# Lifecourse health, cerebral pathology and ethnic disparities in dementia (KHANDLE Study)

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $3,627,096

## Abstract

The KHANDLE (Kaiser Healthy Aging and Diverse Life Experiences [2R01AG052132-06] Study initiated in 2017 is
a lifecourse cohort study of disparities in cognitive ageing and Alzheimer's disease and related dementias (ADRD) in
diverse elderly individuals. KHANDLE is one of the largest lifecourse cohorts with diverse racial/ethnic composition and
prospective clinical, lifestyle, and behavioral data from 1964 -present. In Cycle 1, we enrolled 1712 individuals aged 65+
(mean age 76, range 65-103; 60% female) with representation of Blacks, Asians, Latinos, and Whites and 3 assessment
waves. We have completed 2 assessment waves, and Wave 3 will finish May 2021. All waves include comprehensive,
psychometrically sophisticated cognitive outcomes, psychosocial measures such as discrimination, stress, residential
history, a robust clinical protocol to assess prevalent and incident mild cognitive impairment (MCI) and ADRD and a 25%
subsample with amyloid PET and MRI imaging. KHANDLE participants encompasses an array of life experiences; 25%
born outside the US, 63% with mothers ≤ high school education, 28% reporting financial problems in childhood, 17%
born in Southern States, and 24.8% cognitive impairment at baseline. In this competitive renewal we extend our studies to
investigate lifecourse factors related to cognitive trajectories, brain imaging changes, and brain donation based
neuropathology with a new focus on sex differences. We will continue investigations of incident ADRD, MCI, vascular
brain injury changes and amyloid PET taking advantage of imaging in Cycle 1 and repeating in Cycle 2. We will enhance
KHANDLE with recruitment of 500 new individuals from diverse backgrounds and will investigate sex differences
leveraging retrospective data to account for selective survival. KHANDLE is uniquely positioned to address timing of
lifecourse exposures and the spectrum of cognitive and cerebropathological aging in a diverse cohort with increased
ADRD incidence and cognitive changes in the next 5 years (mean age 81 at start of Cycle 2). Our aims are: Aim 1:
Evaluate how life experiences, early- midlife health and development of comorbidities influence ADRD incidence and
cognitive trajectories over 9 years. We will use a diverse cohort to evaluate timing of cumulative exposures and will
address racial/ethnic group differences. Aim 2: Examine how lifecourse health impacts amyloid PET and structural MRI
changes and how neuroimaging biomarkers predict cognitive decline in diverse elderly. Aim 3: Investigate sex differences
in ADRD incidence and cognitive decline in a diverse cohort while investigating the role of selective survival and
competing risk of vascular mortality. Aim 4: Initiate a brain donation program for KHANDLE, characterize the spectrum
of neuropathology in a diverse cohort and evaluate predictors of interest, consent, and participation. Findings from
KHANDLE Cycle 2 will uncover mechanisms for reducing disparities in ADRD and cognitive aging.

## Key facts

- **NIH application ID:** 10867449
- **Project number:** 5R01AG052132-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Paola Gilsanz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,627,096
- **Award type:** 5
- **Project period:** 2016-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867449

## Citation

> US National Institutes of Health, RePORTER application 10867449, Lifecourse health, cerebral pathology and ethnic disparities in dementia (KHANDLE Study) (5R01AG052132-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10867449. Licensed CC0.

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