[
  {
    "id": "less-education",
    "factor": "Less education (early life)",
    "modifiable": true,
    "category": "other",
    "effect_size": "RR 1.6 (95% CI 1.3-2.0)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 4.5,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "Fewer years of formal education is linked to higher dementia risk, likely because education builds 'cognitive reserve' -- the brain's capacity to compensate for pathology. A Latin American meta-analysis of 31 studies found dementia prevalence of 21.4% in people with no education versus 9.9% in those with at least one year of schooling.",
    "source_name": "Lancet Commission on dementia prevention, intervention, and care, 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "Weighted PAF 4.5% (rounded 5%); prevalence of low education used in the model was 23.2%. Confounded by socioeconomic status, which the Commission partly adjusts for via its 'communality' weighting.",
    "value_type": "modelled"
  },
  {
    "id": "hearing-loss",
    "factor": "Hearing loss (midlife)",
    "modifiable": true,
    "category": "sensory",
    "effect_size": "RR 1.37 (95% CI 1.00-1.87); a separate larger analysis gives HR 1.35 (95% CI 1.26-1.45)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 7.0,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "Untreated hearing loss is one of the single largest contributors to dementia risk in the Lancet Commission's model, plausibly via reduced auditory/cognitive stimulation and social withdrawal. Each additional category of hearing-loss severity raised risk by about 16% (95% CI 1.07-1.27) in the cited literature; hearing-aid use appears to partly offset the excess risk.",
    "source_name": "Lancet Commission 2024 report (Table 1, new pooled meta-analysis of 6 cohorts, n=666,370)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "Table 1 RR 1.4 (95% CI 1.0-1.9), prevalence 59.0%, weighted PAF 7.0% (rounded 7%). Observational; reverse causation (subclinical dementia causing perceived hearing decline) not fully excluded.",
    "value_type": "modelled"
  },
  {
    "id": "hypertension",
    "factor": "Hypertension (midlife)",
    "modifiable": true,
    "category": "cardiovascular",
    "effect_size": "HR 1.42 (95% CI 1.15-1.76) for untreated hypertension vs. healthy controls; SPRINT MIND trial: probable-dementia HR 0.83 (95% CI 0.67-1.04, not significant), MCI HR 0.81 (95% CI 0.69-0.95)",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": 2.2,
    "direction": "increases-risk",
    "evidence_strength": "moderate",
    "summary": "Midlife hypertension raises dementia risk, and treating it appears protective against cognitive decline and MCI. The flagship SPRINT MIND randomized trial found intensive blood-pressure control significantly reduced MCI but its dementia-specific endpoint narrowly missed statistical significance, likely because the trial was stopped early and underpowered for that outcome.",
    "source_name": "Lancet Commission 2024 report (Table 1); Williamson et al., SPRINT MIND, JAMA 2019",
    "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6439590",
    "year": 2019,
    "notes": "Table 1 RR 1.2 (95% CI 1.1-1.4), prevalence 31.1%, weighted PAF 2.2% (rounded 2%). Blood pressure trajectories tend to drop shortly before dementia onset, complicating late-life measurement.",
    "value_type": "modelled"
  },
  {
    "id": "smoking",
    "factor": "Smoking (midlife)",
    "modifiable": true,
    "category": "lifestyle",
    "effect_size": "RR 1.30 (95% CI 1.18-1.45); UK Biobank HR 1.7 (95% CI 1.2-2.5) for smokers under 50 at baseline",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 2.3,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "Current midlife smoking substantially raises dementia risk; former smokers show little to no excess risk, suggesting quitting reduces risk at essentially any age. The 2024 Lancet Commission reclassified smoking from a late-life to a midlife risk factor based on newer evidence.",
    "source_name": "Lancet Commission 2024 report (Table 1); Zhong et al. meta-analysis, 37 studies",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "Table 1 RR 1.3 (95% CI 1.2-1.4), prevalence 22.3%, weighted PAF 2.3% (rounded 2%).",
    "value_type": "modelled"
  },
  {
    "id": "obesity",
    "factor": "Obesity (midlife)",
    "modifiable": true,
    "category": "metabolic",
    "effect_size": "RR 1.31 (95% CI 1.02-1.68), meta-analysis of 14 studies (n=77,890); central obesity (waist circumference) HR 1.10 (95% CI 1.05-1.15)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 1.4,
    "direction": "increases-risk",
    "evidence_strength": "moderate",
    "summary": "Midlife obesity raises dementia risk, but the relationship is complicated near the time of diagnosis: obesity measured within about 10 years of dementia onset can appear protective because of pre-diagnostic weight loss (reverse causation).",
    "source_name": "Lancet Commission 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "Table 1 RR 1.3 (95% CI 1.0-1.7), prevalence 13.0%, weighted PAF 1.4% (rounded 1%). Heavily confounded with diabetes, hypertension, and physical inactivity.",
    "value_type": "modelled"
  },
  {
    "id": "depression",
    "factor": "Depression (midlife/later life)",
    "modifiable": true,
    "category": "psychosocial",
