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Every row of the evidence table
One row per finding: what was tested, which way the result went, and how the study was built. The answer by area, and where the studies disagree, are on the main page.
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Showing 58 of 382 rows. One row per study per exposure: a study that tested two different things appears twice, once for each.
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| Exposure | Question | Direction | Outcome measured | Design | People | Effect size, as the source reported it | Source |
|---|---|---|---|---|---|---|---|
| Population burden (prevalence, incidence, lifetime risk) All modifiable factors together | Prevention |
No direction reported
whyA burden-of-disease decomposition: age-standardised rates rose slightly and population growth was the largest driver of the rise in cases. It compares no exposure, so no direction is recorded. |
Global prevalence, incidence, mortality and DALYs of young-onset dementia, 1990-2021 | modelling study | not stated | Global age standardized prevalence and incidence of dementia among people under 65 years increased from 93.39 and 16.24 per 100,000 persons in 1990 to 96.09 and 17.16 per 100,000 persons in 2021; mortality increased from 0.89 per 100,000 population to 0.91 per 100,000 population; and age standardized DALYs increased from 45.60 per 100,000 persons to 46.78 per 100,000 persons |
Translational Psychiatry
2025 ✓ Peer-reviewed PMID 39966345 |
| Population burden (prevalence, incidence, lifetime risk) All modifiable factors together | Prevention |
No direction reported
whyA lifetime-risk estimate (42% after age 55, higher in women, Black adults and APOE4 carriers) and a projection of new cases. It compares no exposure, so no direction is recorded. |
Lifetime risk of dementia from age 55, and projected annual US incident cases to 2060 | cohort study | 15,043 | The lifetime risk of dementia after age 55 years was 42% (95% confidence interval: 41-43). Rates were substantially higher in women, Black adults and APOE ε4 carriers, with lifetime risks ranging from approximately 45% to 60% in these populations. The number of US adults who will develop dementia each year was projected to increase from approximately 514,000 in 2020 to approximately 1 million in 2060 |
Nature Medicine
2025 ✓ Peer-reviewed PMID 39806070 |
| Population burden (prevalence, incidence, lifetime risk) All modifiable factors together | Prevention |
No direction reported
whyA pooled incidence and prevalence estimate with no exposure compared, so no direction is recorded. |
Pooled incidence and prevalence of frontotemporal dementia | meta-analysis | not stated | Pooled crude incidence for FTD was 2.28 (95% CI, 1.55-3.36) per 100 000 person-years and prevalence, 9.17 (95% CI, 3.59-23.42) per 100 000 people |
JAMA Neurology
2025 ✓ Peer-reviewed PMID 40920400 |
| Population burden (prevalence, incidence, lifetime risk) All modifiable factors together | Prevention |
No direction reported
whyA prevalence estimate and forecast: cases are projected to rise from 57.4 million to 152.8 million while age-standardised prevalence stays flat, with the rise attributed to population growth and ageing. It compares no exposure, so there is no direction to record. |
Number of people with dementia worldwide, 2019 and forecast to 2050 | modelling study | not stated | We estimated that the number of people with dementia would increase from 57·4 (95% uncertainty interval 50·4-65·1) million cases globally in 2019 to 152·8 (130·8-175·9) million cases in 2050. Despite large increases in the projected number of people living with dementia, age-standardised both-sex prevalence remained stable between 2019 and 2050 (global percentage change of 0·1% [-7·5 to 10·8]) |
The Lancet Public Health
2022 ✓ Peer-reviewed PMID 34998485 |
| Population burden (prevalence, incidence, lifetime risk) All modifiable factors together | Prevention |
No direction reported
whyA pooled prevalence estimate with no exposure compared, so there is no direction to record. |
Global prevalence of young-onset dementia (ages 30-64) | meta-analysis | 2,760,379 | Age-standardized prevalence estimates increased from 1.1 per 100 000 population in the group aged 30 to 34 years to 77.4 per 100 000 population in the group aged 60 to 64 years. This gives an overall global age-standardized prevalence of 119.0 per 100 000 population in the age range of 30 to 64 years, corresponding to 3.9 million people aged 30 to 64 years living with YOD in the world |
