期刊
ALZHEIMERS & DEMENTIA
卷 13, 期 11, 页码 1226-1236出版社
WILEY
DOI: 10.1016/j.jalz.2017.03.002
关键词
Alzheimer's disease; Cognition; Heterogeneity; Subtypes; Atypical; Neuropsychology
资金
- Alzheimer Nederland
- Stichting VUmc Fonds
- Stichting Dioraphte
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc
- Cogstate
- Eisai Inc
- Elan Pharmaceuticals, Inc
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- company Genentech, Inc
- Fujirebio
- GE Healthcare
- IXICO Ltd
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC
- Lumosity
- Lundbeck
- Merck Co, Inc
- Meso ScaleDiagnostics, LLC
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- German Federal Ministry of Education and Research (BMBF) [01GI0420]
Introduction: Patients with Alzheimer's disease (AD) show heterogeneity in profile of cognitive impairment. We aimed to identify cognitive subtypes in four large AD cohorts using a data-driven clustering approach. Methods: We included probable AD dementia patients from the Amsterdam Dementia Cohort (n = 496), Alzheimer's Disease Neuroimaging Initiative (n = 376), German Dementia Competence Network (n = 521), and University of California, San Francisco (n = 589). Neuropsychological data were clustered using nonnegative matrix factorization. We explored clinical and neurobiological characteristics of identified clusters. Results: In each cohort, a two-clusters solution best fitted the data (cophenetic correlation > 0.9): one cluster was memory-impaired and the other relatively memory spared. Pooled analyses showed that the memory-spared clusters (29%-52% of patients) were younger, more often apolipoprotein E (APOE) epsilon 4 negative, and had more severe posterior atrophy compared with the memory-impaired clusters (all P < .05). Conclusions: We could identify two robust cognitive clusters in four independent large cohorts with distinct clinical characteristics. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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