R01AG052132

Lifecourse Health, Cerebral Pathology, and Ethnic Disparities in Dementia (KHANDLE Study) - The KHANDLE (Kaiser Healthy Aging and Diverse Life Experiences [2R01AG052132-06] Study initiated in 2017) is a lifecourse cohort study of disparities in cognitive aging 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 encompass 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.

Davis University Of California

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Davis, California 95618 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 400% from $3,603,025 to $18,022,067.