JAMA Neurology
2021 ✓ Peer-reviewed PMID 34279544 |
| Sex and gender differences (research agenda) All modifiable factors together | Prevention |
No direction reported
whyA position paper from an expert network. It sets out 12 priority research areas on sex and gender in Alzheimer's disease and reports no effect estimate. |
None measured (research agenda) | None | not stated | not established — position paper; the abstract reports no effect estimate. |
Alzheimer's & Dementia
2018 ✓ Peer-reviewed PMID 29907423 |
| Amyloid PET Centiloid positivity threshold Care, carers and services | Treatment |
No direction reported
whyA threshold-derivation meta-analysis: it converges on 18 Centiloids (data-driven) and 27 Centiloids (visual reads) and flags 11-26 as a range to read with caution. It compares no exposure, so no direction exists to record. |
Centiloid cutoff for amyloid PET positivity (data-driven and by visual-read correspondence) | meta-analysis | 49,227 | The data-driven GMM approach identified a bimodal distribution in 51 studies (n = 48 786), resulting in a single cutoff for positivity of 18 Centiloids (95% CI,16-19; I2 = 97%). The double-cutoff approach revealed high confidence for interpreting scans as negative when Centiloid values were lower than 11 (95% CI, 9-13; I2 = 95%) and interpreting scans as positive if Centiloid values were higher than 26 (95% CI, 24-28; I2 = 95%) ... Centiloids were highly predictive of visual positivity (Cohen κ, 0.86; 95% CI, 0.83-0.89; I2 = 96%) with a cutoff of 27 Centiloids (95% CI, 24-30; I2 = 80%) |
JAMA
2026 ✓ Peer-reviewed PMID 42441390 |
| Amyloid and tau PET (appropriate use criteria) Care, carers and services | Treatment |
No direction reported
whyAppropriate use criteria rated by consensus: for amyloid PET seven of 17 scenarios were rated appropriate, two uncertain and eight rarely appropriate; for tau PET five, six and six. No effect estimate is reported. |
None measured (appropriate use criteria) | systematic review | not stated | not established — consensus criteria; the abstract reports scenario ratings, not an effect estimate. |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 39776249 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
No direction reported
whyAn editorial reviewing the FDA clearance of the Lumipulse plasma ratio test. It relays performance figures from the FDA summary and other studies and reports no data of its own. |
None measured (editorial on the FDA clearance) | None | not stated | FDA approval was based on clinical evidence showing strong agreement between plasma test results and confirmation by PET or CSF testing, with over 90% consistency in those with positive findings. In contrast, these reference methods confirmed 97.3% of those with negative plasma results to be amyloid negative |
Annals of Medicine and Surgery
2026 ⚠ Editorial — not peer-reviewed research PMID 41675863 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
No direction reported
whyA clinical practice guideline. It sets performance thresholds for blood tests (at least 90% sensitivity and 75% specificity for triage; at least 90% for both to substitute for amyloid PET or CSF) and reports no effect estimate of its own. |
None measured (clinical practice guideline) | systematic review | not stated | not established — guideline; recommendations rather than an effect estimate. |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 40729527 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
No direction reported
whyA price-threshold model: it estimates the test price at which diagnostic cost per true-positive case equals standard care ($290-$1,950 depending on use), and compares no actual price against it, so there is no direction to record. |
Value-based price of a blood test for AD pathology as a triage or confirmatory test in primary and specialty care, and projected reduction in PET/CSF use | modelling study | not stated | If used in primary care, the value-based price would be $290 for a triage and $1150 for a confirmatory test, respectively, as use of PET or CSF testing would decline by 47 % and 86 %, respectively. If used in specialty care, i.e., after confirmation of early-stage cognitive impairment, the overall number of blood tests would decline. Consequently, the value-based price would increase to $450 for a triage test and $1950 for a confirmatory test |
