Thigh Fat to Muscle Ratio on MRI is Related to Alzheimer’s Disease Neurodegeneration in Midlife Obesity

Motivation: This study addresses the need for better indicators of metabolic health and cognitive decline, moving beyond BMI to assess midlife obesity's impact on brain health, particularly in relation to Alzheimer disease (AD). Goal(s): To explore the relationship between thigh fat-to-muscle ratio (FMR) and brain cortical thickness, assessing FMR's potential as an early risk indicator for AD. Approach: We examined relationships between FMR and cortical thickness in AD-related brain regions, both derived from MRI, controlling for age, sex, and multiple comparisons. Results: Higher FMR was correlated with increased BMI and insulin resistance and reduced cortical thickness in multiple brain regions associated with AD. Impact: This study demonstrates that thigh FMR may serve as a predictive risk indicator for AD, enabling early identification of individuals at risk. This insight encourages targeted interventions to modify FMR, potentially delaying neurodegeneration and improving cognitive outcomes.