# Brain atrophy, cognitive impairment and Alzheimer's in a low CVD-risk population

> **NIH NIH RF1** · CHAPMAN UNIVERSITY · 2020 · $382,250

## Abstract

PROJECT SUMMARY/ABSTRACT
 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.

## Key facts

- **NIH application ID:** 10096721
- **Project number:** 3RF1AG054442-02S4
- **Recipient organization:** CHAPMAN UNIVERSITY
- **Principal Investigator:** CALEB E FINCH
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,250
- **Award type:** 3
- **Project period:** 2017-04-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10096721

## Citation

> US National Institutes of Health, RePORTER application 10096721, Brain atrophy, cognitive impairment and Alzheimer's in a low CVD-risk population (3RF1AG054442-02S4). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10096721. Licensed CC0.

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