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Dementia risk is not one thing that switches on in old age. Different factors act at different points across a life, some are still changeable when they act and some are not, and medicines have been studied at very different disease stages. This page lines all three up against real ages, from real trials.
It is a summary of modelled, population-level estimates and real trials' own enrollment ages. It is not a promise about any individual. The Lancet Commission's 45% figure describes what might happen across an entire population if every one of 14 factors were eliminated everywhere — it says nothing about what will happen to one specific person who changes one habit. Most of the risk-factor evidence below is association from observational studies, not proof of cause and effect; that caveat applies throughout, even where it is not repeated on every line.
Nothing here is medical advice. Decisions about testing, medicines or major lifestyle change belong in a conversation with your own clinician.
How to read the labels: Measured counted, surveyed or written in law. Modelled estimate produced by a statistical model — an estimate, not a count. Basis not stated the source did not say which.
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.
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| Trial | Ages enrolled | Result |
|---|---|---|
| API ADAD Colombia (PSEN1 carriers, crenezumab) | 30–60 | null |
| CRHCP (village-doctor-led hypertension control) | 40+ | positive |
| SPRINT MIND (intensive blood-pressure control) | 50+ | mixed |
| Maintain Your Brain (online lifestyle coaching) | 55–77 | positive |
| FINGER (multidomain lifestyle) | 60–77 | positive |
| US POINTER (structured lifestyle) | 60–79 | mixed |
| ASPREE (daily low-dose aspirin) | 70+ | null |
| GEM (Ginkgo biloba) | 75+ | null |
Most of the individually modelled risk sits in midlife: 10 of the 14 Lancet Commission factors are assigned there, versus one in early life and three in later life. That is a genuine finding worth sitting with, not an accident of how this page is organised — but it is still a modelled, population-level pattern, not a schedule for any one person's life.
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.
Genetically-determined familial Alzheimer's (PSEN1, PSEN2 or APP mutations) is the one Alzheimer's story that truly starts in early life — deterministically, not as a raised probability. See the genetic risk section for what that does and does not mean.
Who: cognitively unimpaired PSEN1 Glu280Ala (E280A) kindred members aged 30-60 in Medellin, Colombia; 85 crenezumab carriers, 84 placebo carriers, 83 placebo non-carriers; 63% women (ages 30-60)
What was tried: crenezumab (anti-amyloid-beta antibody) subcutaneous 300 mg then 720 mg every 2 weeks, later optional 60 mg/kg IV every 4 weeks, vs placebo, for 5-8 years in cognitively unimpaired mutation carriers; mutation non-carriers received placebo as a masked kindred control
What was found: API ADAD composite annualised change -1.10 (SE 0.29) crenezumab vs -1.43 (0.29) placebo, difference 0.33 (95% CI -0.48 to 1.13); FCSRT-CI -0.03 vs -0.04, difference 0.01 (95% CI 0.00 to 0.02)
Who: carriers of dominantly inherited AD mutations, asymptomatic and mildly symptomatic (CDR 0-1), within -15 to +10 years of estimated symptom onset; 52 gantenerumab, 52 solanezumab, 40 placebo (ages adults 15 years before to 10 years after estimated symptom onset (ages not given in abstract))
What was tried: gantenerumab (subcutaneous anti-aggregated-amyloid antibody) or solanezumab (IV anti-monomeric antibody) vs placebo, 3:1 per drug arm, 4-7 years, in asymptomatic and symptomatic autosomal-dominant mutation carriers
What was found: neither drug showed a beneficial effect on cognitive measures vs controls; solanezumab group showed greater cognitive decline on some measures; gantenerumab significantly reduced amyloid plaques, CSF total tau and p-tau181 and attenuated NfL increases
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.
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.
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.
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).
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.
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.
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.
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).
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.
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.
