 2025 Alzheimer's Disease Facts and Figures, Table 5 (data from Dhana et al., state/county prevalence model)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Modeled estimate based on 2020 age/sex/race population distributions, not a direct case count or registry; published in the 2025 F&F report." }, "question": "Is the Hispanic share of a state's population associated with modelled Alzheimer's prevalence among its 65+ residents?", "rationale": "Hispanic Americans are also documented to carry elevated individual-level dementia risk relative to non-Hispanic white Americans, making this the natural companion to B1 with a different disparity population.", "design": "Ecological cross-section, 51 states and DC.", "triage": "States with a larger Hispanic share tend to have a younger overall population, and alz_prevalence_65plus_pct is itself modelled from age structure (see S2). Control for pct_65plus - a null or negative result could simply be demography, not risk.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "B3", "level": "state", "panel": "panel_state", "exposure": { "name": "gini", "description": "Gini index of income inequality (0=perfect equality, 1=perfect inequality)", "unit": "index (0-1)", "year": 2019, "source_name": "Wikipedia 'List of U.S. states and territories by income inequality', citing Census ACS table B19083", "source_url": "https://en.wikipedia.org/wiki/List_of_U.S._states_and_territories_by_income_inequality", "caveat": "Oldest-vintage column in the panel (2019). A 2022/2023 Census B19083 pull requires an API key that was unavailable in this session; direct data.census.gov table B19083 should be re-pulled for a fresher value if precision matters." }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Is state-level income inequality associated with Alzheimer's mortality, independent of income level?", "rationale": "Every income-related question so far in this catalogue uses income LEVEL (median_household_income) or poverty rate. Gini measures the distribution of income within a state, a genuinely different construct that has not been tested against any outcome here.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Gini and median_household_income are not the same thing but both move with a state's general development level. Control for median_household_income so the coefficient reflects inequality specifically, not wealth.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "B4", "level": "state", "panel": "panel_state", "exposure": { "name": "pct_below_poverty", "description": "Percent of population below the poverty line", "unit": "percent", "year": 2023, "source_name": "U.S. Census Bureau, ACS 2023 1-Year Estimates, GCT1701", "source_url": "https://www2.census.gov/programs-surveys/acs/data/2023/1_year_geographic_comparison_tables/", "caveat": "" }, "outcome": { "name": "alz_prevalence_65plus_pct", "description": "Estimated percentage of the population age 65+ living with Alzheimer's dementia", "unit": "percent", "year": 2020, "source_name": "Alzheimer's Association 2025 Alzheimer's Disease Facts and Figures, Table 5 (data from Dhana et al., state/county prevalence model)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Modeled estimate based on 2020 age/sex/race population distributions, not a direct case count or registry; published in the 2025 F&F report." }, "question": "Is the state poverty rate associated with modelled Alzheimer's prevalence among 65+ residents?", "rationale": "Poverty is a distinct construct from income inequality (B3) and from median income, and has an independent evidence base linking childhood and midlife socioeconomic disadvantage to dementia risk.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Prevalence is modelled from age structure (see S2), and poorer states are not uniformly older or younger. Control for pct_65plus before treating any association as a poverty effect rather than an artifact of age composition.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "B5", "level": "state", "panel": "panel_state", "exposure": { "name": "primary_care_physicians_per_100k", "description": "Primary care providers per 100,000 population", "unit": "rate per 100k", "year": 2025, "source_name": "America's Health Rankings, Primary Care Providers (CMS National Plan and Provider Enumeration System)", "source_url": "https://www.americashealthrankings.org/explore/measures/PCP_NPPES", "caveat": "Includes nurse practitioners and physician assistants alongside physicians, so this is broader than a 'physicians only' count." }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Do states with more primary-care capacity record higher Alzheimer's mortality?", "rationale": "S5 and S6 test specialist supply (neurologists, geriatricians) against case counts. Primary care is the front door where most cognitive concerns are first raised, and this column has not yet been used anywhere in the catalogue.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Primary-care density is much lower in rural areas, which also have documented under-diagnosis of dementia. Control for pct_rural before reading the coefficient as a supply effect.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "B6", "level": "state", "panel": "panel_state", "exposure": { "name": "nursing_home_beds_per_1000", "description": "Nursing home beds per 1,000 population age 65+", "unit": "rate per 1000 (65+ population)", "year": 2026, "source_name": "Becker's Hospital Review, States ranked by nursing home beds per capita (May 2026), using Census population + KFF CNF bed data", "source_url": "https://www.beckershospitalreview.com/post-acute/states-ranked-by-nursing-home-beds-per-capita/", "caveat": "IMPORTANT: denominator is population 65+, not total population -- NOT directly comparable to hospital_beds_per_1000, which is per 1,000 TOTAL population." }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Is nursing-home bed capacity associated with Alzheimer's mortality across states?", "rationale": "A1-A6 use nursing_home_beds_per_1000 only as a companion to a caregiving survey measure (A2). This pairs it directly against the hard mortality outcome: institutionalized patients are more likely to have care contact that produces an Alzheimer's-coded death certificate, so bed supply may track recorded mortality independent of true disease burden.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Nursing-home bed rates are calculated per 1,000 population 65+ (see column caveat), and the oldest-old drive both nursing-home demand and mortality risk directly. Control for pct_85plus before interpreting.