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Principal Investigator: Deborah Allison Levine
Organization: UNIVERSITY OF MICHIGAN AT ANN ARBOR
Fiscal Year: 2024
Award: $745,455
Funding agency: National Institute on Aging
PROJECT SUMMARY/ABSTRACT
Alzheimer’s disease and Alzheimer’s disease-related dementia (AD/ADRD) incidence is high in older adults
with stroke. There is a fundamental gap in understanding how vascular risk factors (VRFs) influence risk of
post-stroke AD/ADRD. Poor understanding of the biological factors driving post-stroke AD/ADRD risk is a critical barrier to the design of interventions aimed to protect the brain health of stroke survivors. The long-term
goal is to develop, test, and disseminate VRF interventions that reduce post-stroke AD/ADRD for diverse populations. The study objective is to quantify how VRFs influence post-stroke AD/ADRD risk to inform preventive interventions tailored to stroke survivors and inform clinical care and policies. Post-stroke AD/ADRD is an
excellent model of a serious, chronic illness of aging with high prevalence and costs. High blood pressure (BP),
diabetes, and high cholesterol are ideal biological VRFs because they are common and modifiable with a wide
range of effective therapies for management. Our central hypothesis is that post-stroke VRF levels contribute
to post-stroke AD/ADRD. The rationale for the proposed research is that knowing the impact of VRF levels
and stroke (sub)type on post-stroke AD/ADRD will improve our understanding of vascular biology and translate
into new and innovative approaches for prevention of post-stroke AD/ADRD. Guided by strong preliminary
data, this hypothesis will be tested through 3 specific aims: 1) Quantify the influence of post-stroke VRF levels
on post-stroke cognitive trajectories and AD/ADRD, and explore how sex and race affect these relationships;
2) Clarify the relationships between stroke subtype and post-stroke cognitive trajectories and AD/ADRD, and
explore how VRFs, sex, and race affect these relationships; and 3) Refine and expand an existing AD/ADRD-CVD computer simulation model by adding post-stroke AD/ADRD and results from Aims 1 and 2 to quantify
the subset of stroke events, sample size, and duration of trials that are adequately powered to find clinically
important and plausible effect sizes of VRF lowering on post-stroke AD/ADRD. The results of Aims 1 and 2
will be the identification of both VRF targets for interventions to reduce post-stroke AD/ADRD risk and the sub-groups of stroke survivors most likely to benefit from VRF lowering. The results of Aim 3 will be a new simulation model applicable to stroke survivors that can be used to inform clinical research trials, clinical care, and
policies. This research is innovative because it will ultimately yield a novel simulation model that could provide
new guidance that may change clinical practice and health policy for stroke survivors. The proposed study is
significant because it will generate new knowledge and methods to understand the impact of optimal VRF
treatment intensity on post-stroke AD/ADRD risk and improve the design of VRF lowering trials in stroke survivors. Ultimately, such knowledge has the potential to inform the development of targeted interventions to improve the prevention of post-stroke AD/ADRD and to reduce AD/ADRD-related disability in older Americans.
Terms: <21+ years old><AD dementia><AD related dementia><ADRD><Address><Adult><Adult Human><Affect><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><American><Apoplexy><Approaches to prevention><Arteries><Automobile Driving><Biologic Factor><Biological><Biological Factors><Biology><Bleeding><Blood Pressure><Blood Vessels><Brain Vascular Accident><Cardiovascular Diseases><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Cholesterol><Chronic Disease><Chronic Illness><Clinical><Clinical Research><Clinical Study><Clinical Trials><Cognition><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Cohort Studies><Computer Simulation><Computer based Simulation><Concurrent Studies><D-Glucose><Data><Development><Dextrose><Diabetes Mellitus><Differences between sexes><Differs between sexes><Disturbance in cognition><Drugs><Epidemiology><Glucose><Glycated Hemoglobins><Glycosylated Hemoglobin><Goals><Groups at risk><Health><Health Policy><Hemorrhage><High Prevalence><Human><Hypertension><Impaired cognition><Incidence><Individual><Intervention><Intervention Strategies><Intervention Trial><Interventional trial><Ischemia><Ischemic Stroke><Knowledge><LDL><LDL Cholesterol><LDL Cholesterol Lipoproteins><LDL Lipoproteins><Lead><Lipids><Low Density Lipoprotein Cholesterol><Low-Density Lipoproteins><Measurement><Measures><Medication><Methods><Mission><Modeling><Modern Man><NIH><National Institutes of Health><Outcome><Participant><Pb element><People at risk><Persons at risk><Pharmaceutical Preparations><Policies><Population Heterogeneity><Populations at Risk><Preventative intervention><Prevention><Prevention approach><Primary Senile Degenerative Dementia><Prospective cohort><Public Health><Public Policy><Race><Races><Research><Risk><Risk Factors><Risk Reduction><Sample Size><Science><Sex Differences><Sexual differences><Specific qualifier value><Specified><Stroke><Subgroup><Testing><Translating><Treatment Factor><United States National Institutes of Health><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><adjudication><adjudicative process and procedure><adulthood><after stroke><alzheimer risk><beta-Lipoprotein Cholesterol><beta-Lipoproteins><biologic><blood loss><brain attack><brain health><cardiovascular disease risk><cardiovascular disorder><cardiovascular disorder risk><cerebral vascular accident><cerebrovascular accident><chronic disorder><clinical care><clinical practice><cognitive decline after stroke><cognitive decline in stroke><cognitive dysfunction><cognitive dysfunction after stroke><cognitive dysfunction in stroke><cognitive impairment after stroke><cognitive impairment in stroke><cognitive loss><cohort><computational simulation><computerized simulation><cost><dementia after stroke><dementia risk><design><designing><developmental><diabetes><differences due to race><differences in race><differs by race><differs in race><disability><diverse populations><driving><drug/agent><effective therapy><effective treatment><epidemiologic><epidemiological><health care policy><healthcare policy><heavy metal Pb><heavy metal lead><heterogeneous population><high blood pressure><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><improved><innovate><innovation><innovative><intervention design><intervention for prevention><interventional strategy><model-based simulation><models and simulation><novel><older adult><older adulthood><population diversity><post stroke><post stroke cognitive decline><post stroke cognitive dysfunction><post stroke cognitive impairment><post stroke dementia><poststroke><poststroke cognitive decline><poststroke cognitive dysfunction><poststroke cognitive impairment><poststroke dementia><prevention intervention><preventional intervention strategy><preventive intervention><primary degenerative dementia><public health priorities><race based differences><race differences><race related differences><racial><racial background><racial difference><racial origin><racially different><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><risk factor for dementia><risk for dementia><risk-reducing><senile dementia of the Alzheimer type><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><stroke event><stroke survivor><stroked><strokes><therapy design><treatment design><trial design><vascular><vascular contributions><vascular risk factor>