Who: US/Puerto Rico ambulatory adults >=50 with hypertension and elevated cardiovascular risk, without diabetes or prior stroke; 102 sites (ages 50+ (mean 67.9))
What was tried: intensive antihypertensive treatment to systolic BP goal <120 mm Hg vs standard goal <140 mm Hg
What was found: probable dementia HR 0.83 (95% CI 0.67-1.04), 7.2 vs 8.6 per 1000 person-years (149 vs 176 cases) -- not significant; MCI HR 0.81 (95% CI 0.69-0.95), 14.6 vs 18.3 per 1000 PY; MCI or probable dementia HR 0.85 (95% CI 0.74-0.97), 20.2 vs 24.1 per 1000 PY
Who: adults >=40 with uncontrolled hypertension in 326 rural Chinese villages (163 intervention, 163 usual care) (ages 40+)
What was tried: non-physician community healthcare provider-led stepped-care antihypertensive titration to systolic <130 / diastolic <80 mm Hg (with physician supervision, home BP monitoring, health coaching) vs usual care; village-level cluster randomisation
What was found: all-cause dementia RR 0.85 (95% CI 0.76-0.95); net SBP reduction 22.0 mm Hg (95% CI 20.6-23.4), DBP reduction 9.3 mm Hg (95% CI 8.7-10.0); serious adverse events RR 0.94 (95% CI 0.91-0.98)
Who: dementia-free community-dwelling Australians aged 55-77 with modifiable dementia risk factors (45 and Up Study cohort); 64% female (ages 55-77)
What was tried: 3-year online, personalised multidomain coaching in 2-4 modules targeting physical activity, nutrition, cognitive activity (computerised brain training) and depression/anxiety, vs control receiving module-eligible information only
What was found: change in z score 0.28 (95% CI 0.25-0.32) intervention vs 0.10 (95% CI 0.07-0.13) control; between-group difference 0.18 (95% CI 0.13-0.23)
Who: cognitively unimpaired adults 55-80 with intermediate or elevated brain amyloid; plasma Abeta42/40 used to screen before PET; recruitment via TRC-PAD, ADNeT and J-TRC registries (ages 55-80)
What was tried: lecanemab (BAN2401) IV, dose regimens tailored to baseline amyloid: A3 (intermediate amyloid ~20-40 centiloids, phase 2, PET endpoints) and A45 (elevated amyloid >40 centiloids, phase 3, cognitive composite primary) vs placebo, 4-year treatment
Who: adults 55-80 in the US and Japan with AD pathology detected by plasma p-tau217; 63,124 screened, 2196 enrolled (CDR-Global 0 n=1202; 0.5 n=664); mean baseline amyloid 63.2 centiloids (CDR 0) and 70.7 (CDR 0.5) (ages 55-80)
What was tried: donanemab IV monthly x9 infusions vs placebo, then clinical assessments every 6 months (decentralized design, plasma p-tau217 eligibility)
AHEAD 3-45 and TRAILBLAZER-ALZ 3 above are testing amyloid-targeting antibodies (lecanemab, donanemab) in cognitively unimpaired people ages 55–80 who have amyloid on a brain scan — a biomarker-selected, presymptomatic-prevention idea. This is not the approved use of either drug and neither trial has reported results yet.
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.
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.
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.
Who: Finnish community-dwelling at-risk older adults (CAIDE Dementia Risk Score >=6, cognition at mean or slightly lower than expected for age), recruited from national surveys (ages 60-77)
What was tried: multidomain lifestyle: diet + exercise + cognitive training + vascular risk monitoring, 2 years, vs general health advice control
What was found: between-group difference in change of NTB total Z score per year 0.022 (95% CI 0.002-0.042); mean 2-year change 0.20 intervention vs 0.16 control
Who: US older adults at risk of cognitive decline: sedentary lifestyle + suboptimal diet + >=2 of family history of memory impairment, cardiometabolic risk, race/ethnicity, older age, sex; 5 US sites (ages 60-79)
What was tried: structured high-intensity multidomain lifestyle (physical + cognitive activity, MIND-style healthy diet, social engagement, cardiovascular health monitoring; team-based with coaching and accountability) vs self-guided lower-intensity version of the same domains. NOTE: no no-intervention/usual-care control arm.
