Neuropsychiatric symptoms (NPS) are a risk factor for cognitive impairment and are associated with cortical β-amyloid (Aβ) 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+) Aβ deposition. We also investigated whether combined presence of MCI and amyloid positivity (MCI/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 11C-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 ε4 genotype status. The sample included 997 CU/A-, 446 CU/A+, 78 MCI/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 MCI/A+ participants. In conclusion, MCI with Aβ burden of the brain is associated with an increased risk of having NPS as compared to MCI without Aβ burden. This implies that the underlying Alzheimer's disease biology (i.e., cerebral Aβ amyloidosis) may drive both cognitive and psychiatric symptoms.

Department of Health Sciences Research Mayo Clinic Rochester MN USA

Department of Neurology Mayo Clinic Rochester MN USA

Department of Neurology Mayo Clinic Scottsdale AZ USA

Department of Psychiatry and Psychology Mayo Clinic Rochester MN USA

Department of Psychiatry and Psychology Mayo Clinic Scottsdale AZ USA

Department of Radiology Mayo Clinic Rochester MN USA

F Hoffmann La Roche Ltd Basel Switzerland

Institute of Sports and Sports Science Karlsruhe Institute of Technology Karlsruhe Germany

International Clinical Research Center St Anne Hospital Brno Czech Republic

Translational Neuroscience and Aging Laboratory Mayo Clinic Scottsdale AZ USA

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A longitudinal investigation of Aβ, anxiety, depression, and mild cognitive impairment

Investigating cognition in midlife

Association of Cortical and Subcortical β-Amyloid With Standardized Measures of Depressive and Anxiety Symptoms in Adults Without Dementia