Structural Brain Correlates With Appetite and Eating Disturbances Across the Alzheimer Disease Spectrum

Introduction: Neuropsychiatric symptoms are integral features of Alzheimer disease (AD) and may precede cognitive impairment. Appetite and eating disturbances are common across the AD spectrum. Methods: We analyzed 7223 participants from the National Alzheimer’s Coordinating Center with Uniform Data Set assessments and MRI. Appetite and eating disturbances were assessed using the Neuropsychiatric Inventory Questionnaire. Cross-sectional associations with brain volumes were examined using multivariable regression. Longitudinal analyses among participants without baseline appetite disturbance used discrete-time survival models. Results: Appetite disturbances were present in 9.4% of participants and were associated with greater neuropsychiatric burden and disease severity. Cross-sectionally, lower global gray matter volume showed the most robust association, while regional effects were attenuated after neuropsychiatric adjustment. Longitudinally, baseline brain structure predicted incident appetite disturbance only among cognitively normal participants (OR per SD decrease=0.87). Discussion: Appetite disturbances may reflect diffuse neurodegenerative vulnerability and represent early behavioral markers of Alzheimer-related brain aging.