Journal of Prevention of Alzheimer's Disease
2025 ✓ Peer-reviewed PMID 40494736 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
No direction reported
whyA workgroup recommendations document. It sets target sensitivity and specificity for blood biomarker tests (≥90% / ≥85% for triage in primary care; ~90% / ~90% as a confirmatory test) and reports no data of its own. |
None measured (performance recommendations) | None | not stated | not established — recommendations document; the abstract states target performance thresholds, not an effect estimate. |
Nature Reviews Neurology
2024 ✓ Peer-reviewed PMID 38866966 |
| Caregiving itself (exposure to the carer) Care, carers and services | Treatment |
No direction reported
whyA pooled prevalence among carers (50.8% lonely, 37.1% socially isolated) with no non-carer comparison, so no direction for the effect of caregiving can be recorded. |
Prevalence of loneliness and social isolation among informal carers | meta-analysis | 11,134 | The pooled prevalence of loneliness among informal carers of individuals with dementia was 50.8% (95% CI: 41.8%-59.8%), while the pooled prevalence of social isolation was 37.1% (95% CI: 26.7%-47.6%) |
International Journal of Geriatric Psychiatry
2024 ✓ Peer-reviewed PMID 38752797 |
| Cost of dementia care Care, carers and services | Treatment |
No direction reported
whyA cost estimate ($818 billion, 80% of it borne by families through unpaid care, earnings losses, out-of-pocket costs and quality-of-life losses) with no exposure compared, so no direction is recorded. |
Total cost of dementia in the United States in 2026 | modelling study | not stated | In 2026, 5.7 million (95% confidence interval [CI] [5.6, 6.0]) US adults aged 51 and older are living with dementia, supported by 5.2 million (95% CI [4.9, 5.5]) care partners. Total costs are $818 billion (B, 95% CI [759, 866]), driven by quality-of-life losses for persons with dementia ($320B, 95% CI [269, 363]) and care partners ($15B 95% CI [6, 25]). Unpaid care ($237B, 95% CI [220, 253]), earnings losses ($23B), and out-of-pocket costs combined with quality-of-life losses account for 80% of costs and are borne by families |
Alzheimer's & Dementia
2026 ✓ Peer-reviewed PMID 42340126 |
| Cost of dementia care Care, carers and services | Treatment |
No direction reported
whyA descriptive spending analysis with no exposure compared, so there is no direction to record: Part D spending rose with dual-eligibility duration, Part B drug spending varied widely by state, and ACO enrollment made only a modest difference. |
Medicare Part D and Part B drug spending and out-of-pocket costs among fee-for-service beneficiaries with dementia, by dual eligibility, state and ACO enrollment | cross-sectional study | 1,372,696 | Medicare Part D drug spending was substantial, increasing with dual-eligibility duration: $8732-$9107 among beneficiaries with full-year dual eligibility and exceeding $11 500 among those with 5+ chronic conditions ... Medicare Part B drug spending was highest among Medicare-only beneficiaries and varied widely by state, ranging from $433 to $1827 among Medicare-only beneficiaries and from $179 to $1446 among dually eligible beneficiaries |
Innovation in Aging
2026 ✓ Peer-reviewed PMID 42787606 |
| Cost of dementia care Care, carers and services | Treatment |
No direction reported
whyA cost projection: total burden is estimated at $344 billion in 2020 rising to over $3 trillion in 2060, with African American and Latino families projected to bear a disproportionate share. It compares spending shares between groups but tests no exposure, so no direction is recorded. |
Total US economic burden of dementia by race and ethnicity, 2020 to 2060 | modelling study | 31,028 | The total estimated economic burden of ADRD was close to $344 billion in 2020 and was projected to increase to over $3 trillion in 2060. African American and Latino adults bore one-third ($113 billion) of it in 2020, with projections rising to $1.7 trillion by 2060, surpassing the economic burden for White adults, which was projected to grow from $231 billion to $1.4 trillion |
JAMA Network Open
2025 ✓ Peer-reviewed PMID 40471578 |
| Cost of dementia care Care, carers and services | Treatment |
No direction reported
