Document text
Principal Investigator: L Elliot Elliot Hong
Organization: UNIVERSITY OF MARYLAND BALTIMORE
Fiscal Year: 2024
Award: $770,374
Funding agency: National Institute of Neurological Disorders and Stroke
Project Summary / Abstract
Vascular biology and white matter may be some of the key junctures that harbor early risk mechanisms that
precipitate vascular contributions to cognitive impairment and Alzheimer's disease. This process may start as
early as adolescence and young adulthood, and through our lifespan. While cardiovascular impacts on white
matter health are well-established, our understanding of the lifetime course and the associated mechanisms
are less clear. Our efforts aim to identify the earliest possible vascular biomarkers and risk factors for abnormal
white matter changes for the corresponding cognitive declines. Cardiovascular-brain studies typical focus on
structural imaging changes that are difficult to reverse. We hypothesize that white matter lifespan changes can
be more sensitively tracked by combining standard structural imaging techniques with state-of-the-art
connectome era multimodal imaging. The goal is to uncover novel vascular - white matter mechanisms and
biomarkers that provide early warnings before the irreversible structural changes occur. The proposal builds
upon the productivity of the Amish Connectome Project as baseline data, and leverages the collaboration
between our brain imaging and cardiovascular medicine groups. The Old Order Amish/Mennonite population
has a more uniform genetic profile, rural lifestyle and low alcohol and tobacco use that greatly reduce
uncontrollable variability, thus providing a particularly advantageous platform to study the vascular
mechanisms on white matter. Cerebral white matter will also be studied in the context of predicting white
matter vulnerability to Alzheimer's disease. Tracking when the aberrant vascular – white matter coupling
occurs may provide insights into the timing and mode for more effective prevention. This proposal is
responsive to the new NIH Inclusion Across the Lifespan policy. If successful, the proposed study should
strongly support the prevention goal highlighted in the National Alzheimer's Project Act, which supports
increased public research to prevent the onset of and develop effective treatments for AD by 2025. Prevention
programs can be benefited by more nuanced understanding of the pathways connecting early vascular
changes to irreversible white matter changes. Therefore, we propose to use cutting-edge white matter imaging
that is informative of the underlying mechanisms, combined with standard but state-of-the-art vascular
assessments, to study the interaction between vascular and white matter changes across lifespan.
Terms: <12-20 years old><3-D><3-Dimensional><3D><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><Active Follow-up><Adolescence><Age><Age-associated cognitive decline><Age-associated memory impairment><Age-related cognitive decline><Aged 65 and Over><Aging><Alcohol Drinking><Alcohol consumption><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer risk factor><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimer's disease risk><Alzheimers Dementia><Amentia><Amish><Anatomic Sites><Anatomic structures><Anatomy><Automobile Driving><Benign senescent forgetfulness><Biological Markers><Biology><Blood Vessels><Brain><Brain Nervous System><Brain imaging><Brain region><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Cerebrovascular Circulation><Cerebrum><Clinical><Cognition><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Cohort Effect><Collaborations><Communities><Coupling><DWI (diffusion weighted imaging)><DWI-MRI><Data><Dementia><Development><Diffusion MRI><Diffusion Magnetic Resonance Imaging><Diffusion Weighted MRI><Diffusion weighted imaging><Diffusion-weighted Magnetic Resonance Imaging><Disturbance in cognition><Dysfunction><Encephalon><Endothelium><EtOH drinking><EtOH use><Family><Functional disorder><Generation Effect><Genetic><Goals><Health><Heart Vascular><Image><Imaging Procedures><Imaging Technics><Imaging Techniques><Impaired cognition><Individual><Label><Lesion><Life Style><Lifestyle><Measures><Mediating><Medicine><Mennonite><Modeling><Multimodal Imaging><Multivariate Analyses><Multivariate Analysis><NIH><National Institutes of Health><Natural History><Neurologic><Neurological><Organ><Pathogenesis><Pathway interactions><Patients><Pattern><Perfusion><Physiologic pulse><Physiopathology><Policies><Population><Predicting Risk><Prevention><Prevention program><Primary Senile Degenerative Dementia><Process><Productivity><Pulse><Regional Disease><Research><Risk><Risk Factors><Risk Reduction><Rural><Scientist><Specificity><Structure><Testing><Tobacco Consumption><Tobacco use><United States National Institutes of Health><Vascular Cognitive Impairment><Vascular Endothelium><Vasodilatation><Vasodilation><Vasorelaxation><White Matter Hyperintensity><abeta accumulation><abeta aggregation><above age 65><active followup><adolescence (12-20)><adult youth><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age associated><age associated decline><age associated effects><age associated memory decline><age correlated><age dependent><age dependent decline><age effect><age linked><age of 65 years onward><age related><age related cognitive deficit><age related cognitive impairment><age related decline><age related effects><age related memory dysfunction><age specific><age-induced cognitive decline><age-related decline in cognition><age-related decline in cognitive function><aged 65 and greater><aged 65+><aged brain><aged ≥65><ages><aging brain><aging effect><alcohol ingestion><alcohol intake><alcohol product use><alcohol use><alcoholic beverage consumption><alcoholic drink intake><allostatic load><alzheimer risk><amyloid beta accumulation><amyloid beta aggregation><amyloid β accumulation><amyloid β aggregation><arterial spin labeling><arterial spin tagging><arterial stiffening><arterial stiffness><artery stiffening><artery stiffness><aβ accumulation><aβ aggregation><bio-markers><biologic marker><biomarker><blood flow in brain><brain blood circulation><brain blood flow><brain visualization><cardiometabolic risk><cardiovascular risk><cardiovascular risk factor><cerebral><cerebral blood flow><cerebral circulation><cerebrocirculation><cerebrovascular blood flow><circulatory system><cognitive dysfunction><cognitive loss><cohort><connectome><dMRI><decline with age><developmental><diffusion tensor imaging><driving><effective therapy><effective treatment><endothelial dysfunction><ethanol consumption><ethanol drinking><ethanol ingestion><ethanol intake><ethanol product use><ethanol use><follow up><follow-up><followed up><followup><forecasting risk><human old age (65+)><image-based method><imaging><imaging method><imaging modality><impact of age><indexing><influence of age><insight><life span><lifespan><multi-modal imaging><multi-modality imaging><multimodality imaging><neural imaging><neuro-imaging><neuroimaging><neurological imaging><novel><old age><over 65 years><pathophysiology><pathway><predict risk><predict risks><predicted risk><predicted risks><predicting risks><predictive risk><predicts risk><prevent><preventing><primary degenerative dementia><reactive hyperemia><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><risk prediction><risk predictions><risk-reducing><senile dementia of the Alzheimer type><structural imaging><substantia alba><three dimensional><tobacco product use><vascular><vascular and cognitive impairment><vascular cognition impairment><vascular cognitive decline><vascular cognitive disease><vascular cognitive dysfunction><vascular contributions to cognitive impairment><vascular related cognitive decline><vascular related cognitive impairment><white matter><white matter change><young adult><young adulthood><≥65 years>