The Association of Body Mass Index with Cognition and Alzheimer’s Disease Biomarkers in the Elderly with Different Cognitive Status: A Study from the Alzheimer’s Disease Neuroimaging Initiative Database

Background: The association of body mass index (BMI) with cognition and Alzheimer’s disease (AD) biomarkers of the elderly remains inconclusive. Objective: To investigate the relationship between BMI and cognition as well as AD biomarkers in the elderly with different cognitive status. Methods: Participants with cognitively normal (CN) were included as the CN group. Participants with mild cognitive impairment and mild dementia were included as the cognitive impairment (CI) group. The relationship between BMI and AD biomarkers (cerebrospinal fluid Aβ42 and p-tau181, hippocampal volume [HV]), global cognition (Mini-Mental State Examination [MMSE]), memory, and executive function were explored. Results: In the CI group, BMI was associated with MMSE (β= 0.03, p = 0.009), Aβ42 (β= 0.006, p = 0.029), p-tau181/Aβ42 ratio (β= -0.001, p = 0.011), and HV (β= 0.05, p < 0.001). However in the CN group, BMI exhibited associations with p-tau181 (β= 0.012, p = 0.014) and memory composite score (β= -0.04, p = 0.038), but not with p-tau181/Aβ42 ratio and HV. Moreover, mediation analysis showed that in the CI group, the positive effect of BMI on HV and MMSE score was partially mediated by diastolic blood pressure. Conclusion: The association of BMI with cognition and AD biomarkers varies across different cognitive status. In particular, a lower BMI was associated with worse cognition, higher Aβ burden, and lower HV in individuals with CI. Clinical practice should strengthen the monitoring and management of BMI in patients with AD.