    "effect_size": "RR 2.2 (95% CI 1.7-3.0) per Lancet Commission's own meta-analysis; UK Biobank HR 1.51 (95% CI 1.38-1.63)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 3.0,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "Depression at any life stage is associated with raised dementia risk, with the largest relative risk seen for early/midlife-onset depression. Effectively treated depression (UK Biobank) was associated with a lower risk, HR 0.62 (95% CI 0.53-0.73), than untreated depression.",
    "source_name": "Lancet Commission 2024 report (Table 1, new meta-analysis of 7 studies)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "2024 report reclassified depression from 'later life' to 'midlife' category. Table 1 RR 2.2 (95% CI 1.7-3.0), prevalence 7.2%, weighted PAF 3.0% (rounded 3%). Bidirectional relationship: depression can be a prodromal symptom of dementia rather than purely causal.",
    "value_type": "modelled"
  },
  {
    "id": "physical-inactivity",
    "factor": "Physical inactivity (midlife/later life)",
    "modifiable": true,
    "category": "lifestyle",
    "effect_size": "RR 1.2 (95% CI 1.2-1.3)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 2.4,
    "direction": "increases-risk",
    "evidence_strength": "moderate",
    "summary": "Physical inactivity in midlife/later life raises dementia risk; conversely, maintaining an individually optimal activity level over decades was protective (HR 0.75, 95% CI 0.58-0.97) compared with persistent inactivity in a cohort followed a median 24.5 years. See also the separate 'physical-activity' protective-factor entry.",
    "source_name": "Lancet Commission 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "2024 report reclassified physical inactivity from 'later life' to 'midlife' category. Prevalence 27.5%, weighted PAF 2.4% (rounded 2%). Reverse causation risk: preclinical dementia often reduces activity levels before diagnosis.",
    "value_type": "modelled"
  },
  {
    "id": "diabetes",
    "factor": "Diabetes (midlife)",
    "modifiable": true,
    "category": "metabolic",
    "effect_size": "RR 1.7 (95% CI 1.6-1.8); each 5-year-earlier age of type-2-diabetes onset raised risk HR 1.24 (95% CI 1.06-1.46) up to age-70 onset",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 2.3,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "Diabetes diagnosed in midlife substantially raises dementia risk via vascular damage, CNS insulin resistance, and inflammation. The Commission explicitly classifies diabetes as a midlife risk factor and notes its effect is uncertain when onset occurs late in life.",
    "source_name": "Lancet Commission 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "2024 report reclassified diabetes from 'later life' to 'midlife' category. Prevalence 9.3%, weighted PAF 2.3% (rounded 2%). Some glucose-lowering drug classes (SGLT2 inhibitors, GLP-1 agonists) show associated risk reduction in observational data, but causality is unproven.",
    "value_type": "modelled"
  },
  {
    "id": "excessive-alcohol",
    "factor": "Excessive alcohol consumption (midlife)",
    "modifiable": true,
    "category": "lifestyle",
    "effect_size": "RR 1.2 (95% CI 1.0-1.5); heavier (>21 UK units/week) vs. lighter drinking, HR 1.22 (95% CI 1.01-1.48), IPD meta-analysis n=131,415",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 1.0,
    "direction": "increases-risk",
    "evidence_strength": "moderate",
    "summary": "Heavy/excessive alcohol use in midlife raises dementia risk in a dose-dependent way; a South Korean cohort of nearly 4 million found cutting back from heavy to moderate drinking lowered risk (HR 0.92, 95% CI 0.86-0.99).",
    "source_name": "Lancet Commission 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "Prevalence 13.3%, weighted PAF 1.0% (rounded 1%). 'Non-drinker' comparison groups are often contaminated by former heavy drinkers who quit due to illness, producing a misleading J-shaped risk curve in some studies.",
    "value_type": "modelled"
  },
  {
    "id": "traumatic-brain-injury",
    "factor": "Traumatic brain injury (midlife)",
    "modifiable": true,
    "category": "other",
    "effect_size": "RR 1.7 (95% CI 1.4-1.9); meta-analysis of 21 studies (n=8,684,485), OR 1.81 (95% CI 1.53-2.14)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 2.9,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "A history of traumatic brain injury, including single mild concussions, measurably raises later dementia risk. Younger age at injury and male sex are associated with higher risk; contact-sport cohorts (e.g., professional soccer players) show elevated neurodegenerative-disease mortality.",
    "source_name": "Lancet Commission 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "Prevalence 12.1%, weighted PAF 2.9% (rounded 3%). TBI risk clusters with other risk behaviors (alcohol use, low education); the effect is attenuated but not eliminated after adjustment for confounders.",
    "value_type": "modelled"
  },
  {
    "id": "air-pollution",
    "factor": "Air pollution (later life)",
    "modifiable": true,
    "category": "environmental",
    "effect_size": "RR 1.1 (95% CI 1.1-1.1); US cohort of >18 million, black carbon (PM2.5 constituent) HR 1.12 (95% CI 1.11-1.14) per 1 ug/m3 increment",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 2.6,
    "direction": "increases-risk",
    "evidence_strength": "moderate",