whyA cost estimate with no exposure compared, so there is no direction to record. Higher unpaid-care costs went with lower medical spending on nursing facility care. |
Annual cost of care attributable to dementia per case in 2019 and the unpaid-care share of total cost by US state | modelling study | not stated | The annual cost of care attributable to dementia in 2019 was $53,502 (95% uncertainty interval [UI] 46,135-60,594) per case. The contribution of unpaid care to total costs varied by state, ranging from 70.2% (95% UI 64.3-75.4) in the District of Columbia to 89.9% (95% UI 87.8-91.5) in Arizona |
Journal of Alzheimer's Disease
2025 ✓ Peer-reviewed PMID 40111940 |
| Cost of dementia care Care, carers and services | Treatment |
No direction reported
whyA cost projection with no exposure compared, so there is no direction to record. Dementia's share of replacement cost is projected to rise from 44% to 53%. |
Replacement cost of unpaid family care and opportunity cost of forgone earnings for older Americans with and without dementia, now and projected to 2060 | modelling study | not stated | Current annual replacement cost of unpaid family care is between $96 and $182 billion, 44% of which is accounted for by dementia caregiving. By 2060, it will increase to $277-571 billion, and 53% will be for dementia caregiving. The opportunity costs of forgone earnings and productivity loss, however, will grow faster, increasing from current levels of $107 billion and $26 billion to $380 billion and $102 billion, respectively, in 2060 |
Innovation in Aging
2025 ✓ Peer-reviewed PMID 40662057 |
| Cost of dementia care Care, carers and services | Treatment |
No direction reported
whyA cost estimate with no exposure compared, so there is no direction to record. |
Annual indirect cost of Alzheimer's disease per person by severity, and total US indirect cost | modelling study | not stated | $36 934 for mild cognitive impairment owing to AD, $65 565 for mild AD, $103 717 for moderate AD, and $145 250 for severe AD (2024 United States Dollars [USD]). Considering the current distribution of prevalent patients across severity stages, the total annual indirect cost was estimated at $832 billion, which includes $599 billion in unpaid caregiving costs and $233 billion in productivity losses |
Value in Health
2025 ✓ Peer-reviewed PMID 39571734 |
| Cost of dementia care Care, carers and services | Treatment |
No direction reported
whyA cost estimate and projection with no exposure compared, so there is no direction to record. |
Per-patient cost of care in 2016 and aggregate US cost projected 2020-2060 | modelling study | not stated | In 2016, the estimated per patient cost of formal care was $28,078 (95% confidence interval [CI]: $25,893-$30,433), and informal care cost valued in terms of replacement cost and forgone wages was $36,667 ($34,025-$39,473) and $15,792 ($12,980-$18,713), respectively. Aggregate formal care cost and formal plus informal care cost using replacement cost and forgone wage methods were $196 billion (95% uncertainty range [UR]: $179-$213 billion), $450 billion ($424-$478 billion), and $305 billion ($278-$333 billion), respectively, in 2020. These were projected to increase to $1.4 trillion ($837 billion-$2.2 trillion), $3.3 trillion ($1.9-$5.1 trillion), and $2.2 trillion ($1.3-$3.5 trillion), respectively, in 2060 |
npj Aging
2024 ✓ Peer-reviewed PMID 38331952 |
| Cost of dementia care Care, carers and services | Treatment |
No direction reported
whyA cost estimation across 204 countries with no exposure compared, so there is no direction to record. |
Global direct health care spending and informal care cost attributable to dementia, 2019, with projection to 2050 | modelling study | not stated | in 2019, the direct health care spending attributable to ADRD across 204 countries reached $260.6 billion (95% uncertainty interval [UI] 131.6-420.4) and the cost of informal ADRD care was $354.1 billion (95% UI 190.0-544.1). On average, informal care represents 57% (95% UI 38-75%) of the total cost of care. We estimated that direct health care spending attributable to ADRD will reach $1.6 trillion (95% UI 0.6-3.3) in 2050, or 9.4% (95% UI 3.9-19.6%) of projected health spending worldwide |
Journal of Alzheimer's Disease
2024 ✓ Peer-reviewed PMID 39150827 |
| Cost-effectiveness of anti-amyloid antibody Care, carers and services | Treatment |
No direction reported
