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

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $257,006

## Abstract

PROJECT SUMMARY/ABSTRACT
 The parent grant leverages the rich, longitudinal data from the Atherosclerosis Risk in Communities (ARIC)
Study and Baltimore Longitudinal Study of Aging (BLSA) and uses a data-driven approach to characterize the
cognitive heterogeneity of subtle cognitive difficulties in older adults who do not yet show cognitive impairment
consistent with mild cognitive impairment (MCI) or dementia. We are then examining the mid- and late-life
vascular, physical activity, and Alzheimer’s disease and related dementia (ADRD) biomarker predictors of subtle
cognitive decline phenotypes (e.g., low-executive, low-memory) as well as rates of decline on ADRD outcomes.
The current proposal for a research supplement to promote diversity in health-related research would provide
funding for Fareshte Erani to complete a postdoctoral fellowship in my lab. Through this supplement, she is
proposing to extend the parent RF1 to conduct a novel examination of mid- and late-life depressive symptoms
on cognitive and biological outcomes in older adults. Her long-term career goal is to be an ADRD researcher
with an independent research program focused on the intersection of neuropsychiatric factors, neural networks,
and cognitive decline in order to guide individualized intervention efforts. Support from the diversity supplement
will leverage her existing expertise while also providing Ms. Erani with advanced training and mentorship in
ADRD research, depression and relevant cognitive outcomes and mechanisms, skills to conduct longitudinal
statistical analyses, and tools to submit an NIA K-award application.
 Depression has been associated with lower cognitive performance in older adults and increased risk for
dementia; however, there is likely considerable heterogeneity in causal mechanisms since longstanding, chronic
depression could be a causal link to subsequent cognitive impairment and/or late-life depression could be co-
occurring with an ADRD process. The proposed study will use ARIC and BLSA data to investigate the role of
depression onset and cognitive decline by examining associations of mid- and late-life onset depressive
symptoms with cognitive and biological outcomes. Specifically, we will 1) examine the extent to which mid- and
late-life depressive symptoms among cognitively unimpaired older adults predict late-life subtle cognitive decline
phenotypes and progression to MCI/dementia and 2) examine the associations of mid- and late-life depressive
symptoms with fronto-cingulate regions on neuroimaging, markers of inflammation, and ADRD plasma markers.
We will also explore neuroimaging, inflammatory, and ADRD biomarker variables that mediate the associations
of mid- and late-life depressive symptoms and subtle cognitive decline. Examining the associations between
depressive symptom onset, profiles of subtle cognitive difficulties, and the neural mechanisms that link
depressive symptoms and cognitive decline will enhance our understanding of the d...

## Key facts

- **NIH application ID:** 11080062
- **Project number:** 3RF1AG082726-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Kelsey R Thomas
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $257,006
- **Award type:** 3
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11080062

## Citation

> US National Institutes of Health, RePORTER application 11080062, Heterogeneity of subtle cognitive decline phenotypes in community-dwelling older adults (3RF1AG082726-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11080062. Licensed CC0.

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