What was found: annual rate of increase 0.243 SD (95% CI 0.227-0.258) structured vs 0.213 SD (95% CI 0.198-0.229) self-guided; between-group difference 0.029 SD/year (95% CI 0.008-0.050)
Who: community-dwelling adults >=70 (US minorities >=65) in US and Australia, free of CVD, disability and dementia (ages 70+ (US minorities 65+))
What was tried: low-dose aspirin 100 mg daily vs placebo
What was found: dementia triggers HR 1.03 (95% CI 0.91-1.17); probable AD HR 0.96 (95% CI 0.74-1.24); MCI HR 1.12 (95% CI 0.92-1.37); cognitive change similar
Who: community volunteers >=75 with normal cognition (n=2587) or MCI (n=482); 5 US academic centres; 2000-2008 (ages 75+)
What was tried: Ginkgo biloba extract 120 mg twice daily vs placebo
What was found: all-cause dementia HR 1.12 (95% CI 0.94-1.33), P=0.21 (3.3 vs 2.9 per 100 person-years); AD HR 1.16 (95% CI 0.97-1.39), P=0.11; MCI-to-dementia HR 1.13 (95% CI 0.85-1.50), P=0.39
Mechanism: Reversible acetylcholinesterase inhibitor; increases synaptic acetylcholine availability
Approved for: mild, moderate, and severe AD
FDA approval: 1996-11-25
Pivotal-trial result: Symptomatic cognitive benefit vs placebo across pivotal trials; not disease-modifying
Mechanism: Reversible inhibitor of both acetylcholinesterase and butyrylcholinesterase
Approved for: mild to moderate AD (also approved for Parkinson's disease dementia)
FDA approval: 2000-04-21
Pivotal-trial result: Symptomatic cognitive benefit vs placebo across pivotal trials; not disease-modifying
Mechanism: Reversible acetylcholinesterase inhibitor and nicotinic receptor modulator
Approved for: mild to moderate AD
FDA approval: 2001-02-28
Pivotal-trial result: Symptomatic cognitive benefit vs placebo across pivotal trials; not disease-modifying
Mechanism: Low-to-moderate affinity NMDA receptor antagonist; reduces excitotoxicity from excess glutamate signaling
Approved for: moderate to severe AD
FDA approval: 2003-10-16
Pivotal-trial result: Symptomatic cognitive/functional benefit vs placebo across pivotal trials; not disease-modifying
Mechanism: Humanized monoclonal antibody that selectively binds soluble amyloid-beta protofibrils, promoting their clearance
Approved for: early AD (MCI or mild dementia)
FDA approval: 2023-01-06
Pivotal-trial result: -0.45 point difference vs placebo, a 27% slowing of clinical decline (p<0.0001)
Mechanism: Humanized IgG1 monoclonal antibody targeting pyroglutamate Aβ(p3-42), a form aggregated in amyloid plaques; clears existing plaque
Approved for: early symptomatic AD (MCI or mild dementia)
FDA approval: 2024-07-02
Pivotal-trial result: 35% slowing of decline vs placebo in low/medium tau population; 22% slowing in combined (overall) population
None of these drugs prevent Alzheimer's in someone who does not yet have it. Cholinesterase inhibitors and memantine treat symptoms without changing the underlying disease course; lecanemab and donanemab are approved specifically for early symptomatic disease (mild cognitive impairment or mild dementia) with confirmed amyloid pathology, and slow — not stop — further decline. See Treatments for full indications, side effects and costs.
Interventional Alzheimer's trials on ClinicalTrials.gov with an identifiable drug mechanism (trials of non-drug interventions, diagnostics, and unclassified drugs are not shown).
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| Mechanism | Registered trials |
|---|---|
| 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 |
The life stage a trial or drug is placed in here is the age range that trial actually enrolled, or the disease stage a drug is actually indicated for -- not a claim about when someone 'should' start treatment. Amyloid-targeting antibodies are approved for early symptomatic disease (mild cognitive impairment or mild dementia with confirmed amyloid pathology), not for healthy people trying to prevent dementia; trials of that idea (AHEAD 3-45, TRAILBLAZER-ALZ 3) are still running and have not reported results.
Every figure on this page is read straight out of a file in our data folder; nothing is typed in by hand. You can download the raw data and check any row yourself. This is a summary of published research, not medical advice.