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "C1", "level": "county", "panel": "panel_county", "exposure": { "name": "pm25_avg_ugm3", "description": "Average daily fine particulate matter (PM2.5) concentration", "unit": "micrograms per cubic meter (ug/m3)", "year": "~2021 (CDC/EPA Environmental Public Health Tracking vintage embedded in CHR 2024)", "source_name": "County Health Rankings & Roadmaps (Univ. of Wisconsin Population Health Institute), 2024 release", "source_url": "https://www.countyhealthrankings.org/health-data/methodology-and-sources/rankings-data-documentation", "caveat": "CHR pass-through of CDC/EPA Air Quality System modelled daily PM2.5 concentration estimates -- itself a MODELLED (not directly monitored-everywhere) estimate produced by CDC's Environmental Public Health Tracking Network, since ground monitors do not exist in every county." }, "outcome": { "name": "norc_dementia_mortality_rate_2020", "description": "norc_mort_cnt_2020 / norc_prev_cnt_2020 * 100 -- share of diagnosed prevalent dementia cases who died in 2020 (a case-fatality rate among the diagnosed population)", "unit": "percent (0-100)", "year": "2020", "source_name": "Derived from NORC Dementia DataHub counts per the DataHub's own published rate formula (mortality and COVID measures are divided by prev_cnt, not bene_cnt, per the codebook)", "source_url": "https://www.dementiadatahub.org", "caveat": "IMPORTANT: this is NOT a population mortality rate per 100,000 residents and is NOT comparable to the panel's own (NOT SOURCED) dementia_mortality_per_100k column, despite both being 'dementia mortality' -- it is the percent of already-diagnosed prevalent cases who died that year, i.e. a case-fatality rate, per the DataHub's own denominator guidance. Blank whenever mort_cnt or prev_cnt is suppressed." }, "question": "Is county-level PM2.5 associated with the share of diagnosed dementia patients who died in 2020?", "rationale": "The finest geographic grain the site aims for, and the question the state-level S1 cannot answer because state pollution averages hide within-state variation.", "design": "Ecological cross-section, ~3,100 counties.", "triage": "County mortality is suppressed or unstable in small counties, so any result is dominated by the largest places unless weighted. Weight by population and report the unweighted version beside it. NOTE: the outcome is NORC's case-fatality rate among already-diagnosed prevalent cases (mort_cnt/prev_cnt), not a population-wide per-100k death rate -- read it as 'how deadly is diagnosed dementia here', not as a mortality-burden measure.", "group": "geography", "n_units": 3143, "exposure_coverage": 99.1, "exposure_exists": true, "outcome_coverage": 95.6, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "C2", "level": "county", "panel": "panel_county", "exposure": { "name": "social_association_index", "description": "Number of membership associations (civic, religious, business, political, labor, etc.) per 10,000 population", "unit": "count per 10,000 population", "year": "~2022 (County Business Patterns vintage embedded in CHR 2024)", "source_name": "County Health Rankings & Roadmaps (Univ. of Wisconsin Population Health Institute), 2024 release", "source_url": "https://www.countyhealthrankings.org/health-data/methodology-and-sources/rankings-data-documentation", "caveat": "CHR pass-through of Census County Business Patterns. Already expressed per-10,000; no further conversion applied." }, "outcome": { "name": "norc_dementia_prevalence_rate_2020", "description": "norc_prev_cnt_2020 / norc_bene_cnt_2020 * 100 -- diagnosed dementia prevalence rate among all-age Medicare beneficiaries", "unit": "percent (0-100)", "year": "2020", "source_name": "Derived from NORC Dementia DataHub counts per the DataHub's own published rate formula (dementiadatahub.org/resources/outcome-measures.html)", "source_url": "https://www.dementiadatahub.org", "caveat": "Blank whenever prev_cnt or bene_cnt is suppressed -- never computed from an imputed numerator or denominator. Denominator is ALL-AGE Medicare beneficiaries (includes under-65 disability/ESRD beneficiaries), not restricted to 65+, so this is NOT directly comparable to the panel's own alz_prevalence_pct_65plus column (which remains NOT SOURCED and untouched) despite the similar name." }, "question": "Is county social association density associated with diagnosed dementia prevalence?", "rationale": "Social isolation is a Lancet risk factor and this index is a genuinely local measure, which is why county rather than state resolution is worth having.", "design": "Ecological cross-section, ~3,100 counties.", "triage": "Both are derived from Community / CDC Census series, so shared construction can inflate the coefficient. Check whether the two share a source vintage before interpreting. NOTE: the outcome's denominator is all-age Medicare beneficiaries (not restricted to 65+), and it measures diagnosed claims-based prevalence, not a modelled disease-prevalence estimate -- diagnosis rates vary by place for identical underlying symptoms.", "group": "geography", "n_units": 3143, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 98.8, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "C3", "level": "county", "panel": "panel_county", "exposure": { "name": "pct_living_alone_65plus", "description": "Percent of the 65+ population living alone", "unit": "percent (0-100)", "year": "2020-2024", "source_name": "US Census Bureau, American Community Survey 5-Year Estimates 2020-2024 (detailed tables), retrieved via the Census Reporter API (a non-key-gated public proxy of the official Census Bureau ACS API)", "source_url": "https://www.census.gov/data/developers/data-sets/acs-5year.html", "caveat": "ACS 5-year estimates are themselves modelled/smoothed over a 5-year rolling window (2020-2024), not a single-year census count; small counties carry wide margins of error not included in this file. Connecticut's 8 legacy counties (FIPS 09001-09015) have no data here because the Census Bureau retired those FIPS codes in favor of 9 new Connecticut planning regions for the 2020-2024 vintage -- see README. From table B09021 (population 65+ 'lives alone' living-arrangement category / total population 65+ in that table's universe)." }, "outcome": { "name": "norc_prev_cnt_2020", "description": "Count of Medicare beneficiaries with prevalent diagnosed AD/ADRD in 2020, county total, broadest NORC case definition (DEMENTIACAT blank = 'All Determinations' = Highly likely + Likely + Possible combined)", "unit": "count (persons)", "year": "2020", "source_name": "NORC Dementia DataHub (NORC at the University of Chicago), 2020 Public Use File", "source_url": "https://www.dementiadatahub.org", "caveat": "DIAGNOSED cases identified from Medicare claims, NOT a modelled disease-prevalence estimate -- diagnosis rates for identical underlying symptoms vary by place, so a county with a low count/rate may under-diagnose rather than have less disease. This is a distinct measurement from the panel's own alz_count_estimate column (which remains NOT SOURCED and untouched by this join). Blank where suppressed (true value < 11); blank is NOT zero. See data/county_dementia_outcomes_meta.json for full case-definition and suppression methodology." }, "question": "Does living alone among over-65s associate with the county's diagnosed dementia case count?", "rationale": "Living alone is a practical care-planning variable, and county is the level at which services are actually planned.", "design": "Ecological cross-section, ~3,100 counties.", "triage": "This is a raw count (not a rate), so it scales mechanically with county population and age structure. Adjust for age structure (pct_65plus) or the result is largely arithmetic.", "group": "geography", "n_units": 3143, "exposure_coverage": 99.7, "exposure_exists": true, "outcome_coverage": 98.8, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "C4", "level": "county", "panel": "panel_county", "exposure": { "name": "primary_care_physicians_per_100k", "description": "Primary care physicians per 100,000 population", "unit": "rate per 100,000", "year": "~2022 (Area Health Resources Files vintage embedded in CHR 2024)", "source_name": "County Health Rankings & Roadmaps (Univ. of Wisconsin Population Health Institute), 2024 release", "source_url": "https://www.countyhealthrankings.org/health-data/methodology-and-sources/rankings-data-documentation", "caveat": "CHR pass-through of HRSA Area Health Resources Files; computed here as CHR's population-to-provider ratio raw value inverted and rescaled to per-100k." }, "outcome": { "name": "norc_dementia_mortality_rate_2020", "description": "norc_mort_cnt_2020 / norc_prev_cnt_2020 * 100 -- share of diagnosed prevalent dementia cases who died in 2020 (a case-fatality rate among the diagnosed population)", "unit": "percent (0-100)", "year": "2020", "source_name": "Derived from NORC Dementia DataHub counts per the DataHub's own published rate formula (mortality and COVID measures are divided by prev_cnt, not bene_cnt, per the codebook)", "source_url": "https://www.dementiadatahub.org", "caveat": "IMPORTANT: this is NOT a population mortality rate per 100,000 residents and is NOT comparable to the panel's own (NOT SOURCED) dementia_mortality_per_100k column, despite both being 'dementia mortality' -- it is the percent of already-diagnosed prevalent cases who died that year, i.e. a case-fatality rate, per the DataHub's own denominator guidance. Blank whenever mort_cnt or prev_cnt is suppressed." }, "question": "Do counties with more primary care have a higher case-fatality rate among diagnosed dementia patients?", "rationale": "The county-scale version of S5's diagnostic-supply question, with far more power and far more noise.", "design": "Ecological cross-section, ~3,100 counties.", "triage": "Small-county rates rest on a handful of deaths. Drop counties below a population floor and report how many that removed, rather than letting a 40-person county dominate. NOTE: outcome is case-fatality among diagnosed cases (mort_cnt/prev_cnt), not a population mortality rate -- more primary care could mechanically raise this by diagnosing milder/earlier cases that dilute or inflate the denominator, so read with care.", "group": "geography", "n_units": 3143, "exposure_coverage": 95.0, "exposure_exists": true, "outcome_coverage": 95.6, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "D1", "level": "county", "panel": "panel_county", "exposure": { "name": "pct_black", "description": "Percent of population that is Black or African American alone, Not Hispanic or Latino", "unit": "percent (0-100)", "year": "2020-2024", "source_name": "US Census Bureau, American Community Survey 5-Year Estimates 2020-2024 (detailed tables), retrieved via the Census Reporter API (a non-key-gated public proxy of the official Census Bureau ACS API)", "source_url": "https://www.census.gov/data/developers/data-sets/acs-5year.html", "caveat": "ACS 5-year estimates are themselves modelled/smoothed over a 5-year rolling window (2020-2024), not a single-year census count; small counties carry wide margins of error not included in this file. Connecticut's 8 legacy counties (FIPS 09001-09015) have no data here because the Census Bureau retired those FIPS codes in favor of 9 new Connecticut planning regions for the 2020-2024 vintage -- see README. From table B03002. Excludes Hispanic Black residents (counted under pct_hispanic instead) -- this is the standard non-Hispanic race breakdown, not 'Black alone regardless of ethnicity.'" }, "outcome": { "name": "norc_dementia_prevalence_rate_2020", "description": "norc_prev_cnt_2020 / norc_bene_cnt_2020 * 100 -- diagnosed dementia prevalence rate among all-age Medicare beneficiaries", "unit": "percent (0-100)", "year": "2020", "source_name": "Derived from NORC Dementia DataHub counts per the DataHub's own published rate formula (dementiadatahub.org/resources/outcome-measures.html)", "source_url": "https://www.dementiadatahub.org", "caveat": "Blank whenever prev_cnt or bene_cnt is suppressed -- never computed from an imputed numerator or denominator. Denominator is ALL-AGE Medicare beneficiaries (includes under-65 disability/ESRD beneficiaries), not restricted to 65+, so this is NOT directly comparable to the panel's own alz_prevalence_pct_65plus column (which remains NOT SOURCED and untouched) despite the similar name." }, "question": "Is the Black share of a county's population associated with diagnosed dementia prevalence?", "rationale": "The county-level version of B1, at the finer grain where within-state racial and economic segregation is visible rather than averaged away.", "design": "Ecological cross-section, ~3,100 counties.", "triage": "Same confound as B1: county racial composition correlates with county median income. Control for median_household_income before reading any coefficient. NOTE: diagnosed prevalence in Medicare claims can itself be lower where diagnostic access is lower, which correlates with the same demographic and income patterns -- a null or negative result here may reflect under-diagnosis, not lower true prevalence.", "group": "geography", "n_units": 3143, "exposure_coverage": 99.7, "exposure_exists": true, "outcome_coverage": 98.8, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "D2", "level": "county", "panel": "panel_county", "exposure": { "name": "pct_below_poverty", "description": "Percent of all people (all ages) with income in the past 12 months below the poverty level", "unit": "percent (0-100)", "year": "2020-2024", "source_name": "US Census Bureau, American Community Survey 5-Year Estimates 2020-2024 (detailed tables), retrieved via the Census Reporter API (a non-key-gated public proxy of the official Census Bureau ACS API)", "source_url": "https://www.census.gov/data/developers/data-sets/acs-5year.html", "caveat": "ACS 5-year estimates are themselves modelled/smoothed over a 5-year rolling window (2020-2024), not a single-year census count; small counties carry wide margins of error not included in this file. Connecticut's 8 legacy counties (FIPS 09001-09015) have no data here because the Census Bureau retired those FIPS codes in favor of 9 new Connecticut planning regions for the 2020-2024 vintage -- see README. From table B17001 (total population poverty status, not just children). Differs from CHR's 'Children in Poverty' measure, which was NOT used here." }, "outcome": { "name": "norc_dementia_mortality_rate_2020", "description": "norc_mort_cnt_2020 / norc_prev_cnt_2020 * 100 -- share of diagnosed prevalent dementia cases who died in 2020 (a case-fatality rate among the diagnosed population)", "unit": "percent (0-100)", "year": "2020", "source_name": "Derived from NORC Dementia DataHub counts per the DataHub's own published rate formula (mortality and COVID measures are divided by prev_cnt, not bene_cnt, per the codebook)", "source_url": "https://www.dementiadatahub.org", "caveat": "IMPORTANT: this is NOT a population mortality rate per 100,000 residents and is NOT comparable to the panel's own (NOT SOURCED) dementia_mortality_per_100k column, despite both being 'dementia mortality' -- it is the percent of already-diagnosed prevalent cases who died that year, i.e. a case-fatality rate, per the DataHub's own denominator guidance. Blank whenever mort_cnt or prev_cnt is suppressed." }, "question": "Is county poverty rate associated with the case-fatality rate among diagnosed dementia patients?", "rationale": "The county-level version of B4, using mortality rather than prevalence as the outcome and testing whether poverty's association (if any) is visible at a grain state averages could hide.", "design": "Ecological cross-section, ~3,100 counties.", "triage": "Poorer counties tend to have less healthcare access, which could suppress recorded mortality (fewer death-certificate diagnoses) even if true burden is higher. Control for pct_uninsured before reading the sign of any coefficient. NOTE: outcome is case-fatality among already-diagnosed cases (mort_cnt/prev_cnt), not a population mortality rate.", "group": "geography", "n_units": 3143, "exposure_coverage": 99.7, "exposure_exists": true, "outcome_coverage": 95.6, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "I1", "level": "country", "panel": "panel_country", "exposure": { "name": "gdp_per_capita_usd", "description": "GDP