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Alzheimers Dement. 2017 Nov;13(11):1226-1236. doi: 10.1016/j.jalz.2017.03.002. Epub 2017 Apr 17.

Cognitive subtypes of probable Alzheimer's disease robustly identified in four cohorts.

Author information

1
Department of Neurology, Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: n.scheltens@vumc.nl.
2
Department of Neurology, Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
3
Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands.
4
Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands; Institute of Neurology, University College London, London, UK; Institute of Healthcare Engineering, University College London, London, UK.
5
Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Centre, Amsterdam, The Netherlands.
6
Department of Psychiatry, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases, Bonn, Germany.
7
Department of Psychiatry, Friedrich-Alexander-University Erlangen, Erlangen, Germany.
8
Department of Psychiatry, Charité Berlin, Campus Benjamin Franklin, Berlin, Germany.
9
Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
10
Department of Neurology, Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

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) ɛ4 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.

KEYWORDS:

Alzheimer's disease; Atypical; Cognition; Heterogeneity; Neuropsychology; Subtypes

PMID:
28427934
PMCID:
PMC5857387
DOI:
10.1016/j.jalz.2017.03.002
[Indexed for MEDLINE]
Free PMC Article

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