    "summary": "Long-term exposure to particulate air pollution, especially black carbon, raises dementia risk. Quasi-experimental evidence from air-quality improvement policies in France found a 12.2 ug/m3 reduction in PM2.5 was associated with lower dementia risk (HR 0.85, 95% CI 0.76-0.95), supporting a reversible, plausibly causal relationship.",
    "source_name": "Lancet Commission 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "Prevalence 75.0% (i.e., most of the world's population has meaningful exposure), weighted PAF 2.6% (rounded 3%). Individual pollutant components are not fully disentangled and exposure measurement is imprecise.",
    "value_type": "modelled"
  },
  {
    "id": "social-isolation",
    "factor": "Social isolation (later life)",
    "modifiable": true,
    "category": "psychosocial",
    "effect_size": "RR 1.6 (95% CI 1.3-1.8); systematic review of 8 studies (n=15,762), RR 1.57 (95% CI 1.32-1.85)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 4.6,
    "direction": "increases-risk",
    "evidence_strength": "moderate",
    "summary": "Infrequent social contact in later life raises dementia risk, plausibly through loss of cognitive stimulation and increased stress/inflammation. A related but distinct construct, loneliness, shows RR estimates of 1.26-1.58 across separate reviews.",
    "source_name": "Lancet Commission 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "Prevalence 24.0%, weighted PAF 4.6% (rounded 5%). Studies with under 4 years of follow-up are especially prone to reverse causation (preclinical dementia causing social withdrawal, not the reverse).",
    "value_type": "modelled"
  },
  {
    "id": "vision-loss",
    "factor": "Untreated vision loss (later life)",
    "modifiable": true,
    "category": "sensory",
    "effect_size": "RR 1.5 (95% CI 1.4-1.6); meta-analysis of 14 prospective cohorts (n=6,204,827), pooled RR 1.47 (95% CI 1.36-1.60)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 2.2,
    "direction": "increases-risk",
    "evidence_strength": "moderate",
    "summary": "Vision impairment -- much of it correctable -- was newly added as a dementia risk factor in the Lancet Commission's 2024 report. Cataract surgery specifically was associated with lower subsequent dementia risk (HR 0.71, 95% CI 0.62-0.83) versus unoperated cataracts, suggesting a genuinely modifiable pathway; diabetic retinopathy also raised risk (HR 1.34, 95% CI 1.11-1.61), while glaucoma and age-related macular degeneration showed no significant association.",
    "source_name": "Lancet Commission 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "New in the 2024 report (not in the 2020 list). Prevalence 12.7%, weighted PAF 2.2% (rounded 2%). Global prevalence estimate skews toward low- and middle-income countries where untreated vision loss is more common.",
    "value_type": "modelled"
  },
  {
    "id": "high-ldl-cholesterol",
    "factor": "High LDL cholesterol (midlife)",
    "modifiable": true,
    "category": "cardiovascular",
    "effect_size": "RR 1.3 (95% CI 1.3-1.4); n=1,189,090 study of LDL >3 mmol/L, HR 1.33 (95% CI 1.26-1.41); each 1 mmol/L increase in LDL raised risk 8% (95% CI 1.03-1.14)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": 6.9,
    "direction": "increases-risk",
    "evidence_strength": "moderate",
    "summary": "Elevated LDL cholesterol in midlife (not late life) is newly recognized (2024) as a dementia risk factor. Statin use was associated with lower dementia risk (OR 0.80, 95% CI 0.75-0.86) versus untreated high cholesterol in a 36-cohort meta-analysis, though a Cochrane review of late-life statin RCTs found no benefit.",
    "source_name": "Lancet Commission 2024 report (Table 1)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "New in the 2024 report. Prevalence estimate (76.5%) is drawn from a single Norwegian cohort (HUNT study, ~37,000 participants aged 45+) because the Commission could not find a worldwide LDL prevalence estimate -- the weakest prevalence input of the 14 factors, per the Commission's own text. Weighted PAF 6.9% (rounded 7%).",
    "value_type": "modelled"
  },
  {
    "id": "apoe4-genotype",
    "factor": "APOE4 genotype (dose-dependent)",
    "modifiable": false,
    "category": "genetic",
    "effect_size": "One copy (heterozygous, e3/e4): OR 3.2 (95% CI 2.8-3.8); two copies (homozygous, e4/e4): OR 14.9 (95% CI 10.8-20.6), both vs. e3/e3 reference",
    "effect_size_type": "OR",
    "population_attributable_fraction_pct": null,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "Carrying one copy of the APOE4 allele roughly triples Alzheimer's odds; carrying two copies (homozygous) raises odds nearly 15-fold relative to the common e3/e3 genotype, a clear gene-dosage effect. The e2/e3 genotype was mildly protective (OR 0.6, 95% CI 0.5-0.8).",
    "source_name": "Farrer LA, Cupples LA, Haines JL, et al., JAMA 1997 (pooled meta-analysis, 40 research teams, 5,930 AD cases, 8,607 controls)",
    "source_url": "https://jamanetwork.com/journals/jama/fullarticle/418446",
    "year": 1997,
    "notes": "Landmark, still most-cited meta-analysis; not included in the Lancet Commission's modifiable-risk PAF model since APOE4 is non-modifiable. Effect size varies substantially by ancestry: stronger in Japanese populations (e4/e4 OR 33.1) and weaker in African American/Hispanic populations in the same meta-analysis."
