title: Progression to dementia in memory clinic patients without dementia: a latent profile analysis.
abstract: OBJECTIVE
  To identify the existence of discrete cognitive subtypes among memory clinic patients without dementia and test their prognostic values.
  
  
  METHODS
  In a retrospective cohort study of 635 patients without dementia visiting the Alzheimer centers in Maastricht or Amsterdam, latent profile analysis identified cognitive subtypes based on immediate and delayed memory recall, delayed recognition, information-processing speed, attention, verbal fluency, and executive functions. Time to dementia was tested in weighted Cox proportional hazard models adjusted for confounders.
  
  
  RESULTS
  Five latent classes represented participants with high-normal cognition (15%), low-normal cognition (37%), primary memory impairment in recall (MI) (36%), memory impairment in recall and recognition (MI+) (5%), and primary nonmemory impairment (NMI) (6%). Compared with low-normal cognition, participants with NMI had the highest risk of dementia (hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.46-10.18) followed by MI (HR = 3.05, 95% CI = 2.09-4.46) and MI+ (HR = 3.26, 95% CI = 1.72-6.17), while participants with high-normal cognition had the lowest risk (HR = 0.24, 95% CI = 0.07-0.80). Subtypes further showed differential relationships with dementia types, with MI and MI+ most often converting to Alzheimer-type dementia and NMI to other forms of dementia.
  
  
  CONCLUSIONS
  Cognitive subtypes can be empirically identified in otherwise heterogeneous samples of memory clinic patients and largely confirm current strategies to distinguish between amnestic and nonamnestic impairment. Studying more homogeneous cognitive subtypes may improve understanding of disease mechanisms and outcomes.
authors.affiliation: From the Alzheimer Center Limburg (S.K., R.H., P.-J.V., P.A., F.R.J.V., I.R.), School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht; and Alzheimer Center & Department of Neurology (N.S., Y.A.L.P., W.M.v.d.F., P.S., P.-J.V.), Department of Medical Psychology (T.K.), Neuroscience Campus Amsterdam, and Department Epidemiology & Biostatistics (W.M.v.d.F.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Köhler
authors.forename: Renske
authors.initials: R
authors.lastname: Hamel
authors.forename: Nicole
authors.initials: N
authors.lastname: Sistermans
authors.forename: Ted
authors.initials: T
authors.lastname: Koene
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Pieter-Jelle
authors.initials: PJ
authors.lastname: Visser
authors.forename: Pauline
authors.initials: P
authors.lastname: Aalten
authors.forename: Frans R J
authors.initials: FR
authors.lastname: Verhey
authors.forename: Inez
authors.initials: I
authors.lastname: Ramakers
mesh_terms: D000368:Aged; D001288:Attention; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology*; D015331:Cohort Studies; D003704:Dementia / Q000175:diagnosis* / Q000209:etiology; D018450:Disease Progression; D056344:Executive Function; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology*; D011939:Mental Recall; D008875:Middle Aged; D009483:Neuropsychological Tests; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D021641:Recognition, Psychology; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed