Impact of obesity on neuropsychiatric symptoms in Alzheimer's disease: Insights from the ADNI cohort

Background Obesity is a major global health issue linked to increased risks of dementia, including Alzheimer's disease (AD). While the association between obesity and neuropsychiatric symptoms (NPS) in AD remains underexplored, identifying these links could aid in weight management in AD patients. Objective This study investigates the relationship between body mass index (BMI) and NPS in AD dementia patients, focusing on the potential mediating role of systemic inflammation. Methods We employed Generalized Additive Models (GAMs) to explore the relationship between BMI and NPS, as measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q). Participants were classified into ideal, overweight, and obese groups based on WHO criteria. Longitudinal analyses assessed the trajectory of NPI-Q scores in different groups over a one-year follow-up. Results BMI significantly affects NPI-Q total scores and specific symptoms, including delusions, hallucinations, agitation/aggression, elation/euphoria, disinhibition, irritability/lability, aberrant motor behavior, nighttime disturbances, and appetite/eating disturbances. Obese patients exhibited higher NPI-Q total scores and greater severity in symptoms such as hallucinations, agitation/aggression, elation/euphoria, apathy/indifference, disinhibition, aberrant motor behavior, and nighttime disturbances. Additionally, CRP and complement C3 were identified as mediators in the relationship between obesity and NPS, highlighting the role of systemic inflammation. Conclusions This study demonstrates that obesity is associated with a heightened burden of NPS in AD dementia patients. The identification of CRP and complement C3 as mediators suggests inflammation plays a crucial role in the association between obesity and NPS. These findings underscore the importance of addressing obesity and its inflammatory consequences in managing NPS among this vulnerable population.