Cortical β-amyloid burden, neuropsychiatric symptoms, and cognitive status: the Mayo Clinic Study of Aging

Neuropsychiatric symptoms (NPS) are a risk factor for cognitive impairment and are associated with cortical beta-amyloid (A beta) deposition. We conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging to examine the frequency of NPS among cognitively unimpaired (CU) and mild cognitive impairment (MCI) participants who either have normal (A-) or abnormal (A+) A beta deposition. We also investigated whether combined presence of MCI and amyloid positivity (MCl/A+) is associated with greater odds of having NPS as compared to CU/A- (defined as reference group). Participants were 1627 CU and MCI individuals aged >= 50 years (54% males; median age 73 years). All participants underwent NPS assessment (Neuropsychiatric Inventory Questionnaire (NPI-Q); Beck Depression Inventory II (BDI-II); Beck Anxiety Inventory (BAI)) and C-11-PiB-PET. Participants with an SUVR > 1.42 were classified as A+. We conducted multivariable logistic regression analyses adjusted for age, sex, education, and APOE epsilon 4 genotype status. The sample included 997 CU/A-, 446 CU/A+, 78 MCl/A-, and 106 MCI/A+ persons. For most NPS, the highest frequency of NPS was found in MCI/A+ and the lowest in CU/A-. The odds ratios of having NPS, depression (BDI >= 13), or anxiety (BAI >= 8, >= 10) were consistently highest for MCl/A+ participants. In conclusion, MCI with A beta burden of the brain is associated with an increased risk of having NPS as compared to MCI without A beta burden. This implies that the underlying Alzheimer's disease biology (i.e., cerebral A beta amyloidosis) may drive both cognitive and psychiatric symptoms.