per capita, current US$", "unit": "current US$", "year": "latest per country, 2011-2025", "source_name": "World Bank", "source_url": "https://api.worldbank.org/v2/country/all/indicator/NY.GDP.PCAP.CD?format=json&per_page=20000", "caveat": "Current (nominal) USD, not PPP-adjusted — cross-country comparisons of purchasing power will understate low-income-country living standards relative to a PPP series. A few countries (e.g. Venezuela) are stuck at an older year because WB suspended recent estimates." }, "outcome": { "name": "dementia_deaths_per_100k_age_std", "description": "Death rate from Alzheimer's disease and other dementias, both sexes", "unit": "deaths per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://ourworldindata.org/grapher/death-rate-from-alzheimers-other-dementias-ghe ; raw values via https://api.ourworldindata.org/v1/indicators/969491.data.json", "caveat": "IMPORTANT: despite the column name (kept for schema consistency with the task spec), this is WHO GHE's crude, all-ages death rate ('age_group_allages' in the source's own variable short-name), NOT age-standardized. It is therefore NOT safe to compare directly across countries with very different age structures without also controlling for pct_65plus/median_age in your regression — an older country will show a mechanically higher crude dementia death rate even with identical age-specific risk. True age-standardized GBD dementia mortality exists but sits behind the same IHME access wall described above." }, "question": "Does national income correlate with age-standardised dementia mortality?", "rationale": "The clearest test of whether the global geography of dementia mortality is a geography of measurement. Rich countries record more dementia deaths, and this quantifies by how much.", "design": "Ecological cross-section, 217 countries.", "triage": "This is expected to be a measurement result, not a risk result. Use it as the reference correlation that other international findings must beat before being taken seriously.", "group": "geography", "n_units": 217, "exposure_coverage": 98.6, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "I2", "level": "country", "panel": "panel_country", "exposure": { "name": "pct_diabetes", "description": "Prevalence of diabetes among adults, age-standardized", "unit": "% of adults", "year": "latest per country, mostly 2022", "source_name": "WHO Global Health Observatory (NCD-RisC)", "source_url": "https://ghoapi.azureedge.net/api/NCD_DIABETES_PREVALENCE_AGESTD", "caveat": "Both sexes, age-standardized, NCD-RisC modeled estimate (survey data smoothed/interpolated across countries and years, not a raw national survey figure for every country)." }, "outcome": { "name": "dementia_daly_per_100k", "description": "Disability-adjusted life years (DALYs) from Alzheimer's disease and other dementias, both sexes, all ages", "unit": "DALYs per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://api.ourworldindata.org/v1/indicators/969489.data.json", "caveat": "Modelled estimate (see dementia_deaths_total caveat). Crude/all-ages, not age-standardized. DALYs = years of life lost to premature death (YLL) + years lived with disability (YLD); for dementia the YLD component dominates and rests on modelled disease-severity distributions, adding another layer of estimation uncertainty beyond the mortality data alone." }, "question": "Is national diabetes prevalence associated with dementia DALYs?", "rationale": "Metabolic risk against a modelled disease-burden outcome, across a wide range of national contexts.", "design": "Ecological cross-section, 217 countries.", "triage": "DALYs are modelled by IHME from covariate inputs; diabetes prevalence is plausibly among those covariates. Check IHME's own covariate documentation before presenting this as independent evidence - a modelled outcome sharing an input with the exposure is not a test.", "group": "geography", "n_units": 217, "exposure_coverage": 90.3, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "I3", "level": "country", "panel": "panel_country", "exposure": { "name": "health_spend_per_capita_usd", "description": "Current health expenditure per capita, US$", "unit": "current US$", "year": "latest per country, 2020-2024", "source_name": "World Bank / WHO GHED", "source_url": "https://api.worldbank.org/v2/country/all/indicator/SH.XPD.CHEX.PC.CD?format=json&per_page=20000", "caveat": "Same lineage note as health_spend_pct_gdp." }, "outcome": { "name": "dementia_daly_per_100k", "description": "Disability-adjusted life years (DALYs) from Alzheimer's disease and other dementias, both sexes, all ages", "unit": "DALYs per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://api.ourworldindata.org/v1/indicators/969489.data.json", "caveat": "Modelled estimate (see dementia_deaths_total caveat). Crude/all-ages, not age-standardized. DALYs = years of life lost to premature death (YLL) + years lived with disability (YLD); for dementia the YLD component dominates and rests on modelled disease-severity distributions, adding another layer of estimation uncertainty beyond the mortality data alone." }, "question": "Does national health spending associate with dementia burden?", "rationale": "Health-system capacity against modelled burden. Companion to I1 with a spending rather than output measure of wealth.", "design": "Ecological cross-section, 217 countries (193 with spending data).", "triage": "Spending and GDP are near-collinear; report them together or say which one the card uses and why.", "group": "geography", "n_units": 217, "exposure_coverage": 88.9, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "I4", "level": "country", "panel": "panel_country", "exposure": { "name": "dementia_plan_exists", "description": "Country has a national dementia plan/strategy (self-reported)", "unit": "1/0", "year": "2017 (WHO Global Dementia Observatory baseline survey wave)", "source_name": "WHO Global Dementia Observatory (GDO)", "source_url": "https://ghoapi.azureedge.net/api/GDO_q2x1", "caveat": "GDO is a voluntary member-state self-report survey; only 61 of 217 countries have ever submitted a response to this question (51 with a clear Yes/No — the rest were 'Under development' and left blank here as neither 1 nor 0). Non-response does not mean no plan exists — it means the country hasn't reported into GDO. A later GDO survey wave may exist but was not found accessible via this API pull; treat this as a 2017 snapshot, not current status." }, "outcome": { "name": "dementia_daly_per_100k", "description": "Disability-adjusted life years (DALYs) from Alzheimer's disease and other dementias, both sexes, all ages", "unit": "DALYs per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://api.ourworldindata.org/v1/indicators/969489.data.json", "caveat": "Modelled estimate (see dementia_deaths_total caveat). Crude/all-ages, not age-standardized. DALYs = years of life lost to premature death (YLL) + years lived with disability (YLD); for dementia the YLD component dominates and rests on modelled disease-severity distributions, adding another layer of estimation uncertainty beyond the mortality data alone." }, "question": "Do countries with a national dementia plan have different dementia burden?", "rationale": "Policy adoption against burden. Only 51 of 217 countries carry the flag, so power is limited and the coverage caveat is the headline.", "design": "Ecological cross-section, 51 of 217 countries have the exposure.", "triage": "Strong selection: countries with plans are richer and better-measured. The comparison is rich-vs-poor as much as