Connectomic Dysfunction Underlying Cognitive Impairment in Alcohol Use Disorder and the Link to Alzheimer’s Disease

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Project Summary/Abstract Alzheimer’s Disease (AD) and Alcohol Use Disorder (AUD) are two disorders that share a high cost of degraded life quality, high mortality, and poor prognosis. Recent evidence suggests that AUD is a risk factor for AD though the exact relationship between the two disorders is unknown. The proposed study aims to elucidate this relationship by determining which functional neuropathologies are associated with cognitive decline in AUD and mild cognitive impairment (MCI), a cognitive pathology which frequently precedes dementia. This project will collect resting and task-based fMRI data from AUD participants and use existing data from MCI and healthy controls (HC). The two task paradigms consist of an episodic memory encoding task and a spatial working-memory task. The resting-state data will be used to extract the default mode network, the episodic memory encoding task data will be used to extract the episodic memory network, and the spatial working- memory task data will be used to extract the spatial working-memory network. Graph-theory metrics will be used to characterize connectome profiles associated with cognitive impairment, as measured by Montreal Cognitive Assessment (MoCA) score. The primary hypotheses are that graph-theory features of the episodic memory network and/or the default mode networks in healthy controls will show alterations in the AUD and MCI group and that these alterations are associated with MoCA score. The exploratory hypothesis is that graph-theory scores of the spatial working-memory network will be associated with MoCA score in AUD subjects. If the hypotheses are confirmed it could provide initial evidence that AUD increases the risk of AD through cognitive impairment that results from compounding mild pre-existing deficits in at-risk individuals. Such evidence could guide future treatments for both disorders by elucidating novel treatment targets which could stop or slow the progression of cognitive decline.