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

Hillard Kaplan, Paul L. Hooper, Margaret Gatz, Wendy J. Mack, E. Meng Law, Helena C. Chui, M. Linda Sutherland, James D. Sutherland, Christopher J. Rowan, L. Samuel Wann, Adel H. Allam, Randall C. Thompson, David E. Michalik, Guido Lombardi, Michael I. Miyamoto, Daniel Eid Rodriguez, Juan Copajira Adrian, Raul Quispe Gutierrez, Bret A. Beheim, Daniel K. CummingsEdmond Seabright, Sarah Alami, Angela R. Garcia, Kenneth Buetow, Gregory S. Thomas, Caleb E. Finch, Jonathan Stieglitz, Benjamin C. Trumble, Michael D. Gurven, Andrei Irimia

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three hypotheses derived from an evolutionary model of brain health, which we call the embarrassment of riches (EOR). The model hypothesizes that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized societies in middle and older ages. We find that the relationship of BV with both non-HDL cholesterol and body mass index is curvilinear, positive from the lowest values to 1.4 to 1.6 SDs above the mean, and negative from that value to the highest values. The more acculturated Moseten exhibit a steeper decrease in BV with age than Tsimane, but still shallower than US and European populations. Lastly, aortic arteriosclerosis is associated with lower BV. Complemented by findings from the United States and Europe, our results are consistent with the EOR model, with implications for interventions to improve brain health.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Mar 28 2023


  • Tsimane
  • brain volume
  • evolutionary medicine
  • mismatch

ASJC Scopus subject areas

  • General


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