OBJECTIVE: The authors 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: About 1,363 cognitively unimpaired 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 and Neuropsychiatric Inventory Questionnaire. Glucose hypometabolism was measured by fluorodeoxyglucose positron emission tomography and defined as standardized uptake value ratio ≤ 1.47 in regions typically affected in Alzheimer disease. Cox proportional hazards models were adjusted for age, sex, education, and APOE ε4 status. RESULTS: Participants with regional glucose hypometabolism and depression (Beck Depression Inventory-II ≥13) had a more than threefold increased risk of incident MCI (hazard ratio [95% confidence interval], 3.66 [1.75, 7.65], p <0.001, χ2 = 11.83, degree of freedom [df] = 1) as compared to the reference group (normal regional glucose metabolism and no depression), and the risk was also significantly elevated (7.21 [3.54, 14.7], p <0.001, χ2 = 29.68, df = 1) for participants with glucose hypometabolism and anxiety (Beck Anxiety Inventory ≥10). Having glucose hypometabolism and ≥1 NPS (3.74 [2.40, 5.82], p <0.001, χ2 = 34.13, df = 1) or ≥2 NPS (3.89 [2.20, 6.86], p <0.001, χ2 = 21.92, df = 1) increased the risk of incident MCI by more than three times, and having ≥3 NPS increased the risk by more than four times (4.12 [2.03, 8.37], p <0.001, χ2 = 15.39, df = 1). CONCLUSION: Combined presence of NPS with regional glucose hypometabolism is associated with an increased risk of incident MCI, with fluorodeoxyglucose positron emission tomography appearing to be a stronger driving force of cognitive decline than NPS.

Department of Health Sciences Research Mayo Clinic Rochester Rochester MN

Department of Health Sciences Research Mayo Clinic Rochester Rochester MN; Department of Neurology Mayo Clinic Rochester Rochester MN

Department of Health Sciences Research Mayo Clinic Rochester Rochester MN; Department of Psychiatry and Psychology Mayo Clinic Rochester Rochester MN

Department of Health Sciences Research Mayo Clinic Rochester Rochester MN; Institute of Sports and Sports Science Karlsruhe Institute of Technology Karlsruhe Germany

Department of Neurology Barrow Neurological Institute Phoenix AZ

Department of Neurology Mayo Clinic Rochester Rochester MN

Department of Radiology Mayo Clinic Rochester Rochester MN

International Clinical Research Center St Anne Hospital Brno Czech Republic

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Interactions Between Neuropsychiatric Symptoms and Alzheimer's Disease Neuroimaging Biomarkers in Predicting Longitudinal Cognitive Decline