  },
  {
    "id": "family-history",
    "factor": "Family history of Alzheimer's/dementia",
    "modifiable": false,
    "category": "genetic",
    "effect_size": "RR 1.73 (95% CI 1.59-1.87) for 1+ affected first-degree relative; RR 3.98 (95% CI 3.26-4.82) for 2+ affected first-degree relatives",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": null,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "Risk climbs steeply with the number of affected close relatives; risk elevation extends even to second- and third-degree relatives, indicating a broad polygenic/inherited contribution beyond APOE4 alone.",
    "source_name": "Cannon-Albright LA, et al., Neurology 2019 (Utah Population Database, 270,818 individuals, 4,436 AD deaths)",
    "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6511086",
    "year": 2019,
    "notes": "Utah-specific founder population (largely European ancestry), which may limit generalizability. The reported RR for 3+ affected first-degree relatives (2.48, 95% CI 1.07-4.89) is numerically lower than for 2+ relatives, an instability the study authors themselves note as likely due to small subgroup size."
  },
  {
    "id": "age",
    "factor": "Age",
    "modifiable": false,
    "category": "demographic",
    "effect_size": "Prevalence 5.1% (ages 65-74), 13.2% (ages 75-84), 33.4% (ages 85+)",
    "effect_size_type": "other",
    "population_attributable_fraction_pct": null,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "Age is the single strongest predictor of Alzheimer's/dementia risk; prevalence increases roughly exponentially after age 65, more than doubling with each successive decade.",
    "source_name": "Alzheimer's Association, 2025 Alzheimer's Disease Facts and Figures",
    "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/",
    "year": 2025,
    "notes": "Figures shown are modeled prevalence by age band, not a formal per-decade relative risk statistic (a single pooled RR-per-decade figure is rarely reported in this literature), but function as the standard effect-size proxy for age."
  },
  {
    "id": "sex-female",
    "factor": "Sex (being female)",
    "modifiable": false,
    "category": "demographic",
    "effect_size": "HR 1.12 (95% CI 1.02-1.23), meta-analysis of 21 cohorts (n=29,850); lifetime risk at age 65: women 24.6% vs. men 15.5% (all-cause dementia)",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": null,
    "direction": "increases-risk",
    "evidence_strength": "moderate",
    "summary": "Women show meaningfully higher lifetime dementia risk than men in Western cohort data, but the Lancet Commission attributes this substantially to women's greater life expectancy and historically lower educational attainment rather than to a clearly established sex-specific biological mechanism. The Commission's own text notes findings on sex differences are inconsistent across countries.",
    "source_name": "Lancet Commission 2024 report; Chene G, et al., Alzheimer's & Dementia 2015 (Framingham Heart Study)",
    "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4092061/",
    "year": 2015,
    "notes": "For Alzheimer's disease specifically (Framingham data), lifetime risk at 65 was 21.1% for women vs. 11.6% for men (p<0.001). Evidence is heterogeneous across countries/study designs."
  },
  {
    "id": "down-syndrome",
    "factor": "Down syndrome (trisomy 21)",
    "modifiable": false,
    "category": "genetic",
    "effect_size": "Symptomatic Alzheimer's prevalence reaches 90-100% by the seventh decade of life; lifetime risk of AD >90%",
    "effect_size_type": "other",
    "population_attributable_fraction_pct": null,
    "direction": "increases-risk",
    "evidence_strength": "high",
    "summary": "Trisomy 21 causes near-universal Alzheimer's brain pathology and very high rates of clinical dementia by late-middle-age, because the extra copy of chromosome 21 causes lifelong overexpression of the amyloid precursor protein (APP) gene. Among a cohort of 388 adults with Down syndrome, median age of Alzheimer's-dementia diagnosis was 53.7 years and median age of prodromal-AD diagnosis was 50.2 years.",
    "source_name": "Fortea J, Vilaplana E, Carmona-Iragui M, et al., The Lancet 2020",
    "source_url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30689-9/fulltext",
    "year": 2020,
    "notes": "The strongest known genetic risk factor for early-onset Alzheimer's in people who survive to middle age. Figures reflect people with Down syndrome who survive into adulthood; onset ages are typically decades earlier than late-onset Alzheimer's in the general population."
