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

项目摘要/摘要 阿尔茨海默病(AD)和酒精使用障碍(AUD)是两种疾病，它们的成本都很高 生活质量下降，死亡率高，预后差。最近的证据表明，澳元是一种危险因素 虽然这两种疾病之间的确切关系尚不清楚。这项拟议的研究旨在澄清 通过确定哪些功能性神经病理与AUD的认知功能下降相关来确定这种关系 以及轻度认知障碍(MCI)，这是一种经常出现在痴呆症之前的认知病理。这 项目将收集来自澳大利亚大学参与者的静息和基于任务的功能磁共振数据，并使用来自MCI和 健康对照组(HC)。这两种任务范式由情景记忆编码任务和空间记忆编码任务组成 工作记忆任务。休眠状态数据将被用来提取默认模式网络、插曲 记忆编码任务数据将被用来提取情节记忆网络，而空间工作网络将被用于提取情景记忆网络。 记忆任务数据将被用于提取空间工作记忆网络。图论度量学将 用来表征蒙特利尔测量的与认知障碍相关的连接体特征 认知评估(MoCA)评分。主要的假设是插曲的图论特征 健康对照组的记忆网络和/或默认模式网络将显示AUD和 MCI组，这些改变与MoCA评分相关。探索性的假设是 空间工作记忆网络的图论分数将与AUD的MoCA分数相关联 研究对象。如果这些假设得到证实，可能会提供初步证据，表明澳元增加了患糖尿病的风险 AD是由高危个体先前存在的轻度缺陷复合所致的认知障碍。 这些证据可以通过阐明新的治疗靶点来指导未来对这两种疾病的治疗 可以阻止或减缓认知能力下降的进程。

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.