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Principal Investigator: Paola Gilsanz
Organization: UNIVERSITY OF CALIFORNIA AT DAVIS
Fiscal Year: 2024
Award: $3,627,096
Funding agency: National Institute on Aging
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.
Terms: <21+ years old><65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><AD dementia><AD related dementia><ADRD><Acceleration><Acculturation><Address><Adult><Adult Human><Age><Aged 65 and Over><Aging><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer risk factor><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimer's and related dementias><Alzheimer's disease and related dementia><Alzheimer's disease and related disorders><Alzheimer's disease or a related dementia><Alzheimer's disease or a related disorder><Alzheimer's disease or related dementia><Alzheimer's disease related dementia><Alzheimer's disease risk><Alzheimers Dementia><Amentia><Amyloid><Amyloid Substance><Asian group><Asian individual><Asian people><Asian population><Asians><Aβ burden><Behavioral><Biological Markers><Black><Black Populations><Black group><Black individual><Black people><Black race><Blacks><Blood Vessels><Brain><Brain Nervous System><Brain Vascular Trauma><Brain imaging><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cerebrovascular Trauma><Cerebrum><Check-up><Childhood><Clinical><Clinical Protocols><Cognitive><Cognitive Discrimination><Cognitive Disturbance><Cognitive Impairment><Cognitive aging><Cognitive decline><Cognitive function abnormal><Cohort Studies><Community Health><Concurrent Studies><Consent><Cultural Assimilation><Data><Data Collection><Data Linkages><Decrease disparity><Dementia><Development><Differences between sexes><Differs between sexes><Discrimination><Disparities><Disparity><Disturbance in cognition><Education><Educational aspects><Elderly><Encephalon><Enrollment><Epidemiologic Methods><Epidemiological Methods><Epidemiological Techniques><Ethnic Group><Ethnic Origin><Ethnic People><Ethnic Population><Ethnic individual><Ethnicity><Ethnicity People><Ethnicity Population><Exposure to><Face><Family member><Female><Future><Goals><Health><Heterogeneity><History><Image><Impaired cognition><Incidence><Individual><Infrastructure><Investigation><Latino><Latino Population><Latino group><Latino individual><Latino people><Latinos><Life><Life Cycle><Life Cycle Stages><Life Experience><Life Style><Lifestyle><Long-term cohort><Longitudinal cohort><Longterm cohort><Lower disparity><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Measures><Medical><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medical Records><Methods Epidemiology><Mothers><NMR Imaging><NMR Tomography><Nerve Degeneration><Neuron Degeneration><Nuclear Magnetic Resonance Imaging><Outcome><Outcome Study><PET><PET Scan><PET imaging><PETSCAN><PETT><Participant><Pathology><Phase><Population Heterogeneity><Position><Positioning Attribute><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Prevalence><Primary Senile Degenerative Dementia><Psychometrics><Public Health><Racial Group><Rad.-PET><Record Linkage Study><Recording of previous events><Reporting><Research><Risk><Risk Reduction><Role><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Security><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Sex Differences><Sexual differences><Stress><Time><United States><Vascular Brain Injury><Visit><Woman><Zeugmatography><a-beta burden><abeta burden><above age 65><adulthood><advanced age><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age of 65 years onward><aged 65 and greater><aged 65+><aged brain><aged ≥65><ages><aging brain><alzheimer risk><amyloid burden><beta amyloid burden><bio-markers><biologic marker><biomarker><brain visualization><cardiovascular risk><cardiovascular risk factor><cerebral><checkup><checkup examination><childhood adversity><clinical phenotype><co-morbid><co-morbidity><cognitive change><cognitive dysfunction><cognitive loss><cohort><community-based health><comorbidity><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><developmental><disparities in race><disparity due to race><disparity in ethnic><disparity in health><disparity reduction><diverse populations><early onset><enroll><ethnic based disparity><ethnic disadvantage><ethnic disparity><ethnic inequality><ethnic inequity><ethnic subgroup><ethnicity disparity><ethnicity group><ethnoracial><experience><faces><facial><geriatric><health disparity><healthy aging><healthy human aging><heterogeneous population><high risk><high school><histories><human old age (65+)><imaging><inequality due to race><inequity due to race><injury to the vasculature><interest><late life><life course><life-time risk><lifetime risk><men><mid life><mid-life><middle age><middle aged><midlife><mild cognitive disorder><mild cognitive impairment><mitigate disparity><mortality><neural degeneration><neural imaging><neuro-imaging><neurodegeneration><neurodegenerative><neuroimaging><neuroimaging biomarker><neuroimaging marker><neurological degeneration><neurological imaging><neuronal degeneration><neuropathologic><neuropathological><neuropathology><old age><over 65 years><pediatric><pediatric adversity><population diversity><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><predictive biomarkers><predictive marker><predictive molecular biomarker><primary degenerative dementia><programs><prospective><psychosocial><race based disparity><race based inequality><race based inequity><race disparity><race related disparity><race related inequality><race related inequity><racial disparity><racial diversity><racial inequality><racial inequity><racial population><racial subgroup><racially diverse><racially unequal><recruit><reduce disparity><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><reduction in disparity><risk-reducing><senile dementia of the Alzheimer type><senior citizen><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><social role><vascular><vascular injury><β-amyloid burden><βamyloid burden><≥65 years>