  },
  {
    "id": "mediterranean-diet",
    "factor": "Mediterranean diet adherence (protective)",
    "modifiable": true,
    "category": "lifestyle",
    "effect_size": "HR 0.89 (95% CI 0.83-0.95) for dementia (10 studies); HR 0.70 (95% CI 0.60-0.82) for Alzheimer's disease specifically (9 cohorts)",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": null,
    "direction": "decreases-risk",
    "evidence_strength": "moderate",
    "summary": "Higher adherence to a Mediterranean-style diet is associated with an 11% lower risk of dementia overall and a 30% lower risk of Alzheimer's disease specifically in pooled cohort data spanning 2000-2024.",
    "source_name": "Meta-analysis of 23 studies, 2000-2024",
    "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12181514",
    "year": 2024,
    "notes": "Purely observational; no large randomized controlled trial has confirmed causality for dementia as a primary endpoint. Residual confounding by socioeconomic status, education, and general healthy-lifestyle clustering is likely."
  },
  {
    "id": "physical-activity",
    "factor": "Physical activity (protective)",
    "modifiable": true,
    "category": "lifestyle",
    "effect_size": "HR 0.75 (95% CI 0.58-0.97) for maintaining an individually optimal activity level vs. persistent inactivity",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": null,
    "direction": "decreases-risk",
    "evidence_strength": "moderate",
    "summary": "Sustained physical activity across adulthood is associated with roughly a quarter reduction in dementia risk compared with persistent inactivity, in a cohort of 29,826 people followed a median 24.5 years with activity assessed twice a decade apart. This is the protective mirror of the 'physical-inactivity' risk-factor entry.",
    "source_name": "Lancet Commission 2024 report (cited cohort study)",
    "source_url": "https://chronicdisease.org/wp-content/uploads/2024/12/Lancet-2024.pdf",
    "year": 2024,
    "notes": "Same reverse-causation concern as inactivity: declining activity can itself be an early, pre-diagnostic dementia symptom, which may inflate the apparent protective effect of staying active."
  },
  {
    "id": "intensive-blood-pressure-control-sprint-mind-rct",
    "factor": "Intensive (systolic <120 mm Hg) vs standard (<140 mm Hg) blood-pressure treatment - SPRINT MIND trial",
    "modifiable": true,
    "category": "cardiovascular",
    "effect_size": "Probable dementia HR 0.83 (95% CI 0.67-1.04), 7.2 vs 8.6 cases per 1,000 person-years (not significant); MCI HR 0.81 (0.69-0.95), 14.6 vs 18.3 per 1,000 person-years; MCI or probable dementia HR 0.85 (0.74-0.97)",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": null,
    "direction": "no-significant-effect",
    "evidence_strength": "high",
    "summary": "The only large randomised trial of blood-pressure targets with adjudicated dementia as the primary cognitive outcome found no significant reduction in probable dementia with intensive control, although mild cognitive impairment and the combined MCI-or-dementia outcome were significantly reduced. The trial was stopped early for cardiovascular benefit, so it accrued fewer dementia cases than planned and may have been underpowered for the dementia endpoint.",
    "source_name": "SPRINT MIND Investigators for the SPRINT Research Group; Williamson JD, Pajewski NM, Auchus AP, et al. Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA 2019;321(6):553-561",
    "source_url": "https://doi.org/10.1001/jama.2018.21442",
    "year": 2019,
    "notes": "PMID 30688979; PMC6439590; NCT01206062. 9,361 adults aged >=50 with hypertension, no diabetes or prior stroke, 102 US/Puerto Rico sites; intensive n=4,678, standard n=4,683; mean age 67.9; 35.6% women; 91.5% had >=1 follow-up cognitive assessment; median intervention 3.34 years, median follow-up 5.11 years; 149 vs 176 probable-dementia cases. Recorded as a null primary result with a significant secondary (MCI) result. Complements the observational 'hypertension' record."