plan-vs-no-plan. Report the income distribution of both groups before any coefficient.", "group": "geography", "n_units": 217, "exposure_coverage": 23.5, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": "Thin coverage: dementia_plan_exists at 24%", "verdict": "partial", "is_group_first": false }, { "id": "I5", "level": "country", "panel": "panel_country", "exposure": { "name": "pct_air_pollution_exposure", "description": "Population exposed to PM2.5 levels exceeding the WHO guideline value", "unit": "% of total population", "year": "2017 for all countries (single global vintage)", "source_name": "World Bank (based on satellite-derived PM2.5 modeling, Brauer et al./Global Burden of Disease-adjacent methodology but published directly by WB, not IHME)", "source_url": "https://api.worldbank.org/v2/country/all/indicator/EN.ATM.PM25.MC.ZS?format=json&per_page=20000", "caveat": "This WB series was not updated after 2017 at the time of this pull — every country's value is from the same year, so it carries no over-time variation and should be treated as a fixed structural exposure proxy, not a current reading. Use pm25_avg_ugm3 (WHO, 2023) for a more current concentration measure." }, "outcome": { "name": "dementia_deaths_per_100k_age_std", "description": "Death rate from Alzheimer's disease and other dementias, both sexes", "unit": "deaths per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://ourworldindata.org/grapher/death-rate-from-alzheimers-other-dementias-ghe ; raw values via https://api.ourworldindata.org/v1/indicators/969491.data.json", "caveat": "IMPORTANT: despite the column name (kept for schema consistency with the task spec), this is WHO GHE's crude, all-ages death rate ('age_group_allages' in the source's own variable short-name), NOT age-standardized. It is therefore NOT safe to compare directly across countries with very different age structures without also controlling for pct_65plus/median_age in your regression — an older country will show a mechanically higher crude dementia death rate even with identical age-specific risk. True age-standardized GBD dementia mortality exists but sits behind the same IHME access wall described above." }, "question": "Is population exposure to air pollution associated with dementia mortality internationally?", "rationale": "The international counterpart to S1, with a much wider exposure range than US states provide.", "design": "Ecological cross-section, 217 countries (194 with the exposure).", "triage": "Air-pollution exposure itself tracks industrialisation and therefore income and measurement. Run I1's income correlation first as the baseline this must exceed.", "group": "geography", "n_units": 217, "exposure_coverage": 89.4, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "J1", "level": "country", "panel": "panel_country", "exposure": { "name": "gini", "description": "Gini index of income inequality", "unit": "index, 0-100", "year": "latest per country, 1992-2025", "source_name": "World Bank (mostly PovcalNet/household survey based)", "source_url": "https://api.worldbank.org/v2/country/all/indicator/SI.POV.GINI?format=json&per_page=20000", "caveat": "Survey-dependent and irregularly updated — 'latest' year varies enormously by country (some countries' latest available Gini is over a decade old), so cross-country comparability is weaker than for annually-updated series. Lowest coverage of the economic block (171/217)." }, "outcome": { "name": "dementia_deaths_per_100k_age_std", "description": "Death rate from Alzheimer's disease and other dementias, both sexes", "unit": "deaths per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://ourworldindata.org/grapher/death-rate-from-alzheimers-other-dementias-ghe ; raw values via https://api.ourworldindata.org/v1/indicators/969491.data.json", "caveat": "IMPORTANT: despite the column name (kept for schema consistency with the task spec), this is WHO GHE's crude, all-ages death rate ('age_group_allages' in the source's own variable short-name), NOT age-standardized. It is therefore NOT safe to compare directly across countries with very different age structures without also controlling for pct_65plus/median_age in your regression — an older country will show a mechanically higher crude dementia death rate even with identical age-specific risk. True age-standardized GBD dementia mortality exists but sits behind the same IHME access wall described above." }, "question": "Is national income inequality associated with age-standardised dementia mortality, independent of income level?", "rationale": "I1-I5 test national wealth, spending, policy, and pollution, but none test how income is DISTRIBUTED within a country - a distinct construct from GDP per capita.", "design": "Ecological cross-section, 217 countries (171 with the gini value).", "triage": "Gini has much lower coverage than most economic columns here (171/217) and is irregularly updated across countries (see column caveat), so treat the n as a genuine constraint. Control for gdp_per_capita_usd - inequality and income level both move with development and with recording capacity (see I1).", "group": "geography", "n_units": 217, "exposure_coverage": 78.8, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": "Thin coverage: gini at 79%", "verdict": "partial", "is_group_first": false }, { "id": "J2", "level": "country", "panel": "panel_country", "exposure": { "name": "physicians_per_1000", "description": "Physicians per 1,000 people", "unit": "per 1,000 population", "year": "latest per country, 1980-2023", "source_name": "World Bank (WHO Global Health Workforce Statistics)", "source_url": "https://api.worldbank.org/v2/country/all/indicator/SH.MED.PHYS.ZS?format=json&per_page=20000", "caveat": "Reporting years vary widely by country; some 'latest' values are quite old." }, "outcome": { "name": "dementia_deaths_per_100k_age_std", "description": "Death rate from Alzheimer's disease and other dementias, both sexes", "unit": "deaths per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://ourworldindata.org/grapher/death-rate-from-alzheimers-other-dementias-ghe ; raw values via https://api.ourworldindata.org/v1/indicators/969491.data.json", "caveat": "IMPORTANT: despite the column name (kept for schema consistency with the task spec), this is WHO GHE's crude, all-ages death rate ('age_group_allages' in the source's own variable short-name), NOT age-standardized. It is therefore NOT safe to compare directly across countries with very different age structures without also controlling for pct_65plus/median_age in your regression — an older country will show a mechanically higher crude dementia death rate even with identical age-specific risk. True age-standardized GBD dementia mortality exists but sits behind the same IHME access wall described above." }, "question": "Is national physician supply associated with recorded dementia mortality?", "rationale": "The international counterpart to the state-level diagnostic-supply questions (S5, B5), using a direct workforce measure rather than income or spending as the supply proxy.", "design": "Ecological cross-section, 217 countries (208 with the exposure).", "triage": "Physician density tracks national wealth closely. Control for gdp_per_capita_usd - the I1 finding (that income predicts recorded mortality) is the baseline this must exceed to say anything about supply specifically.", "group": "geography", "n_units": 217, "exposure_coverage": 95.9, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "J3", "level": "country", "panel": "panel_country", "exposure": { "name": "pct_urban", "description": "Urban population as % of total