title: The identification of cognitive subtypes in Alzheimer's disease dementia using latent class analysis.
abstract: OBJECTIVE
  Alzheimer's disease (AD) is a heterogeneous disorder with complex underlying neuropathology that is still not completely understood. For better understanding of this heterogeneity, we aimed to identify cognitive subtypes using latent class analysis (LCA) in a large sample of patients with AD dementia. In addition, we explored the relationship between the identified cognitive subtypes, and their demographical and neurobiological characteristics.
  
  
  METHODS
  We performed LCA based on neuropsychological test results of 938 consecutive probable patients with AD dementia using Mini-Mental State Examination as the covariate. Subsequently, we performed multinomial logistic regression analysis with cluster membership as dependent variable and dichotomised demographics, APOE genotype, cerebrospinal fluid biomarkers and MRI characteristics as independent variables.
  
  
  RESULTS
  LCA revealed eight clusters characterised by distinct cognitive profile and disease severity. Memory-impaired clusters-mild-memory (MILD-MEM) and moderate-memory (MOD-MEM)-included 43% of patients. Memory-spared clusters mild-visuospatial-language (MILD-VILA), mild-executive (MILD-EXE) and moderate-visuospatial (MOD-VISP) -included 29% of patients. Memory-indifferent clusters mild-diffuse (MILD-DIFF), moderate-language (MOD-LAN) and severe-diffuse (SEV-DIFF) -included 28% of patients. Cognitive clusters were associated with distinct demographical and neurobiological characteristics. In particular, the memory-spared MOD-VISP cluster was associated with younger age, APOE e4 negative genotype and prominent atrophy of the posterior cortex.
  
  
  CONCLUSIONS
  Using LCA, we identified eight distinct cognitive subtypes in a large sample of patients with AD dementia. Cognitive clusters were associated with distinct demographical and neurobiological characteristics.
authors.affiliation: Department of Neurology, Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Nienke M E
authors.initials: NM
authors.lastname: Scheltens
authors.affiliation: Department of Epidemiology and Biostatistics, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Francisca
authors.initials: F
authors.lastname: Galindo-Garre
authors.affiliation: Department of Neurology, Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.affiliation: Department of Neurology, Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Annelies E
authors.initials: AE
authors.lastname: van der Vlies
authors.affiliation: Department of Neurology, Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lieke L
authors.initials: LL
authors.lastname: Smits
authors.affiliation: Department of Medical Psychology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Teddy
authors.initials: T
authors.lastname: Koene
authors.affiliation: Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.affiliation: Department of Neurology, Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Neurology, Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Epidemiology and Biostatistics, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
mesh_terms: D000368:Aged; D000375:Aging / Q000523:psychology; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000150:complications / Q000175:diagnosis* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000150:complications / Q000175:diagnosis* / Q000523:psychology*; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015233:Models, Statistical; D059906:Neuroimaging; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: ALZHEIMER'S DISEASE; COGNITION; COGNITIVE NEUROPSYCHOLOGY; DEMENTIA; STATISTICS