  },
  {
    "id": "low-dose-aspirin-aspree-rct",
    "factor": "Low-dose aspirin (100 mg daily) in healthy older adults - ASPREE trial",
    "modifiable": true,
    "category": "other",
    "effect_size": "All dementia triggers HR 1.03 (95% CI 0.91-1.17); probable AD HR 0.96 (0.74-1.24); MCI HR 1.12 (0.92-1.37); cognitive change over time similar in both arms",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": null,
    "direction": "no-significant-effect",
    "evidence_strength": "high",
    "summary": "In a large placebo-controlled trial of community-dwelling adults aged 70+ (US minorities 65+) free of cardiovascular disease and dementia, daily low-dose aspirin did not reduce incident dementia, probable Alzheimer's disease, MCI or cognitive decline over a median 4.7 years. Aspirin is therefore not a dementia-prevention strategy in healthy older people.",
    "source_name": "Ryan J, Storey E, Murray AM, et al. Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline. Neurology 2020;95(3):e320-e331",
    "source_url": "https://doi.org/10.1212/WNL.0000000000009277",
    "year": 2020,
    "notes": "PMID 32213642; PMC7455352; NCT01038583. 19,114 participants, US and Australia; 964 triggered dementia assessment; 575 adjudicated dementia cases (DSM-IV), 41% clinically probable AD. Class II evidence per the journal's classification. Deliberately recorded as a null finding."
  },
  {
    "id": "ginkgo-biloba-gem-rct",
    "factor": "Ginkgo biloba extract (120 mg twice daily) - Ginkgo Evaluation of Memory (GEM) trial",
    "modifiable": true,
    "category": "other",
    "effect_size": "All-cause dementia HR 1.12 (95% CI 0.94-1.33; P=.21); Alzheimer's disease HR 1.16 (0.97-1.39; P=.11); progression from MCI to dementia HR 1.13 (0.85-1.50; P=.39); dementia rate 3.3 vs 2.9 per 100 person-years (ginkgo vs placebo)",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": null,
    "direction": "no-significant-effect",
    "evidence_strength": "high",
    "summary": "The largest placebo-controlled trial of Ginkgo biloba, in 3,069 community volunteers aged 75+ with normal cognition or MCI followed for a median 6.1 years, found no reduction in all-cause dementia or Alzheimer's disease; point estimates were, if anything, slightly unfavourable. Ginkgo remains widely sold for memory despite this null result.",
    "source_name": "DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA 2008;300(19):2253-2262",
    "source_url": "https://doi.org/10.1001/jama.2008.683",
    "year": 2008,
    "notes": "PMID 19017911; PMC2823569; NCT00010803. 5 US academic centres, 2000-2008; ginkgo n=1,545, placebo n=1,524; 2,587 normal cognition and 482 MCI at entry; 523 incident dementia cases (277 ginkgo, 246 placebo), 92% possible/probable AD or AD with vascular disease; dropout/loss to follow-up 6.3%; similar adverse-event profiles. Null finding recorded deliberately."
  },
  {
    "id": "vitamin-e-selenium-preadvise-rct",
    "factor": "Antioxidant supplements (vitamin E, selenium, or both) - PREADViSE trial in asymptomatic older men",
    "modifiable": true,
    "category": "lifestyle",
    "effect_size": "Adjusted HR vs placebo: vitamin E 0.88 (95% CI 0.64-1.20); selenium 0.83 (0.60-1.13); combination 1.00 (0.75-1.35); dementia incidence 4.4% overall (325/7,338), not different across arms",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": null,
    "direction": "no-significant-effect",
    "evidence_strength": "moderate",
    "summary": "Neither vitamin E nor selenium, alone or together, prevented dementia in 7,540 men aged 60+ enrolled through the SELECT prostate-cancer prevention trial. The randomised phase (2002-2009) converted to an observational cohort after SELECT closed for futility, which weakens the design, but the result is consistently null.",
    "source_name": "Kryscio RJ, Abner EL, Caban-Holt A, et al. Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer's Disease by Vitamin E and Selenium Trial (PREADViSE). JAMA Neurol 2017;74(5):567-573",
    "source_url": "https://doi.org/10.1001/jamaneurol.2016.5778",
    "year": 2017,
    "notes": "PMID 28319243; PMC5506489. Mean baseline age 67.5 (SD 5.3); 52.2% college-educated; 10.0% Black; 6.7% Hispanic; 130 SELECT sites; 3,786 continued into the cohort phase (Sep 2009-May 2015); modified intent-to-treat Cox models. Men only; dementia ascertained by two-stage screen plus record review, not universal clinical evaluation. Null finding recorded deliberately."