population", "unit": "%", "year": "latest per country, mostly 2025", "source_name": "World Bank", "source_url": "https://api.worldbank.org/v2/country/all/indicator/SP.URB.TOTL.IN.ZS?format=json&per_page=20000", "caveat": "National definitions of 'urban' vary by country and are not harmonized by WB." }, "outcome": { "name": "dementia_daly_per_100k", "description": "Disability-adjusted life years (DALYs) from Alzheimer's disease and other dementias, both sexes, all ages", "unit": "DALYs per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://api.ourworldindata.org/v1/indicators/969489.data.json", "caveat": "Modelled estimate (see dementia_deaths_total caveat). Crude/all-ages, not age-standardized. DALYs = years of life lost to premature death (YLL) + years lived with disability (YLD); for dementia the YLD component dominates and rests on modelled disease-severity distributions, adding another layer of estimation uncertainty beyond the mortality data alone." }, "question": "Is a country's urbanization level associated with dementia burden?", "rationale": "Urban and rural environments differ in air quality, social structure, healthcare access, and diagnostic reach, and this column has not been tested against any outcome in the catalogue.", "design": "Ecological cross-section, 217 countries.", "triage": "Urbanization rises with national income almost everywhere. Control for gdp_per_capita_usd before treating any association as an urban/rural effect rather than a restated development gradient.", "group": "geography", "n_units": 217, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "J4", "level": "country", "panel": "panel_country", "exposure": { "name": "literacy_rate", "description": "Literacy rate, adult total (% of people ages 15+)", "unit": "%", "year": "latest per country, 1970-2024", "source_name": "World Bank (UNESCO Institute for Statistics)", "source_url": "https://api.worldbank.org/v2/country/all/indicator/SE.ADT.LITR.ZS?format=json&per_page=20000", "caveat": "High-income countries frequently do not report (assumed ~universal, so WB leaves them blank) — treat missing as 'not reported', not 'illiterate'/zero. 170/217 coverage." }, "outcome": { "name": "dementia_deaths_per_100k_age_std", "description": "Death rate from Alzheimer's disease and other dementias, both sexes", "unit": "deaths per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://ourworldindata.org/grapher/death-rate-from-alzheimers-other-dementias-ghe ; raw values via https://api.ourworldindata.org/v1/indicators/969491.data.json", "caveat": "IMPORTANT: despite the column name (kept for schema consistency with the task spec), this is WHO GHE's crude, all-ages death rate ('age_group_allages' in the source's own variable short-name), NOT age-standardized. It is therefore NOT safe to compare directly across countries with very different age structures without also controlling for pct_65plus/median_age in your regression — an older country will show a mechanically higher crude dementia death rate even with identical age-specific risk. True age-standardized GBD dementia mortality exists but sits behind the same IHME access wall described above." }, "question": "Is national adult literacy associated with recorded dementia mortality?", "rationale": "The international, wider-range counterpart to the state-level education question (S4), which found education positively associated with recorded mortality - an artifact signature this can test for at a much larger contrast in education levels.", "design": "Ecological cross-section, 217 countries (170 with the literacy value).", "triage": "High-income countries often do not report a literacy rate at all because it is assumed near-universal (see column caveat: missing is not zero), which will itself bias the sample toward lower-income countries. Control for gdp_per_capita_usd and report the coverage gap plainly - this is the same designed artifact test as S4, expected to run in the same direction.", "group": "geography", "n_units": 217, "exposure_coverage": 78.3, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": "Thin coverage: literacy_rate at 78%", "verdict": "partial", "is_group_first": false }, { "id": "J5", "level": "country", "panel": "panel_country", "exposure": { "name": "measles_immunization_pct", "description": "Immunization, measles (% of children ages 12-23 months)", "unit": "%", "year": "latest per country, mostly 2023-2024", "source_name": "World Bank / WHO-UNICEF Estimates of National Immunization Coverage (WUENIC)", "source_url": "https://api.worldbank.org/v2/country/all/indicator/SH.IMM.MEAS?format=json&per_page=20000", "caveat": "Used here only as the task-specified generic health-system-strength proxy; not causally related to dementia." }, "outcome": { "name": "dementia_deaths_per_100k_age_std", "description": "Death rate from Alzheimer's disease and other dementias, both sexes", "unit": "deaths per 100,000 population", "year": "latest per country, 2000-2021 (most countries: 2021)", "source_name": "WHO Global Health Estimates (GHE) 2021 update, via Our World in Data indicator export", "source_url": "https://ourworldindata.org/grapher/death-rate-from-alzheimers-other-dementias-ghe ; raw values via https://api.ourworldindata.org/v1/indicators/969491.data.json", "caveat": "IMPORTANT: despite the column name (kept for schema consistency with the task spec), this is WHO GHE's crude, all-ages death rate ('age_group_allages' in the source's own variable short-name), NOT age-standardized. It is therefore NOT safe to compare directly across countries with very different age structures without also controlling for pct_65plus/median_age in your regression — an older country will show a mechanically higher crude dementia death rate even with identical age-specific risk. True age-standardized GBD dementia mortality exists but sits behind the same IHME access wall described above." }, "question": "Is childhood measles immunization coverage associated with recorded dementia mortality?", "rationale": "This column's own documentation describes it as a generic health-system-strength proxy with no plausible direct link to dementia. It is included specifically as a second, cleaner test of I1's finding that recorded dementia mortality tracks measurement/health-system capacity rather than disease burden - a strong correlation here would be hard to explain any other way.", "design": "Ecological cross-section, 217 countries (193 with the exposure).", "triage": "This is a designed artifact test, not a risk-factor question. Control for gdp_per_capita_usd; if the association survives that adjustment, it strengthens the case that this outcome column measures health-system reach as much as disease.", "group": "geography", "n_units": 217, "exposure_coverage": 88.9, "exposure_exists": true, "outcome_coverage": 88.5, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "A1", "level": "state", "panel": "panel_cognitive", "exposure": { "name": "scd_reported__overall", "description": "scd_reported", "unit": "percent of older adults", "year": 2022, "source_name": "CDC Behavioral Risk Factor Surveillance System (BRFSS), Alzheimer's Disease and Healthy Aging Data", "source_url": "https://data.cdc.gov/d/hfr9-rurv", "caveat": "See _known_limits. Stratum: Overall. Self-reported and telephone-survey based, so it reflects who was reachable and willing to answer as much as underlying prevalence." }, "outcome": { "name": "pct_depression", "description": "Percent of adults ever told they have a depressive disorder", "unit": "percent", "year": 2024, "source_name": "America's Health Rankings, Depression (CDC BRFSS)", "source_url": "https://www.americashealthrankings.org/explore/measures/Depression_a", "caveat": "Tennessee value is 2023 (27.3%) because the 2024 BRFSS row for TN was marked unavailable nationally; all other states are 2024." }, "question": "Do states where more older adults report subjective cognitive decline also report more depression?", "rationale": "The first study in the catalogue whose outcome is a self-reported cognitive measure from a dedicated Alzheimer's/healthy-aging survey rather than a modelled prevalence estimate.", "design": "Ecological cross-section, 51 states and DC. BRFSS 2022 vintage.", "triage": "Both are self-reported telephone-survey measures from the SAME survey instrument, so shared method and shared non-response can inflate the coefficient. A strong result here may be measuring who answers the phone, not who is depressed.