Amyloid-β, Neuropsychiatric Symptoms and the Risk of Incident Mild Cognitive Impairment: A Prospective Cohort Study (S35.003)

Objective: To examine a potential interaction between Aβ and depression/ anxiety on the outcome of incident mild cognitive impairment (MCI). Background: Amyloid-β (Aβ) and neuropsychiatric symptoms (NPS) are independent risk factors for cognitive impairment. However, it remains unclear whether they synergistically interact in further elevating the risk of incident MCI. Methods: We conducted a prospective cohort study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota. We followed 950 cognitively normal participants aged ≥ 50 years for a median of 28 months to the outcome of incident MCI. Participants underwent PiB-PET scans, neuropsychological evaluations and assessments using Beck Depression Inventory II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. We used a global cortical to cerebellar ratio cut-point to classify participants as PiB+ (≥1.4) or PiB- (<1.4). A BDI-II score ≥ 13 was indicative of depression; and we classified anxiety as BAI score ≥ 10. We calculated hazard ratios (HR) and 95[percnt] confidence intervals (95[percnt] CI) using Cox proportional hazards models after adjusting for age, sex and education. Results: Participants who were PiB+ and depressed had a more than 3-fold increased risk of incident MCI (HR [95[percnt] CI], 3.56 [1.46, 8.63]) as compared to the reference group (PiB-, non-depressed). Similarly, participants who were PiB+ and anxious had a more than 5-fold increased risk of incident MCI (HR [95[percnt] CI], 5.38 [2.35, 12.3]) as compared to the reference group (PiB-, non-anxious). A test of positive interaction was significant for Aβ and depression at p=0.032; and for Aβ and anxiety at p=0.034. Conclusions: Aβ and depression or anxiety have a positive synergistic interaction to further elevate the risk of incident MCI. This suggests that interventions that target presymptomatic Alzheimer9s disease biomarkers may need to account for depressive and anxiety symptoms. Disclosure: Dr. Neureiter has nothing to disclose. Dr. Krell-Roesch has nothing to disclose. Dr. Pink has nothing to disclose. Dr. Stokin has nothing to disclose. Dr. Roberts has nothing to disclose. Dr. Mielke has received personal compensation for activities with Lysosomal Therapeutics, Incorporated. Dr. Christianson has nothing to disclose. Dr. Spangehl has nothing to disclose. Dr. Lowe has received personal compensation for activities with Bayer Pharmaceuticals as a consultant. Dr. Jack has received personal compensation for activities with Janssen Research & Development, LLC by providing consulting services. Dr. Jack has received research support from the National Institutes of Health (R01-AG011378, RO1-AG041851, RO1-AG037551. Dr. Knopman has received personal compensation for activities with Lundbeck Pharmaceuticals. Dr. Knopman has received personal compensation in an editorial capacity for Neurology. Dr. Knopman has received research support from Lilly Pharmaceuticals and Ta Dr. Boeve has received personal compensation for activities with Isis Pharmaceuticals. Dr. Boeve has received research support from GE Healthcare and FORUM Pharmaceuticals. Dr. Ronald Petersen received personal compensation from Pfizer, Inc., Janssen Alzheimer9s Immunotherapy. Merck, inc. Roche, Inc. Genentech, Inc. Biogen, Inc. Eli Lilly and Co. as a consultant or speaker. Dr. Geda has nothing to disclose.