  },
  {
    "id": "menopause-hormone-therapy",
    "factor": "Menopause hormone therapy (oestrogen-only or combined) in peri-/post-menopausal women",
    "modifiable": true,
    "category": "other",
    "effect_size": "No significant association between MHT use and incident MCI or dementia in random-effects meta-analysis of 10 studies (1 RCT, 9 observational; 1,016,055 participants); subgroups by timing, duration and type also non-significant (pooled point estimate not given in abstract)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": null,
    "direction": "no-significant-effect",
    "evidence_strength": "moderate",
    "summary": "A 2025 systematic review and meta-analysis found no evidence that menopause hormone therapy either raises or lowers dementia risk, and no effect of timing, duration or formulation. The authors conclude MHT should be prescribed for its other benefits and risks, not for dementia prevention. Certainty of evidence ranged from moderate to very low, and no study addressed premature ovarian insufficiency or testosterone.",
    "source_name": "Melville M, He L, Desai R, et al. Menopause hormone therapy and risk of mild cognitive impairment or dementia: a systematic review and meta-analysis. Lancet Healthy Longev 2025;6(12):100803",
    "source_url": "https://doi.org/10.1016/j.lanhl.2025.100803",
    "year": 2025,
    "notes": "PMID 41448220; PROSPERO CRD42025639384; primary studies searched 1 Jan 2000-20 Oct 2025; risk of bias via RoB 2 / ROBINS-E; GRADE. Funded by the Public Health Agency of Canada. The abstract reports the null result qualitatively; the numeric pooled RR was not in the loaded text, so effect_size states the finding without inventing a point estimate."
  },
  {
    "id": "statin-use-observational",
    "factor": "Statin use (observational cohorts and case-control studies)",
    "modifiable": true,
    "category": "cardiovascular",
    "effect_size": "Pooled OR 0.80 (95% CI 0.75-0.86) for dementia (36 studies) and OR 0.68 (0.56-0.81) for Alzheimer's disease (21 studies) in statin users vs non-users; men OR 0.86 (0.81-0.92) and women OR 0.86 (0.81-0.92); high-potency statins 20% vs low-potency 16% dementia risk reduction (P=0.05 for heterogeneity)",
    "effect_size_type": "OR",
    "population_attributable_fraction_pct": null,
    "direction": "decreases-risk",
    "evidence_strength": "low",
    "summary": "Pooled observational evidence associates statin use with about 20% lower odds of dementia and 32% lower odds of Alzheimer's disease, with no difference between lipophilic and hydrophilic statins. Because this is observational (healthy-user and indication bias are likely) and no adequately designed randomised trial exists, the authors frame it as absence of neurocognitive harm plus a possible favourable effect, not proof of prevention.",
    "source_name": "Olmastroni E, Molari G, De Beni N, et al. Statin use and risk of dementia or Alzheimer's disease: a systematic review and meta-analysis of observational studies. Eur J Prev Cardiol 2022;29(5):804-814",
    "source_url": "https://doi.org/10.1093/eurjpc/zwab208",
    "year": 2022,
    "notes": "PMID 34871380. Search to January 2021; restricted maximum-likelihood random-effects model. Evidence strength set to 'low' because all included studies are observational and the authors call for ad hoc RCTs. Contrast with the 'high-ldl-cholesterol' record (LDL as a risk factor) - statin benefit does not follow automatically from that association."
  },
  {
    "id": "periodontal-disease-tooth-loss",
    "factor": "Poor periodontal health (periodontitis, tooth loss, deep pockets, alveolar bone loss)",
    "modifiable": true,
    "category": "other",
    "effect_size": "Dementia HR 1.21 (95% CI 1.07-1.38; 23 longitudinal studies); cognitive decline OR 1.23 (1.05-1.44; 24 studies); tooth loss alone: dementia HR 1.13 (1.04-1.23), cognitive decline OR 1.23 (1.09-1.39); complete tooth loss dementia HR 1.23 (1.05-1.45)",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": null,
    "direction": "increases-risk",
    "evidence_strength": "low",
    "summary": "Longitudinal studies link poor periodontal health and tooth loss to roughly 20% higher dementia risk, but the review authors rate the evidence low quality, highly heterogeneous, and 'at least partly due to reverse causality' (early cognitive decline worsens oral care). Not among the Lancet Commission's 14 factors.",
    "source_name": "Asher S, Stephen R, Mantyla P, Suominen AL, Solomon A. Periodontal health, cognitive decline, and dementia: A systematic review and meta-analysis of longitudinal studies. J Am Geriatr Soc 2022;70(9):2695-2709",
    "source_url": "https://doi.org/10.1111/jgs.17978",
    "year": 2022,
    "notes": "PMID 36073186; PMC9826143. Five databases searched to April 2022; 47 studies included (24 cognitive decline, 23 dementia); random-effects pooling. Partial tooth loss OR 1.50 (1.02-2.23) for cognitive decline. Recorded with the authors' caution about reverse causality."