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "A2", "level": "state", "panel": "panel_cognitive", "exposure": { "name": "care_for_dementia__overall", "description": "care_for_dementia", "unit": "percent of older adults", "year": 2022, "source_name": "CDC Behavioral Risk Factor Surveillance System (BRFSS), Alzheimer's Disease and Healthy Aging Data", "source_url": "https://data.cdc.gov/d/hfr9-rurv", "caveat": "See _known_limits. Stratum: Overall. Self-reported and telephone-survey based, so it reflects who was reachable and willing to answer as much as underlying prevalence." }, "outcome": { "name": "nursing_home_beds_per_1000", "description": "Nursing home beds per 1,000 population age 65+", "unit": "rate per 1000 (65+ population)", "year": 2026, "source_name": "Becker's Hospital Review, States ranked by nursing home beds per capita (May 2026), using Census population + KFF CNF bed data", "source_url": "https://www.beckershospitalreview.com/post-acute/states-ranked-by-nursing-home-beds-per-capita/", "caveat": "IMPORTANT: denominator is population 65+, not total population -- NOT directly comparable to hospital_beds_per_1000, which is per 1,000 TOTAL population." }, "question": "Do states where more people care for someone with dementia have fewer nursing-home beds?", "rationale": "A substitution question: informal family care and institutional capacity are alternative ways of meeting the same need, and this tests whether the data shows that trade-off at state level.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Direction is genuinely ambiguous - states may have fewer beds because families cope, or more family care may be recorded because beds are scarce. The design cannot separate those; say so on the card.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "A3", "level": "state", "panel": "panel_cognitive", "exposure": { "name": "scd_reported__65_years_or_older", "description": "scd_reported", "unit": "percent of older adults", "year": 2022, "source_name": "CDC Behavioral Risk Factor Surveillance System (BRFSS), Alzheimer's Disease and Healthy Aging Data", "source_url": "https://data.cdc.gov/d/hfr9-rurv", "caveat": "See _known_limits. Stratum: 65 years or older. Self-reported and telephone-survey based, so it reflects who was reachable and willing to answer as much as underlying prevalence." }, "outcome": { "name": "alz_prevalence_65plus_pct", "description": "Estimated percentage of the population age 65+ living with Alzheimer's dementia", "unit": "percent", "year": 2020, "source_name": "Alzheimer's Association 2025 Alzheimer's Disease Facts and Figures, Table 5 (data from Dhana et al., state/county prevalence model)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Modeled estimate based on 2020 age/sex/race population distributions, not a direct case count or registry; published in the 2025 F&F report." }, "question": "Does self-reported cognitive decline agree with the modelled Alzheimer's prevalence estimate?", "rationale": "A validation question, and the most useful one in this group. One number is what people SAY about their memory; the other is a modelled prevalence built from age structure. If they disagree, that disagreement is a finding about which measure a reader should trust for what purpose.", "design": "Ecological cross-section, 51 states and DC.", "triage": "A LOW correlation is the informative outcome here, not a high one. Do not present a strong correlation as validation - the measures are constructed differently on purpose and are not supposed to be interchangeable.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "A4", "level": "state", "panel": "panel_cognitive", "exposure": { "name": "care_20h_plus_week__overall", "description": "care_20h_plus_week", "unit": "percent of older adults", "year": 2022, "source_name": "CDC Behavioral Risk Factor Surveillance System (BRFSS), Alzheimer's Disease and Healthy Aging Data", "source_url": "https://data.cdc.gov/d/hfr9-rurv", "caveat": "See _known_limits. Stratum: Overall. Self-reported and telephone-survey based, so it reflects who was reachable and willing to answer as much as underlying prevalence." }, "outcome": { "name": "unpaid_caregiver_hours_millions", "description": "Hours of unpaid care provided by family/other caregivers", "unit": "count (millions of hours)", "year": 2024, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 10", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "US total 19,161 million hours (~19.2 billion)." }, "question": "Do states with more intensive caregiving also report more total unpaid caregiving hours?", "rationale": "A consistency check between two independent caregiving series - one a survey intensity measure, the other an aggregate hours estimate. Convergence would support both.", "design": "Ecological cross-section, 51 states and DC.", "triage": "The aggregate hours column scales with state population, so it must be normalised per capita before the comparison or the correlation restates population size.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "A5", "level": "state", "panel": "panel_cognitive", "exposure": { "name": "scd_reported__overall", "description": "scd_reported", "unit": "percent of older adults", "year": 2022, "source_name": "CDC Behavioral Risk Factor Surveillance System (BRFSS), Alzheimer's Disease and Healthy Aging Data", "source_url": "https://data.cdc.gov/d/hfr9-rurv", "caveat": "See _known_limits. Stratum: Overall. Self-reported and telephone-survey based, so it reflects who was reachable and willing to answer as much as underlying prevalence." }, "outcome": { "name": "pct_hearing_loss", "description": "Percent of adults with any hearing loss", "unit": "percent", "year": 2016, "source_name": "CDC/NCHS, Any Hearing Loss by State, National Health Interview Survey 2014-2016 (Blackwell & Norris)", "source_url": "https://www.cdc.gov/nchs/data/health_policy/hearing_loss_table_SEs.pdf", "caveat": "Oldest data-year in the risk-factor block (2014-2016 pooled); no newer full 51-state BRFSS hearing-loss table was locatable in this session." }, "question": "Is self-reported cognitive decline associated with hearing loss across states?", "rationale": "Hearing loss is one of the best-supported modifiable dementia risk factors, and both of these are self-reported measures, so this pairs a supported exposure against a cognitive outcome from the same survey family.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Hearing loss and cognitive decline are both strongly age-related, so age adjustment is essential. The 65+ strata exist for both and should be used rather than the overall figures.