# Heterogeneity of subtle cognitive decline phenotypes in community-dwelling older adults

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $1,838,200

## Abstract

PROJECT SUMMARY/ABSTRACT
New submission for PA-20-185 (NOT-AG-21-020: Maximizing the Scientific Value of Secondary Analyses
of Existing Cohorts and Datasets in Order to Address Research Gaps and Foster Additional
Opportunities in Aging Research). Over the last decade, there have been increased efforts to improve early
detection of Alzheimer’s disease and related dementias (AD/ADRD), with most of these efforts focused on
pathological and biomarker changes. However, there also continues to be critical gaps in our understanding of
cognitive changes in the early stages of AD/ADRD, despite cognitive and subsequent functional changes
ultimately having the greatest direct impact on the lives of people living with AD/ADRD and their loved ones.
Specifically, little work has comprehensively investigated the cognitive heterogeneity within older adults who do
not yet meet criteria for mild cognitive impairment (MCI), but who may be showing subtle cognitive difficulties.
This subtle cognitive decline/pre-MCI phase may be a critical window of opportunity for early intervention and
planning, so refining our understanding of the earliest cognitive changes associated with AD/ADRD is crucial.
Our work using a data-driven approach to understand the heterogeneity of MCI has shown specific subtypes
beyond the traditional amnestic/non-amnestic distinction that show unique patterns of cortical thinning, AD
biomarker profiles, and rates of cognitive decline and progression to dementia. In this project, we will leverage
the rich longitudinal data from the Atherosclerosis Risk in Communities (ARIC) Study and Baltimore Longitudinal
Study of Aging (BLSA) and use a data-driven approach to characterize the cognitive heterogeneity in older adults
who do not yet show cognitive impairments consistent with MCI or dementia. The ARIC Study and BLSA include
diverse samples recruited from the community, which will allow for greater generalization of results beyond the
typical memory clinic samples. The aims of this project include: 1) Derive cognitive phenotypes among
cognitively unimpaired older adults (i.e., no MCI or dementia) using latent profile analysis of individual
neuropsychological measures, 2) Determine the mid- and late-life vascular risk factors (diabetes, hypertension),
physical activity levels, and AD biomarkers (e.g., plasma, MRI) that predict membership to the cognitive
phenotype groups (e.g., low-memory, low-executive, etc.), and 3) Examine the longitudinal outcomes associated
with the cognitive phenotypes, including rates of progression to MCI/dementia, rates of cognitive/functional
decline, and rates of brain atrophy and white matter hyperintensity volume changes. Results from this study have
the potential to improve our understanding of the types of cognitive profiles that emerge as the earliest changes
associated with AD/ADRD. Determining these unique subtle cognitive decline subtypes plus associated
biomarker and risk/resilience profiles and risk of progression...

## Key facts

- **NIH application ID:** 10713843
- **Project number:** 1RF1AG082726-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Kelsey R Thomas
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,838,200
- **Award type:** 1
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10713843

## Citation

> US National Institutes of Health, RePORTER application 10713843, Heterogeneity of subtle cognitive decline phenotypes in community-dwelling older adults (1RF1AG082726-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10713843. Licensed CC0.

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