  },
  {
    "id": "light-to-moderate-alcohol-dose-response",
    "factor": "Light-to-moderate alcohol intake vs abstention (dose-response, longitudinal studies)",
    "modifiable": true,
    "category": "lifestyle",
    "effect_size": "Dementia: RR 0.92 (95% CI 0.88-0.96) at 1-17.5 g/day and RR 1.23 (1.09-1.35) at >17.5 g/day vs 0 g/day (J-shaped; lowest risk ~15 g/day); cognitive dysfunction: RR 0.97 (0.95-0.99) at 1-30.5 g/day and RR 1.07 (1.01-1.15) at >30.5 g/day (lowest risk ~30 g/day)",
    "effect_size_type": "RR",
    "population_attributable_fraction_pct": null,
    "direction": "decreases-risk",
    "evidence_strength": "low",
    "summary": "A 2024 dose-response meta-analysis of 17 longitudinal studies finds a J-shaped curve: light drinking (about one standard drink a day or less) is associated with slightly lower dementia risk than abstention, while heavier intake raises risk by about a quarter. The apparent protective effect of light drinking is contested because abstainer groups often include former heavy drinkers and people who stopped for health reasons (sick-quitter bias); this record should be read with the 'excessive-alcohol' record.",
    "source_name": "Zarezadeh M, Mahmoudinezhad M, Faghfouri AH, et al. Alcohol consumption in relation to cognitive dysfunction and dementia: A systematic review and dose-response meta-analysis of comparative longitudinal studies. Ageing Res Rev 2024;100:102419",
    "source_url": "https://doi.org/10.1016/j.arr.2024.102419",
    "year": 2024,
    "notes": "PMID 39038743. Search to April 2023; restricted cubic spline dose-response; 80,680 persons with 4,929 dementia cases and 13,530 persons with 1,579 cognitive-dysfunction cases. J-shape persisted in subgroups by age (<=65, >65) and study duration for dementia. Evidence strength 'low' reflects observational design and abstainer-bias concerns raised in the summary (the abstract itself does not discuss sick-quitter bias)."
  },
  {
    "id": "influenza-vaccination",
    "factor": "Influenza vaccination (observational cohorts)",
    "modifiable": true,
    "category": "other",
    "effect_size": "Overall population: HR 0.93 (95% CI 0.86-1.01), not significant; high-risk populations (CKD, COPD, vascular disease): 2-3 doses HR 0.84 (0.76-0.92), >=4 doses HR 0.43 (0.38-0.48)",
    "effect_size_type": "HR",
    "population_attributable_fraction_pct": null,
    "direction": "no-significant-effect",
    "evidence_strength": "low",
    "summary": "Across eight cohort studies with nearly 10 million people, influenza vaccination was not significantly associated with lower dementia incidence in the general population, although a dose-response association appeared in people with chronic kidney disease, COPD or vascular disease. Repeated vaccination is strongly confounded by health-seeking behaviour, so the subgroup finding should not be read as causal; contrast with the quasi-experimental zoster-vaccine record.",
    "source_name": "Yang WK, Shao SC, Liu CC, Chi CC. Influenza vaccination and risk of dementia: a systematic review and meta-analysis. Age Ageing 2025;54(7):afaf169",
    "source_url": "https://doi.org/10.1093/ageing/afaf169",
    "year": 2025,
    "notes": "PMID 40601364. Search to 6 April 2025; 8 cohort studies, 9,938,696 subjects; Newcastle-Ottawa risk of bias low in all but one study; random-effects model. Direction recorded as no-significant-effect for the overall population (the primary comparison); the authors' own conclusion emphasises the dose-response finding."
  },
  {
    "id": "education-and-occupational-complexity-cosmic",
    "factor": "High-school completion or above, and occupational complexity (COSMIC 9-cohort coordinated analysis)",
    "modifiable": true,
    "category": "other",
    "effect_size": "Pooled survival time ratio 1.26 (95% CI 1.09-1.47) for dementia-free survival with high-school completion or above vs less than high school (total effect); natural direct effect 1.18 (1.01-1.36); indirect effect via occupational complexity 1.06 (1.02-1.09); 28% of the education effect mediated by occupational complexity",
    "effect_size_type": "other",
    "population_attributable_fraction_pct": null,
    "direction": "decreases-risk",
    "evidence_strength": "moderate",
    "summary": "Across 10,195 older adults in nine cohorts from six countries, completing high school lengthened dementia-free survival by about a quarter, and adult occupational complexity independently added protection, explaining roughly a quarter of the education effect. A threshold pattern was seen: finishing high school mattered, with little extra gain from further education. Adds the adult-life occupation pathway to the 'less-education' record.",
    "source_name": "Hyun J, Hall CB, Katz MJ, et al. Education, Occupational Complexity, and Incident Dementia: A COSMIC Collaborative Cohort Study. J Alzheimers Dis 2022;85(1):179-196",
    "source_url": "https://doi.org/10.3233/JAD-210627",
    "year": 2022,
    "notes": "PMID 34776437; PMC8748312 (full text loaded). Median baseline age 74.1 (range 58-103); accelerated failure time models per cohort then meta-analysed; cumulative dementia incidence across cohorts 3%-22%. Pooled values quoted are from the mediation-analysis table (Table 5) of the full text; occupational complexity estimates in Table 4 varied by cohort (e.g., EAS Black and LEILA75+ protective) and the pooled Table 3/4 rows were in figures not captured as text."
  }
]