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "A6", "level": "state", "panel": "panel_cognitive", "exposure": { "name": "care_provided__overall", "description": "care_provided", "unit": "percent of older adults", "year": 2022, "source_name": "CDC Behavioral Risk Factor Surveillance System (BRFSS), Alzheimer's Disease and Healthy Aging Data", "source_url": "https://data.cdc.gov/d/hfr9-rurv", "caveat": "See _known_limits. Stratum: Overall. Self-reported and telephone-survey based, so it reflects who was reachable and willing to answer as much as underlying prevalence." }, "outcome": { "name": "medicaid_ltss_spend_per_capita", "description": "Medicaid dementia spending per capita (total state population)", "unit": "usd per capita", "year": 2025, "source_name": "Derived by this project: medicaid_dementia_spend_total_usd / pop_total", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Computed value, not published directly. Numerator is 2025-projected dementia-specific Medicaid spend (Table 22); denominator is 2024 total population (Census), so there is a 1-year vintage mismatch between numerator and denominator. Also note this is total dementia-related Medicaid spend, not specifically LTSS/long-term-services-and-supports spend, which was not separately available by state." }, "question": "Does the share of adults providing care track per-capita long-term-services spending?", "rationale": "Informal care and public spending are the two main ways dementia care is funded. This tests whether they move together across states or substitute for each other.", "design": "Ecological cross-section, 51 states and DC.", "triage": "Spending reflects policy choice as much as need, and states differ in how generously they means-test. Treat any association as descriptive of policy regimes, not of care demand.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "A7", "level": "state", "panel": "panel_cognitive", "exposure": { "name": "scd_with_consequence__65_years_or_older", "description": "scd_with_consequence", "unit": "percent of older adults", "year": 2022, "source_name": "CDC Behavioral Risk Factor Surveillance System (BRFSS), Alzheimer's Disease and Healthy Aging Data", "source_url": "https://data.cdc.gov/d/hfr9-rurv", "caveat": "See _known_limits. Stratum: 65 years or older. Self-reported and telephone-survey based, so it reflects who was reachable and willing to answer as much as underlying prevalence." }, "outcome": { "name": "alz_deaths_per_100k", "description": "Unadjusted (not age-adjusted) annual Alzheimer's death rate per 100,000 population", "unit": "rate per 100k", "year": 2022, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 6 (NCHS)", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report explicitly presents UNADJUSTED rates (not age-adjusted) so that larger/older-population states aren't penalized in the comparison; do not treat as age-standardized." }, "question": "Do states where more adults 65+ report functional consequences from subjective cognitive decline have higher Alzheimer's mortality?", "rationale": "A3 compares self-reported decline against modelled prevalence - two survey-adjacent measures. This pairs the more clinically meaningful BRFSS measure (decline WITH a reported functional consequence, at the 65+ stratum specifically) against a hard, non-survey outcome for the first time in this group.", "design": "Ecological cross-section, 51 states and DC. BRFSS 2022 vintage.", "triage": "Both self-reported survey participation and death-certificate coding of Alzheimer's as underlying cause track socioeconomic factors. Control for median_household_income before reading the association as a disease-severity signal.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "A8", "level": "state", "panel": "panel_cognitive", "exposure": { "name": "care_for_dementia__65_years_or_older", "description": "care_for_dementia", "unit": "percent of older adults", "year": 2022, "source_name": "CDC Behavioral Risk Factor Surveillance System (BRFSS), Alzheimer's Disease and Healthy Aging Data", "source_url": "https://data.cdc.gov/d/hfr9-rurv", "caveat": "See _known_limits. Stratum: 65 years or older. Self-reported and telephone-survey based, so it reflects who was reachable and willing to answer as much as underlying prevalence." }, "outcome": { "name": "geriatricians_count", "description": "Number of board-certified geriatricians practicing in the state (bonus column, not in required spec)", "unit": "count", "year": 2021, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 14, citing American Geriatrics Society", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "2021 is the most recent year available in the source report; included as a bonus workforce-supply column alongside primary_care_physicians_per_100k and neurologists_per_100k." }, "question": "Do states where more older adults report caring for someone with dementia have more geriatricians?", "rationale": "A2 and A6 pair caregiving measures against beds and spending. This tests the specialist-workforce side directly, and restricts the caregiving measure to the 65+ stratum - caregivers who are themselves older, the clinically relevant group named in this brief - rather than the all-ages figure used elsewhere.", "design": "Ecological cross-section, 51 states and DC.", "triage": "geriatricians_count is a raw headcount (see S6), so it mechanically tracks state population size rather than workforce density. Control for pop_65plus - without that, any correlation restates how many older residents a state has, not workforce supply.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false }, { "id": "A9", "level": "state", "panel": "panel_cognitive", "exposure": { "name": "care_expected__65_years_or_older", "description": "care_expected", "unit": "percent of older adults", "year": 2022, "source_name": "CDC Behavioral Risk Factor Surveillance System (BRFSS), Alzheimer's Disease and Healthy Aging Data", "source_url": "https://data.cdc.gov/d/hfr9-rurv", "caveat": "See _known_limits. Stratum: 65 years or older. Self-reported and telephone-survey based, so it reflects who was reachable and willing to answer as much as underlying prevalence." }, "outcome": { "name": "unpaid_caregiver_value_usd", "description": "Estimated economic value of unpaid caregiving", "unit": "usd", "year": 2024, "source_name": "Alzheimer's Association 2025 Facts and Figures, Table 10", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/", "caveat": "Report gives this in millions of dollars; value here is that figure x1,000,000. Valued at a blend of state minimum wage and median home-health-aide hourly cost (a conservative estimate per the report's own methodology note). US total $413,454 million (~$413.5 billion)." }, "question": "Do states where more older adults expect to become caregivers have a higher total economic value of unpaid caregiving?", "rationale": "care_expected is a forward-looking measure, distinct from current caregiving (care_provided, used in A6) or caregiving intensity (care_20h_plus_week, used in A4). Pairing it with the total economic-value column - not yet used elsewhere in this catalogue - tests whether anticipated informal-care burden among older adults themselves lines up with the scale of caregiving actually happening.", "design": "Ecological cross-section, 51 states and DC.", "triage": "unpaid_caregiver_value_usd is a state total, not a rate (see S11's identical issue with caregiver hours), so it mechanically tracks state population. Control for pop_65plus before treating any association as a behavioral link rather than a population-size effect.", "group": "geography", "n_units": 51, "exposure_coverage": 100.0, "exposure_exists": true, "outcome_coverage": 100.0, "outcome_exists": true, "blocked_by": null, "verdict": "ready", "is_group_first": false } ] }