whyA threshold analysis estimating what each country should be willing to pay (from $4-$18 a year in low-income countries to $254-$9,434 for lecanemab and $387-$13,964 for donanemab in high-income countries). It sets no price against an actual list price, so there is no direction to record. |
Incremental QALYs versus usual care and value-based annual prices for lecanemab and donanemab across 174 countries | modelling study | not stated | Compared to usual care, lecanemab and donanemab respectively increased average QALYs by 0.38 and 0.51. By country income status, VBPs for lecanemab and donanemab respectively ranged between $254 to $9434 and $387 to $13,964 (high income), $90 to $1025 and $137 to $1507 (upper middle income), $11 to $623 and $21 to $956 (lower middle income) and $4 to $18 and $9 to $32 (low income) |
Alzheimer's & Dementia
2026 ✓ Peer-reviewed PMID 42125995 |
| Cost-effectiveness of anti-amyloid antibody Care, carers and services | Treatment |
No direction reported
whyA cost-effectiveness model reporting ICERs of JPY 8.5 million and 7.9 million per QALY without stating a threshold or a verdict; the authors argue that narrow value assessments understate social value. No direction is recorded. |
Incremental QALYs (patient plus caregiver) and incremental cost-effectiveness ratio of lecanemab added to standard care in Japan | modelling study | not stated | The incremental QALYs were 1.31 QALYs for MCI due to AD and 0.85 QALYs for mild AD-D, and the incremental cost-effectiveness ratios (ICERs) were JPY 8.5 million /QALY and JPY 7.9 million /QALY ($1 = JPY 150), respectively |
Journal of Alzheimer's Disease
2026 ✓ Peer-reviewed PMID 42108615 |
| Diagnostic criteria / biological definition of Alzheimer's Care, carers and services | Treatment |
No direction reported
whyA criteria document. It defines Alzheimer's disease biologically and sets out staging, and reports no effect estimate. |
None measured (diagnostic criteria document) | None | not stated | not established — criteria document; it states definitions and reports no effect estimate. |
Alzheimer's & Dementia
2024 ✓ Peer-reviewed PMID 38934362 |
| Diagnostic criteria / biological definition of Alzheimer's Care, carers and services | Treatment |
No direction reported
whyAn editorial. It argues that biomarker positivity alone should not define Alzheimer's disease in people without symptoms, and reports no data of its own. |
None measured (editorial) | None | not stated | not established — editorial read in full at jpreventionalzheimer.com; pubmed carries no abstract for it and it reports no effect estimate. |
The Journal of Prevention of Alzheimer's Disease
2024 ⚠ Editorial — not peer-reviewed research PMID 39044499 |
| Diagnostic criteria / biological definition of Alzheimer's Care, carers and services | Treatment |
No direction reported
whyA research framework defining Alzheimer's disease by biomarkers (the AT(N) system) for research use. It states its own intended limits and reports no effect estimate. |
None measured (research framework) | None | not stated | not established — framework document; the abstract reports no effect estimate. |
Alzheimer's & Dementia
2018 ✓ Peer-reviewed PMID 29653606 |
| Diagnostic evaluation and disclosure guideline Care, carers and services | Treatment |
No direction reported
whyConsensus guidance for primary care on disclosing and communicating a dementia diagnosis, developed with patients, care partners and clinicians. It reports no effect estimate. |
None measured (consensus guidance on disclosing a dementia diagnosis) | None | not stated | not established — guidance document; the abstract reports no effect estimate. |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 41085169 |
| Diagnostic evaluation and disclosure guideline Care, carers and services | Treatment |
No direction reported
whyA clinical practice guideline. It sets out a structured, patient-centred process for evaluating, diagnosing and disclosing suspected Alzheimer's disease or related dementias in any practice setting, and reports no effect estimate. |
None measured (clinical practice guideline for primary care) | systematic review | not stated | not established — guideline; the abstract reports no effect estimate. |
Alzheimer's & Dementia
2024 ✓ Peer-reviewed PMID 39713942 |
| Health-system and payment model Care, carers and services | Treatment |
No direction reported
whyA single-programme implementation report with no comparison group. It counts enrolment and service use and estimates no effect. |
Enrolment, respite use and disenrolment in the first year of one GUIDE programme | cohort study | 158 | Over 35% of eligible beneficiaries have utilized respite services. Approximately 9% have disenrolled, the majority (64%) expired/hospice |
Innovation in Aging (GSA 2025 conference abstract)
2025 ⚠ Conference abstract — not peer-reviewed DOI 10.1093/geroni/igaf122.3561 |
| Health-system and payment model Care, carers and services | Treatment |
No direction reported
whyImplementation guidance drawn from six earlier comprehensive dementia care programmes. It reports no effect estimate of its own. |
None measured (implementation guidance) | None | not stated | not established — guidance article; the abstract reports no data. the library's "up to 20% of emergency department visits ... avoidable" is a cited statistic not in… |
Journal of the American Geriatrics Society
2025 ✓ Peer-reviewed PMID 41170936 |
| MRI amygdalar atrophy scale (marker of LATE) Care, carers and services | Treatment |
No direction reported
whyA classification-validation study without a neuropathological reference standard, so accuracy cannot be judged. The groups behaved as expected: patients labelled LATE had mild amnestic impairment, limbic atrophy and stable MMSE over 30 months, while AD and AD/LATE groups declined. |
Clinical, imaging and 30-month cognitive profiles of memory-clinic patients classified as LATE, AD, AD/LATE or neither by the amygdalar atrophy scale plus AD biomarkers | cohort study | 469 | the LATE group maintained cognitive stability as the No-AD/No-LATE group (β = -0.010, 95% CI -0.096 to 0.075, p = 0.813), whereas both AD (β = -0.136, 95% CI -0.184 to -0.088, p < 0.001) and AD/LATE (β = -0.139, 95% CI -0.196 to -0.082, p < 0.001) groups showed faster decline over time |
Neurology
2026 ✓ Peer-reviewed PMID 41428981 |
| Palliative / advance care planning Care, carers and services | Treatment |
No direction reported
whyA Delphi consensus among 60 international expert panellists, reaching agreement on 15 major and 42 minor referral criteria. No patient outcome is measured and no effect is estimated. |
Consensus referral criteria for specialist palliative care (no patient outcome) | cross-sectional study | 60 | not established — delphi survey; the abstract reports consensus counts (15 major, 42 minor criteria), not an effect estimate. |
JAMA Network Open
2025 ✓ Peer-reviewed PMID 40366652 |
| Prognosis after dementia diagnosis (survival, nursing home admission) Care, carers and services | Treatment |
No direction reported
whyA prognosis meta-analysis: it pools time to death and to nursing home admission and compares no exposure. Women's shorter survival was attributable to later age at diagnosis. |
Median survival and time to nursing home admission after diagnosis | meta-analysis | 5,553,960 | Median survival from diagnosis appeared to be strongly dependent on age, ranging from 8.9 years at mean age 60 for women to 2.2 years at mean age 85 for men ... Median time to nursing home admission was 3.3 years (interquartile range 1.9 to 4.0). 13% of people were admitted in the first year after diagnosis, increasing to 57% at five years |
BMJ
2025 ✓ Peer-reviewed PMID 39778977 |
| APOE genotype Genes (not modifiable) | Prevention |
No direction reported
whyA descriptive proteomic mapping: APOE-linked protein changes were present before amyloid pathology and stable across age and disease stage, with ε2 tied to cellular-maintenance and anti-inflammatory pathways and ε4 to cell-cycle, oligodendrocyte-precursor and downstream vascular, immune and proteostatic proteins. It estimates no effect on a clinical outcome. |
Plasma and CSF proteomic signatures of APOE ε4 and ε2 across five cohorts | cross-sectional study | not stated | not established — pubmed abstract reports no numeric effect size. |
Nature Aging
2026 ✓ Peer-reviewed PMID 42141098 |
| Polygenic risk / GWAS loci Genes (not modifiable) | Prevention |
No direction reported
whyA transcriptome-wide association study prioritising nine genes (including BIN1, PTK2B and DMPK) with broadly consistent effects across populations; it reports no effect estimate for any exposure, so no direction is recorded. |
Genes whose blood expression is genetically associated with Alzheimer's disease across three populations | cross-sectional study | 751 | not established — pubmed abstract reports gene counts and a correlation (r2 ≈ 0.34 between two bin1 variants), no effect estimate. |
American Journal of Human Genetics
2026 ✓ Peer-reviewed PMID 42066773 |
| Polygenic risk / GWAS loci Genes (not modifiable) | Prevention |
No direction reported
whyLocus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. Nine signals (HP1BP3, SLC50A1, PTPRC, NPAS3, DDHD1, CHST9, SMYD2, PRAMEF1, GFRA1) appeared only in APOE-stratified analyses; DDHD1 was protective in ε4 carriers. |
New genome-wide risk loci for AD found when stratifying by APOE ε4 and ε2 carrier status | case-control study | not stated | not established — the abstract names nine new loci and prints no effect estimate. |
Nature genetics
2026 ✓ Peer-reviewed PMID 42736378 |
| Polygenic risk / GWAS loci Genes (not modifiable) | Prevention |
No direction reported
whyLocus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. The study reports 14 new loci for clinically diagnosed AD and two from AD-by-proxy. |
Genome-wide significant loci for clinically diagnosed AD and AD-by-proxy | meta-analysis | 432,374 | not established — pubmed abstract lists the loci by name and reports no effect estimate. |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 39998322 |
| Polygenic risk / GWAS loci Genes (not modifiable) | Prevention |
No direction reported
whyLocus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. The study reports eight new loci (six ancestry-specific, two trans-ancestry) and nominates eight genes in microglial activation, glutamate production and signalling. |
Genome-wide significant loci for early-onset Alzheimer's disease (onset before 70) | case-control study | 25,236 | not established — pubmed abstract reports locus counts and pathways, no effect estimate. |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 40556318 |
| Polygenic risk / GWAS loci Genes (not modifiable) | Prevention |
No direction reported
whyLocus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. Beyond APOE, the study reports TREM2 R47H and variants near RAB3B, SPOCK3/ANXA10 and SMAP2, and a gene-based association with GIPR. |
Genome-wide and exome-wide loci for Alzheimer's disease in Ashkenazi Jews | case-control study | not stated | not established — pubmed abstract reports p-values for the loci and no effect estimate. |
Alzheimer's & Dementia
2023 ✓ Peer-reviewed PMID 37260021 |
| Polygenic risk / GWAS loci Genes (not modifiable) | Prevention |
No direction reported
whyLocus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. Two signals at 17p13.2 and 18q21.33 are reported; the authors state that African ancestry at 17p13.2 went with lower AD risk and that overall African ancestry did not differ between cases and controls, without an effect estimate. |
Admixture-mapping loci for Alzheimer's disease in African Americans | case-control study | 10,271 | not established — pubmed abstract reports p-values for the two loci and no effect estimate. |
Alzheimer's & Dementia
2023 ✓ Peer-reviewed PMID 36539198 |
| Rare protective or risk variant (APOE3 Christchurch, APOE R145C, RELN, FN1) Genes (not modifiable) | Prevention |
No direction reported
whyA single case report: one man with the PSEN1 E280A mutation stayed cognitively intact until 67 despite very heavy amyloid, and carried a gain-of-function RELN variant. With one case and no comparison group beyond the earlier Christchurch case, no direction can be recorded. |
Cognitive status and amyloid/tau burden in one PSEN1 E280A carrier heterozygous for RELN-COLBOS | None | not stated | not established — case report; the abstract reports no effect estimate. |
Nature Medicine
2023 ✓ Peer-reviewed PMID 37188781 |
| Rare protective or risk variant (APOE3 Christchurch, APOE R145C, RELN, FN1) Genes (not modifiable) | Prevention |
No direction reported
whyAmong 37 heterozygous carriers (ages 56.6-82.1) none had developed AD or MCI by the March 2022 data freeze and apolipoprotein B was lower than in non-carriers, but the authors say continued follow-up is necessary and no homozygotes were found, so protection could not be tested. No incidence comparison is reported, so no direction is recorded. |
Alzheimer's disease or MCI diagnoses and blood lipid biomarkers in heterozygous APOE Christchurch carriers | cohort study | 455,306 | not established — research letter with no pubmed abstract; the full text at pmc10685495 reports carrier counts and p-values (apob p = 0.004; p = 0.036… |
