Effect of diabetes and AD pathology on brain imaging and cognition in Latino adults

Abstract Type II diabetes mellitus (T2DM) increases the risk for developing Alzheimer’s Disease (AD), but the mechanisms are not fully understood. To reduce the risk for cognitive decline in those with T2DM and to identify possible intervention targets, it is imperative to understand how T2DM affects the brain and cognition. Our overall goal is to gain an understanding of how metabolic and Alzheimer’s risk relate to brain measures and cognition in 200 Northern American Latino middle-aged adults, an understudied group that is at higher risk for both T2DM and AD compared with non-Latino Whites. We will: 1) Evaluate regional brain integrity (structural, functional, and vascular) in those with and without T2DM and as related to metabolic blood markers and AD pathology risk as indicated by plasma ptau181 level 2) Evaluate the changes in cerebral blood flow, vascular reactivity, and functional connectivity between fasting baseline and 2 hours after 75 grams of glucose ingestion and relate those changes to changes in metabolic markers to gain a mechanistic understanding of how metabolic risk affects the brain’s functional and vascular response to glucose ingestion, and 3) Identify brain measures of neurovascular function (cerebrovascular reactivity, functional connectivity, cerebral blood flow, and blood brain barrier permeability) that predict cognitive decline and brain deficits over 2 years and investigate their relationship to metabolic function and AD pathology. There are ongoing efforts to repurpose diabetes medications into cognition clinical trials. Achieving our aims will provide insights into the mechanisms underlying cognitive decline in T2DM patients with and without AD pathology, and provide brain imaging biomarkers to guide potential interventions.