Little is known about the incidence, prevalence, and predictors of Alzheimer's disease (AD) in populations living traditional pre-industrial lifestyles similar to those experienced over human pre-history. This information is critical to determine whether AD is a byproduct of modern environments. Compared to age-matched industrialized populations, Tsimane exhibit: a) delayed atherosclerosis progression over their lifetime; b) low prevalence of diabetes and hypertension; and c) a near absence of atrial fibrillation, stroke and myocardial infarctions. At the same time Tsimane experience high rates of infection and inflammation throughout life. The two major goals of this proposal are to: 1) measure rates of cerebral atrophy and cognitive decline in association with atherosclerotic and inflammatory burden, APOE genotype and schooling, and 2) generate estimates of the prevalence and incidence of all-cause dementia and AD. Our central hypothesis is that compared to Westerners, the low rate of atherosclerosis among Tsimane will be paralleled by a slower rate of cerebral atrophy, and reduced age-related cognitive impairment. We will test the alternative hypothesis that infection and inflammation are associated with accelerated rates of cerebral atrophy and cognitive impairment. To test these predictions we propose the following specific aims, utilizing a panel study design, state-of-the-art bioimaging technology, and a representative sample of 1,310 Tsimane adults aged 40+, which comprises ~85% of the population in that age range:
Aim 1 is to conduct longitudinal assessment of cognitive impairment and dementia with measurement of physical activity between assessments;
Aim 2 is to conduct anatomic neuroimaging of the brain related to cognitive impairment, AD and other dementias;
and Aim 3 is to investigate the epidemiology of brain atrophy, cognitive impairment, AD and other dementias. This research is time-sensitive, as Tsimane are modernizing at an accelerating rate. It may be our last chance to study the natural history of AD, cerebral atrophy and cognitive impairment with a large sample in a population living a subsistence lifestyle, similar to pre- historic populations, with low rates of CVD and high rates of infectious disease. The multi- disciplinary approach will leverage 14 years of Tsimane research, including data on atherosclerosis in four arterial beds, heart disease, infection and inflammation, physical activity level, and cognitive performance. If rates of cerebral atrophy and cognitive impairment are lower among aging Tsimane, despite their high systemic inflammation and limited schooling, those findings will have important implications for our understanding of AD in the US.

Public Health Relevance

This research will provide detailed information on the impacts of cardiovascular functioning, schooling, genotype, and infectious disease on cognitive performance in a pre-industrial Native American population experiencing similar demographic conditions as those in mid-19th century Europe. Investigation of cognitive functioning in a large representative sample of forager-horticulturalist adults can reveal novel insights into the relative contributions of and interactions between environmental and genetic factors in determining rates of cognitive decline. The results, combined with measures of brain atrophy and its predictors in the US, will shed light on factors underlying cognitive resilience and the role of schooling in expanding cognitive reserve across diverse populations.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Multi-Year Funded Research Project Grant (RF1)
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Special Emphasis Panel (ZRG1-PSE-P (59)R)
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Anderson, Dallas
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University of New Mexico
Social Sciences
Schools of Arts and Sciences
United States
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Trumble, Benjamin C; Stieglitz, Jonathan; Blackwell, Aaron D et al. (2017) Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. FASEB J 31:1508-1515
Gurven, Michael; Stieglitz, Jonathan; Trumble, Benjamin et al. (2017) The Tsimane Health and Life History Project: Integrating anthropology and biomedicine. Evol Anthropol 26:54-73
Blackwell, Aaron D; Urlacher, Samuel S; Beheim, Bret et al. (2017) Growth references for Tsimane forager-horticulturalists of the Bolivian Amazon. Am J Phys Anthropol 162:441-461
Gurven, Michael; Fuerstenberg, Eric; Trumble, Benjamin et al. (2017) Cognitive performance across the life course of Bolivian forager-farmers with limited schooling. Dev Psychol 53:160-176
Kaplan, Hillard; Thompson, Randall C; Trumble, Benjamin C et al. (2017) Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. Lancet 389:1730-1739
Kaplan, Hillard; Trumble, Benjamin C; Stieglitz, Jonathan et al. (2017) Diet, atherosclerosis, and helmintic infection in Tsimane - Authors' reply. Lancet 390:2035