title: Anatomical heterogeneity of Alzheimer disease: based on cortical thickness on MRIs.
abstract: OBJECTIVE
  Because the signs associated with dementia due to Alzheimer disease (AD) can be heterogeneous, the goal of this study was to use 3-dimensional MRI to examine the various patterns of cortical atrophy that can be associated with dementia of AD type, and to investigate whether AD dementia can be categorized into anatomical subtypes.
  
  
  METHODS
  High-resolution T1-weighted volumetric MRIs were taken of 152 patients in their earlier stages of AD dementia. The images were processed to measure cortical thickness, and hierarchical agglomerative cluster analysis was performed using Ward's clustering linkage. The identified clusters of patients were compared with an age- and sex-matched control group using a general linear model.
  
  
  RESULTS
  There were several distinct patterns of cortical atrophy and the number of patterns varied according to the level of cluster analyses. At the 3-cluster level, patients were divided into (1) bilateral medial temporal-dominant atrophy subtype (n = 52, ∼ 34.2%), (2) parietal-dominant subtype (n = 28, ∼ 18.4%) in which the bilateral parietal lobes, the precuneus, along with bilateral dorsolateral frontal lobes, were atrophic, and (3) diffuse atrophy subtype (n = 72, ∼ 47.4%) in which nearly all association cortices revealed atrophy. These 3 subtypes also differed in their demographic and clinical features.
  
  
  CONCLUSIONS
  This cluster analysis of cortical thickness of the entire brain showed that AD dementia in the earlier stages can be categorized into various anatomical subtypes, with distinct clinical features.
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Young
authors.initials: Y
authors.lastname: Noh
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Seun
authors.initials: S
authors.lastname: Jeon
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville. dukna@skku.edu ljm@hanyang.ac.kr.
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Seo
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Geon Ha
authors.initials: GH
authors.lastname: Kim
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Hanna
authors.initials: H
authors.lastname: Cho
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Byoung Seok
authors.initials: BS
authors.lastname: Ye
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Cindy W
authors.initials: CW
authors.lastname: Yoon
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Juhee
authors.initials: J
authors.lastname: Chin
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Kee Hyung
authors.initials: KH
authors.lastname: Park
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Heilman
authors.affiliation: From the Department of Neurology (Y.N., K.H.P.), Gachon University Gil Medical Center, Incheon; Department of Biomedical Engineering (S.J., J.M.L.), Hanyang University, Seoul; Department of Neurology (S.W.S., H.J.K., J.C., D.L.N.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (G.H.K.), Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; Department of Neurology (H.C.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (B.S.Y.), Yonsei University College of Medicine, Seoul; Department of Neurology (C.W.Y.), Inha University Hospital, Inha University School of Medicine, Incheon, Korea; and Department of Neurology (K.M.H.), University of Florida and Veterans Affairs Medical Center, Gainesville. dukna@skku.edu ljm@hanyang.ac.kr.
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000145:classification / Q000473:pathology*; D001931:Brain Mapping / Q000145:classification / Q000379:methods; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged