{
"generated_from": [
"risk_factors.json",
"genetics.json",
"prevention_trials.json",
"trials.csv"
],
"figures": {
"paf": {
"id": "fig-paf",
"title": "The 14 modifiable risk factors, ranked by modelled share of cases",
"subtitle": "Weighted population-attributable fraction (PAF): the modelled share of dementia cases a factor is associated with across a whole population, colour-coded by the life stage the Commission assigns it to.",
"svg": "",
"caption": "Source: Livingston G et al., Lancet Commission on dementia prevention, intervention and care, 2024 report, Table 1 (Lancet 2024;404(10452):572-628). These are modelled estimates of an eliminated risk factor's effect on a whole population, not measurements, and not a personal-risk calculator.",
"table": {
"columns": [
"Risk factor",
"Life stage",
"Weighted PAF",
"Effect size",
"Evidence"
],
"rows": [
[
"Hearing loss",
"Midlife",
"7%",
"RR 1.37 (95% CI 1.00-1.87); a separate larger analysis gives HR 1.35 (95% CI 1.26-1.45)",
"high"
],
[
"High LDL cholesterol",
"Midlife",
"6.9%",
"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)",
"moderate"
],
[
"Social isolation",
"Later life",
"4.6%",
"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)",
"moderate"
],
[
"Less education",
"Early life",
"4.5%",
"RR 1.6 (95% CI 1.3-2.0)",
"high"
],
[
"Depression",
"Midlife",
"3%",
"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)",
"high"
],
[
"Traumatic brain injury",
"Midlife",
"2.9%",
"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)",
"high"
],
[
"Air pollution",
"Later life",
"2.6%",
"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",
"moderate"
],
[
"Physical inactivity",
"Midlife",
"2.4%",
"RR 1.2 (95% CI 1.2-1.3)",
"moderate"
],
[
"Smoking",
"Midlife",
"2.3%",
"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",
"high"
],
[
"Diabetes",
"Midlife",
"2.3%",
"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",
"high"
],
[
"Hypertension",
"Midlife",
"2.2%",
"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)",
"moderate"
],
[
"Untreated vision loss",
"Later life",
"2.2%",
"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)",
"moderate"
],
[
"Obesity",
"Midlife",
"1.4%",
"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)",
"moderate"
],
[
"Excessive alcohol consumption",
"Midlife",
"1%",
"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",
"moderate"
]
]
}
},
"gene": {
"id": "fig-gene",
"title": "Genetic and family-history risk, ranked",
"subtitle": "Odds ratios / relative risks for the strongest common genetic and familial signals, none of which are modifiable. PSEN1, PSEN2, APP and Down syndrome are not on this chart: they cause disease deterministically rather than raising odds, so an odds ratio would misrepresent them (see the causal-mutation panel above).",
"svg": "",
"caption": "Sources: APOE and family history \u2014 Farrer LA et al., JAMA 1997; Cannon-Albright LA et al., Neurology 2019. TREM2 \u2014 Bellenguez C et al., Nat Genet 2022 (largest available GWAS; smaller early studies reported higher TREM2 odds ratios that later shrank in bigger samples, a pattern called winner's-curse shrinkage).",
"table": {
"columns": [
"Variant / history",
"Effect size",
"Source"
],
"rows": [
[
"APOE \u03b54/\u03b54 (two copies)",
"14.9\u00d7",
"Farrer LA, Cupples LA, Haines JL, et al., JAMA 1997 (pooled meta-analysis, 40 research teams, 5,930 AD cases, 8,607 controls)"
],
[
"Family history, 2+ relatives",
"4\u00d7",
"Cannon-Albright LA, et al., Neurology 2019 (Utah Population Database, 270,818 individuals, 4,436 AD deaths)"
],
[
"APOE \u03b53/\u03b54 (one copy)",
"3.2\u00d7",
"Farrer LA, Cupples LA, Haines JL, et al., JAMA 1997 (pooled meta-analysis, 40 research teams, 5,930 AD cases, 8,607 controls)"
],
[
"TREM2 R47H variant",
"2.4\u00d7",
"Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)"
],
[
"Family history, 1+ relative",
"1.7\u00d7",
"Cannon-Albright LA, et al., Neurology 2019 (Utah Population Database, 270,818 individuals, 4,436 AD deaths)"
],
[
"TREM2 R62H variant",
"1.4\u00d7",
"Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)"
]
]
}
},
"life": {
"id": "fig-life",
"title": "The life course, with real trials placed at the ages they enrolled",
"subtitle": "Early life, midlife and later-life bands follow the Lancet Commission's own cut-points (45 and 65). Each line below is one trial's actual enrollment age range, not a claim about when its intervention 'should' happen.",
"svg": "",
"caption": "Trial age ranges are copied from each study's own reporting. 'Worked' / 'no effect' / 'mixed' / 'harmful' repeats that trial's own primary result, not a judgement about the whole strategy.",
"table": {
"columns": [
"Trial",
"Ages enrolled",
"Result"
],
"rows": [
[
"API ADAD Colombia (PSEN1 carriers, crenezumab)",
"30\u201360",
"null"
],
[
"CRHCP (village-doctor-led hypertension control)",
"40+",
"positive"
],
[
"SPRINT MIND (intensive blood-pressure control)",
"50+",
"mixed"
],
[
"Maintain Your Brain (online lifestyle coaching)",
"55\u201377",
"positive"
],
[
"FINGER (multidomain lifestyle)",
"60\u201377",
"positive"
],
[
"US POINTER (structured lifestyle)",
"60\u201379",
"mixed"
],
[
"ASPREE (daily low-dose aspirin)",
"70+",
"null"
],
[
"GEM (Ginkgo biloba)",
"75+",
"null"
]
]
}
},
"mech": {
"id": "fig-mech",
"title": "Registered trials by drug mechanism",
"subtitle": "Interventional Alzheimer's trials on ClinicalTrials.gov with an identifiable drug mechanism (trials of non-drug interventions, diagnostics, and unclassified drugs are not shown).",
"svg": "",
"caption": "n = 510 trials with a classified drug mechanism, out of 7816 total registered trials in our ClinicalTrials.gov catalogue. Cholinesterase inhibitors dominate by count because they have been studied since the 1990s; anti-amyloid antibodies are the newest and fastest-growing category.",
"table": {
"columns": [
"Mechanism",
"Registered trials"
],
"rows": [
[
"Symptomatic: cholinesterase inhibitors",
332
],
[
"Anti-amyloid antibody",
99
],
[
"Anti-inflammatory",
25
],
[
"Gene therapy",
15
],
[
"GLP-1 receptor agonist",
13
],
[
"Anti-amyloid aggregation (small molecule)",
11
],
[
"BACE inhibitor",
9
],
[
"Anti-tau antibody",
6
]
]
}
}
}
}