期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 60, 期 2, 页码 483-493出版社
IOS PRESS
DOI: 10.3233/JAD-160767
关键词
Alzheimer's disease; Alzheimer's Disease Neuroimaging Initiative; apathy; depression; neuropsychiatric inventory; neuropsychiatric symptoms; psychosis
资金
- NIH [P30 AG010129, K01 AG030514]
- Dana Foundation
- Laval University, Quebec City, Canada
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- BioClinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Company
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- F. Hoffmann-La Roche Ltd
- affiliated company Genentech, Inc.
- GE Healthcare
- Innogenetics, N.V.
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Medpace, Inc.
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Synarc Inc.
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- [R01-AG029411]
- [R21-AG029840]
- [P50-AG05134]
- [P50-AG05681]
- [P01-AG003991]
- [U24-RR021382]
- [R01-MH56584]
- [R01-AG030311]
- [DP1OD003312]
Background: An integrative model of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) is lacking. Objective: In this study, we investigated the risk factors, anatomy, biology, and outcomes of NPS in AD. Methods: 181 subjects were included from the Alzheimer's Disease Neuroimaging Study (ADNI). NPS were assessed with the Neuropsychiatric Inventory Questionnaire at baseline and 6 months. NPI > 3 was used as a threshold for NPS positivity. Three NPS courses were characterized: 1) minimal/absent (negative at 0 and 6 months, n = 77); 2) fluctuating (positive only at one time point, n = 53); 3) persistent (positive at both time points, n = 51). We examined the association between NPS course and family history of dementia, personal history of psychiatric disorders, cerebrospinal fluid biomarkers, atrophy patterns, as well as longitudinal cognitive and functional measures at 12 and 24 months (MMSE, CDR-SOB, FAQ). Results: AD subjects with absent, fluctuating, or persistent NPS had similar CSF amyloid-beta and tau levels. AD subjects with minimal/absent NPS had less personal history of psychiatric disorders (35%) than those with fluctuating (57%; p = 0.015) or persistent NPS (47%, not significant). At 24 months, AD subjects with persistent NPS had worse cognitive (MMSE; p = 0.05) and functional (CDR-SOB; p = 0.016) outcomes. Dorsolateral prefrontal atrophy was seen in persistent NPS, but not in fluctuating NPS. Conclusions: Our results suggest that individuals with personal history of psychiatric disorders might be more vulnerable to develop NPS throughout the course of AD. The worst cognitive and functional outcomes associated with NPS in AD underscores the importance of monitoring NPS early in the disease course.
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