Language

English

Publication Date

11-1-2025

Journal

Alzheimer's & Dementia

DOI

10.1002/alz.70892

PMID

41208717

PMCID

PMC12598403

PubMedCentral® Posted Date

11-10-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: Higher cognitive reserve (CR) is associated with reduced dementia risk. We hypothesized that higher CR is associated with less baseline Alzheimer's disease (AD) pathology in the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort.

Methods: A subsample of participants underwent amyloid beta and tau positron emission tomography imaging. Regression analysis was used to model the association between educational attainment (EA) as a CR proxy measure, amyloid positivity, and entorhinal cortex (ERC) and meta-temporal region of interest (meta-ROI) tau standardized uptake value ratio (SUVR).

Results: In 911 participants with complete imaging data, higher CR was significantly associated with lower ERC tau SUVR. CR was not associated with amyloid status or meta-ROI tau.

Discussion: In the U.S. POINTER cohort, higher EA predicted lower tau burden in the ERC. Meta-ROI tau levels may be too low in this cognitively unimpaired sample to reveal associations. CR may have a role in promoting biological resistance to AD pathology.

Highlights: Higher cognitive reserve is associated with a lower dementia risk and better cognitive performance after a diagnosis of Alzheimer's disease. The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk trial imaging cohort was cognitively unimpaired at baseline and a subsample received amyloid and tau positron emission tomography scans. Higher educational attainment, a proxy measure of cognitive reserve, was significantly related to tau levels in the entorhinal cortex region of interest.

Keywords

Humans, Cognitive Reserve, Positron-Emission Tomography, tau Proteins, Female, Male, Aged, Alzheimer Disease, United States, Entorhinal Cortex, Cohort Studies, Amyloid beta-Peptides, Brain, Educational Status, Alzheimer's disease, cognitive reserve, positron emission tomography imaging, tau burden, U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk

Published Open-Access

yes

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