Cognitive subtypes of probable Alzheimer's disease robustly identified in four cohorts |
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| Institution: | 1. Department of Neurology, Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands;2. Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands;3. Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands;4. Institute of Neurology, University College London, London, UK;5. Institute of Healthcare Engineering, University College London, London, UK;6. Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Centre, Amsterdam, The Netherlands;7. Department of Psychiatry, University of Bonn, Bonn, Germany;8. German Center for Neurodegenerative Diseases, Bonn, Germany;9. Department of Psychiatry, Friedrich-Alexander-University Erlangen, Erlangen, Germany;10. Department of Psychiatry, Charité Berlin, Campus Benjamin Franklin, Berlin, Germany;11. Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA;12. Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands;1. Center for Neuroscience, University of California, Davis, CA 95618, USA;2. Department of Psychology, University of California, Davis, CA 95616, USA;3. Neuroscience Graduate Group, University of California, Davis, CA 95618, USA;4. Physician Scientist Training Program, University of California, Davis, CA 95817, USA;1. Neuroscience Department, University of Southern California, Los Angeles, CA, USA;2. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA;3. Department of Medicine, Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA;4. Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA;5. Division of Epidemiology, Department of Health Research and Policy, Stanford University, Stanford, CA, USA;6. Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA;7. Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA;1. Department of Psychiatry, University of California–San Francisco, San Francisco, CA, USA;2. Department of Neurology and Center for Neuroscience, University of California–Davis, Sacramento, CA, USA;3. Helen Wills Neuroscience Institute, University of California–Berkeley, Berkeley, CA, USA;4. Division of Biostatistics, Department of Public Health Sciences, University of California–Davis, Davis, CA, USA;1. Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa, USA;2. Department of Psychology, Iowa State University, Ames, Iowa, USA;3. Department of Neurology, University of Iowa, Iowa City, Iowa, USA;4. Bryan Alzheimer''s Disease Research Center, Duke University, Durham, North Carolina, USA;5. Zinfandel Pharmaceuticals, Chapel Hill, North Carolina, USA;6. Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, Wisconsin, USA;7. Wisconsin Alzheimer''s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA;8. Department of Health Sciences Research, Mayo Clinic (Rochester), Rochester, Minnesota, USA;9. Wisconsin Alzheimer''s Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA;1. Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA;2. Veterans Affairs San Diego Healthcare System, San Diego, CA, USA;3. San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA;4. Department of Psychology, University of Southern California, Los Angeles, CA, USA;5. Department of Neurology, Drexel University, College of Medicine, Philadelphia, PA, USA;6. Department of Neurology, Boston University, School of Medicine, Boston, MA, USA;7. Framingham Heart Study, Boston University, School of Medicine, Boston, MA, USA;8. Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, USA;1. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden;2. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden;3. Department of Radiology, Karolinska University Hospital, Stockholm, Sweden;4. Department of Neurobiology, Care Sciences, and Society, Centre for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden;5. Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden;6. Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology, and Neuroscience, King''s College London, London, UK |
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| Abstract: | IntroductionPatients 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.MethodsWe 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.ResultsIn 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).ConclusionsWe could identify two robust cognitive clusters in four independent large cohorts with distinct clinical characteristics. |
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| Keywords: | Alzheimer's disease Cognition Heterogeneity Subtypes Atypical Neuropsychology |
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