Brain Regional Glucose Metabolism, Neuropsychiatric Symptoms and the Risk of Incident Mild Cognitive Impairment: the Mayo Clinic Study of Aging

Abstract Objective : We conducted a prospective cohort study to examine the risk of incident mild cognitive impairment (MCI) as predicted by baseline neuropsychiatric symptoms (NPS) and brain regional glucose metabolic dysfunction. Methods : 1363 cognitively unimpaired (CU) individuals (52.8% males) aged ≥ 50 years were followed for a median of 4.8 years to the outcome of incident MCI. NPS were assessed using Beck Depression and Anxiety Inventories (BDI-II, BAI) and Neuropsychiatric Inventory Questionnaire. Glucose hypometabolism was measured by FDG-PET and defined as SUVR ≤ 1.47 in regions typically affected in Alzheimer's disease. Cox proportional hazards models were adjusted for age, sex, education and APOE e4 status. Results : Participants with regional glucose hypometabolism and depression (BDI-II ≥ 13) had a more than threefold increased risk of incident MCI (HR [95% CI], 3.66 [1.75, 7.65], p Conclusion : Combined presence of NPS with regional glucose hypometabolism is associated with an increased risk of incident MCI, with FDG-PET appearing to be a stronger driving force of cognitive decline than NPS.