Abstract

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.

Highlights

  • Neuropsychiatric symptoms (NPS) are risk factors for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia[1,2,3,4,5]

  • Cortical amyloid deposition among cognitively normal[6,7,8] or impaired participants[9,10,11,12,13,14], these studies have been limited by small sample sizes, have not determined whether the associations between NPS and elevated brain amyloid differ by cognitive status (cognitively unimpaired (CU) vs. MCI), or have not conducted subanalyses among persons with amnestic MCI. aMCI coupled with amyloid positivity is considered the typical prodromal stage of dementia due to AD15

  • Here we report that community-dwelling older persons with coexistence of MCI and elevated brain amyloid deposition had significantly higher odds of having NPS as Dependent N Independent N odds ratios (OR) p variable variable

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Summary

Introduction

Neuropsychiatric symptoms (NPS) are risk factors for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia[1,2,3,4,5]. Association between NPS and cognitive/amyloid status After adjusting for age, sex, education, and APOE ε4 carrier status, the odds of having any NPS as measured by NPI-Q (i.e. depression, anxiety, apathy, irritability, nighttime behavior, any NPS, and any non-psychotic NPS), depression (BDI-II ≥ 13), or anxiety (BAI ≥ 8, BAI ≥ 10) were significantly increased for the MCI/A+ group as compared to the reference group (CU/A−) for all variables (Table 3).

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Conclusion
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