Kaplan · Proceedings of the National Academy of Sciences of the United States of America 2023 · cross-sectional observational study · n=1165

Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations.

Level 3 - non-randomized controlled study

Cross-sectional comparative observational study in humans

PubMed 36940322 · doi:10.1073/pnas.2205448120 · record verified 2026-08-26

What was done

The authors evaluated brain volume across middle and older age (ages 40 to 94) in two indigenous South American populations, the Tsimane and Moseten (n = 1,165). They analyzed cross-sectional differences in brain volume decline with age and assessed associations between brain volume, energy biomarkers (body mass index and non-HDL cholesterol), and aortic arteriosclerosis.

What was found

The relationship between brain volume and both body mass index and non-HDL cholesterol was curvilinear, showing positive associations from the lowest values up to 1.4 to 1.6 standard deviations above the mean, and negative associations thereafter. The more acculturated Moseten showed a steeper age-related decline in brain volume than the Tsimane, though both populations had shallower declines than reported industrialized cohorts. Aortic arteriosclerosis was associated with lower brain volume. Exact effect sizes, confidence intervals, and p-values were not reported in the abstract.

Why it matters

These findings suggest that moderate body mass and lipid levels may be neuroprotective in physically active, food-limited environments, challenging standard assumptions about cardiovascular risk factors and brain aging.

Limits

The study is cross-sectional rather than longitudinal, preventing causal inference about brain atrophy rates. The abstract lacks specific numerical effect estimates, variance parameters, and details on adjustment for potential confounders.