AD Supplement to Cerebellar Structure and Function in Alcoholism

Stanford University, Stanford CA

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Abstract

PROJECT SUMMARY ABSTRACT This application is written in response to Program Announcement NOT-AG-18-039 (https://grants.nih.gov/grants/guide/pa-files/PA-18-591.html). The proposed work will extend Specific Aim 2 of the parent award (R37 AA010723), namely, quantifying selective neuroanatomical regions and identifying related functions of networks involving frontocerebellar circuitry, which will now include three groups of men and women: Alzheimer's Disease (AD), Alcohol Use Disorder (AUD), and age- and sex-matched controls. We will quantify in vivo loss of brain tissue, impairment of gait and balance, and cognitive decline in aging, AD and AUD, with neuroimaging, cognitive assessment, and balance platform posturography. AD participants are identified, diagnosed, and genotyped through the Sierra Pacific Mental Health Research and Treatment Dementia Core (MIRECC) and the State of California-funded Stanford/VA Alzheimer Center. Through the program of study conducted with the continuous funding of the parent R37 award, we have found that selective regions of the cerebellum are structurally and functionally vulnerable to aging and alcohol-related decline. With our background in quantitative neuroimaging, cognitive assessment and posturography in aging populations, we propose to apply our methods to men and women with AD in comparison with men and women with AUD and age- and sex-matched aging controls. Quantitative analysis of high-resolution imaging of regional cerebellar and supratentorial brain structures acquired contemporaneously with posturography in addition to cognitive tasks assessing selective frontocerebellar systems will enable the development of patterns and severity levels of brain structural and functional sparing and impairment that are overlapping with and others that are unique to AD and AUD. Study of the tau-based dementia of AD in this context is novel and timely, given a growing literature 1) indicating the involvement of the cerebellum in AD, 2) recognizing accelerated postural instability with advancing AD, thereby enhancing the risk of falls, and 3) suggesting a possible overlap?if not interaction? of AD and AUD. Supplemental Specific Aim To quantify selective neuroanatomical regions and identify related cognitive and motor functions of networks involving frontocerebellar circuitry disrupted in Alzheimer's disease compared with Alcohol Use Disorder and healthy aging.