Dementia and MCI incidence were measured over a median 4.7-year follow-up in 730 Indigenous Tsimane and Moseten adults aged ≥60 (mean age 67.3; 52% male) in Amazonian Bolivia, using culture-adapted clinical assessments; risk factors including APOE ε4, vascular markers, plasma biomarkers (Aβ, p-tau, NfL), and lifestyle variables were also evaluated.
22 incident dementia cases were identified (7.40/1000 person-years; 95% CI 4.87–11.24); dementia prevalence remained <2% across all phases. APOE ε4 (HR 4.93, 95% CI 1.98–12.32) and thoracic aortic calcium >500 (HR 3.29, 95% CI 1.12–9.70) predicted incident dementia; NfL was the only plasma biomarker significant after FDR correction (OR 2.81, 95% CI 1.69–4.68). Dementia cases had 10× higher 2-year mortality than cognitively normal participants, and 100% of baseline dementia cases died by the end of Phase 3.
- Only 22 incident cases, yielding wide confidence intervals and limiting statistical power for risk factor analyses. - Plasma biomarkers were available for only a subset (11 dementia cases), making ATN profiling preliminary. - Midlife risk factor measurements were unavailable; cross-sectional risk factor data precede but do not span the full exposure window.
Dementia prevalence is strikingly low in these traditional subsistence populations, partly because survival after diagnosis is very short—clinicians working with acculturating Indigenous communities should monitor vascular risk factors and APOE ε4 status as key modifiable and genetic predictors. The near-absence of an Alzheimer's-typical amyloid/tau biomarker profile suggests vascular pathology may dominate in this context.
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