Molecular Neurodegeneration
2023 ✓ Peer-reviewed PMID 38017580 |
| Brain insulin resistance ('type 3 diabetes') Heart and metabolic health | Prevention |
No direction reported
whyA narrative review arguing that Alzheimer's disease is a brain-specific form of diabetes; it states that type 2 diabetes alone "fall[s] far short of mimicking AD" and reports no effect estimate. |
Alzheimer-type neurodegeneration (mechanistic argument) | None | not stated | not established — review; the abstract reports no effect estimate. |
Journal of Diabetes Science and Technology
2008 ✓ Peer-reviewed PMID 19885299 |
| Amyloid hypothesis (target rationale) Medicines | Treatment |
No direction reported
whyA retraction notice. It withdraws the 2006 Nature paper on Aβ*56 over figures showing "signs of excessive manipulation, including splicing, duplication and the use of an eraser tool", and reports no effect estimate. |
None measured (retraction notice) | None | not stated | not established — retraction notice read at nature.com (doi 10.1038/s41586-024-07691-8) via a reader proxy; pubmed carries no abstract for it. it retracts nature doi… |
Nature
2024 ⚠ Retraction notice — not a study PMID 38914864 |
| Amyloid hypothesis (target rationale) Medicines | Treatment |
No direction reported
whyAn investigative news feature reporting signs of image fabrication in papers on the Aβ*56 amyloid oligomer. It is not a study of an outcome and reports no effect estimate. |
None measured (investigative news feature) | None | not stated | not established — news feature; no effect estimate exists. the pubmed record carries a one-sentence abstract. |
Science
2022 ⚠ News feature — not a peer-reviewed study PMID 35862524 |
| Amyloid hypothesis (target rationale) Medicines | Treatment |
No direction reported
whyA perspective review of arguments for and against the amyloid hypothesis, concluding that amyloid-beta is likely necessary but not sufficient and acts early as a trigger of tau-mediated neurodegeneration. It reports no effect estimate. |
None measured (perspective review) | None | not stated | not established — review; the abstract reports no effect estimate. |
Nature Neuroscience
2015 ✓ Peer-reviewed PMID 26007213 |
| Anti-amyloid antibody Medicines | Treatment |
No direction reported
whyMechanistic multi-omic profiling of blood from three ARIA-positive patients and three matched controls on lecanemab. It describes a clonally expanded cytotoxic CD8+ T-cell signature and estimates no clinical effect. |
Peripheral CD8+ T-cell signature in lecanemab-associated ARIA | case-control study | 6 | not established — pubmed abstract reports no numeric effect size. |
Nature Communications
2026 ✓ Peer-reviewed PMID 41617706 |
| Anti-amyloid antibody Medicines | Treatment |
No direction reported
whyA single-clinic safety series with no comparison group. It reports how often ARIA and infusion reactions happened in practice, which is useful, but it cannot estimate an effect of the drug in either direction. |
ARIA and infusion reactions in routine care | cohort study | 234 | ARIA 22%; symptomatic ARIA 5.7% overall, 27% in mild dementia vs 1.8% in MCI/very mild dementia |
JAMA Neurology
2025 ✓ Peer-reviewed PMID 40354064 |
| Anti-amyloid antibody Medicines | Treatment |
No direction reported
whyA mechanistic tissue study describing which microglial states accompany amyloid removal (TREM2 and APOE upregulation correlating with antibody response and clearance; complement signalling contributing). It estimates no effect of immunisation on a clinical outcome. |
Microglial transcriptional states associated with amyloid clearance in post-mortem brain after active (AN1792) or passive (lecanemab) immunisation | None | not stated | not established — pubmed abstract reports no numeric effect size. |
Nature Medicine
2025 ✓ Peer-reviewed PMID 40050704 |
| Anti-amyloid antibody Medicines | Treatment |
No direction reported
whyCorporate announcement discontinuing a product and terminating its confirmatory trial. It reports no clinical outcome, so no direction exists to record. |
None reported | company announcement | not stated | not established — the announcement reports a business decision and states the move was not related to safety or efficacy, so there is no effect estimate to quote. |
Biogen Inc. press release
2024 ⚠ Press release — not a study no DOI or PMID exists |
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