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Principal Investigator: Evan Fletcher
Organization: UNIVERSITY OF CALIFORNIA AT DAVIS
Fiscal Year: 2024
Award: $1,377,033
Funding agency: National Institute on Aging
PROJECT ABSTRACT
Alzheimer's disease and related dementias (ADRD) are known causes of cognitive and functional decline, but
some individuals are more resilient to these diseases and continue to function normally despite associated
brain changes. Cognitive reserve has been invoked to explain better cognition than expected based on the
presence and severity of disease. There is evidence modifiable lifestyle factors may build cognitive reserve;
elucidating these associations has major practical implications for public health policy and interventions to
build reserve, thus reducing the impact of ADRD and promoting healthy aging. The overarching goal of this
project is to transition from a hypothetical and often post-hoc construct of cognitive reserve to a concrete
understanding of the variables that promote resilience and the mechanisms by which they protect against
cognitive and functional decline. In this competitive renewal we will use novel imaging approaches, an
unprecedented multi-racial/ethnic sample, and prospectively collected midlife data; each of these components
constitutes a major innovation over previous studies. Aim 1 will delineate brain resources underlying cognition
and everyday function. We will employ discovery-based neuroimaging techniques to better understand the
contributions of cortical neurodegeneration, vascular brain injury, and amyloid deposition to cognitive and
functional outcomes. We will leverage four longitudinal cohorts (N = >700) with harmonized imaging,
cognitive and functional data among four major racial/ethnic groups (Latinos, non-Latino Asians, non-Latino
Blacks, and non-Latino Whites) to examine racial/ethnic group similarities and differences in brain
mechanisms underlying cognition and function. Models developed in Aim 1 will also serve to enhance the
precision by which we can operationalize cognitive reserve as residual cognition after accounting for brain
changes. We also extend our approach for cognitive reserve to operationalize functional reserve. Loss of
independence is a major concern for older adults and better understanding factors that reduce disability is
critical. Aim 2 will develop longitudinal models of cognitive and functional reserve and investigate how
dynamic reserve impacts ADRD clinical outcomes. Aim 3 will evaluate how life course risk and resilience
factors build or deplete cognitive and functional reserve and whether these relationships vary across
racial/ethnic groups. A uniquely valuable contribution of this study will be the rare ability to examine impacts
of medical, lifestyle, and psychosocial data (vascular risks, physical/cognitive activity, personality,
stress/adversity and social connection) prospectively collected in the 1960s-1990s (during midlife) in addition
to late life, thereby allowing us to answer important questions about critical periods of exposure for reserve and
its life course determinants. This project will leverage unique data, multidisciplinary expertise, and an
innovative approach for measuring brain-behavior relations underlying reserve to address important questions
about how cognitive and functional reserve contribute to late life cognitive health across diverse populations.
Terms: <AD dementia><AD pathology><AD related dementia><ADRD><Accounting><Address><Affect><Aging><Alzheimer Type Dementia><Alzheimer disease dementia><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 pathology><Alzheimer's disease related dementia><Alzheimer's pathology><Alzheimers Dementia><Amentia><Amyloid><Amyloid Substance><Amyloid deposition><Asian group><Asian individual><Asian people><Asian population><Asians><Aβ burden><Behavioral><Black Populations><Black group><Black individual><Black people><Blacks><Blood Vessels><Brain><Brain Nervous System><Brain Pathology><Brain Vascular><Brain Vascular Disorders><Brain Vascular Trauma><Buffers><Cerebrovascular Disease><Cerebrovascular Disorders><Cerebrovascular Trauma><Clinical><Cognition><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Data><Dementia><Diagnosis><Disease><Disorder><Disparities><Disparity><Disturbance in cognition><Encephalon><Ethnic Group><Ethnic Origin><Ethnic People><Ethnic Population><Ethnic individual><Ethnicity><Ethnicity People><Ethnicity Population><Goals><Grant><Health><Health Policy><Image><Impaired cognition><Individual><Intervention><Intervention Strategies><Intracranial Vascular Diseases><Intracranial Vascular Disorders><Knowledge><Label><Latino Population><Latino group><Latino individual><Latino people><Latinos><Life Cycle><Life Cycle Stages><Life Style><Lifestyle><Long-term cohort><Longitudinal cohort><Longterm cohort><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Measures><Medical><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Methods><Modeling><NMR Imaging><NMR Tomography><Nerve Degeneration><Neuron Degeneration><Nuclear Magnetic Resonance Imaging><Outcome><PET><PET Scan><PET imaging><PETSCAN><PETT><Personality><Persons><Population><Population Heterogeneity><Position><Positioning Attribute><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Primary Senile Degenerative Dementia><Public Health><Race><Races><Racial Group><Rad.-PET><Research><Research Resources><Residual><Residual state><Resources><Risk><Risk Factors><Risk Reduction><Sampling><Severity of illness><Stress><Techniques><Testing><Translating><Vascular Brain Injury><Zeugmatography><a-beta burden><abeta burden><aged brain><aging associated disease><aging brain><aging related disease><amyloid burden><beta amyloid burden><brain based><brain behavior><brain vascular disease><brain vascular dysfunction><build resilience><build resiliency><burden of disease><burden of illness><cerebral vascular><cerebral vascular disease><cerebral vascular dysfunction><cerebro-vascular><cerebrovascular><cerebrovascular dysfunction><cognitive dysfunction><cognitive function><cognitive loss><cognitive reserve><cohort><critical period><decline in function><decline in functional status><demographics><develop resilience><develop resiliency><differences due to race><differences in race><differs by race><differs in race><disability><disease burden><disease of aging><disease severity><disorder of aging><disparities in race><disparity due to race><disparity in ethnic><diverse populations><enhance resilience><enhance resiliency><ethnic based disparity><ethnic difference><ethnic disadvantage><ethnic disparity><ethnic diversity><ethnic inequality><ethnic inequity><ethnic minority group><ethnic minority individual><ethnic minority people><ethnic minority population><ethnic subgroup><ethnically diverse><ethnicity difference><ethnicity disparity><ethnicity group><functional decline><functional outcomes><functional status decline><health care policy><health goals><healthcare policy><healthy aging><healthy human aging><heterogeneous population><image-based method><imaging><imaging approach><imaging based approach><imaging method><imaging modality><improve resilience><improve resiliency><improved><increase resilience><increase resiliency><inequality due to race><inequity due to race><innovate><innovation><innovative><interventional strategy><intracranial vascular dysfunction><late life><life course><life span><life-style factor><lifespan><lifestyle factors><mid life><mid-life><middle age><middle aged><midlife><modifiable lifestyle factors><multi-racial><multidisciplinary><multiracial><neural degeneration><neural imaging><neuro-imaging><neurodegeneration><neurodegenerative><neuroimaging><neurological degeneration><neurological imaging><neuronal degeneration><novel><older adult><older adulthood><population diversity><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><prevent><preventing><primary degenerative dementia><promote resilience><promote resiliency><promoter><promotor><prospective><protective factors><psychosocial><race based differences><race based disparity><race based inequality><race based inequity><race differences><race disparity><race related differences><race related disparity><race related inequality><race related inequity><racial><racial background><racial difference><racial disparity><racial diversity><racial inequality><racial inequity><racial minority group><racial minority individual><racial minority people><racial minority population><racial origin><racial population><racial subgroup><racially different><racially diverse><racially unequal><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><resilience><resilience development><resilience factor><resiliency factor><resilient><risk-reducing><senile dementia of the Alzheimer type><social><theories><vascular><β-amyloid burden><βamyloid burden>