title: Progression of Extrapyramidal Signs in Alzheimer's Disease: Clinical and Neuropathological Correlates.
abstract: BACKGROUND
  Extrapyramidal signs (EPS) are frequent in Alzheimer's disease (AD) and core manifestation of related diseases, i.e., dementia with Lewy bodies and Parkinson's disease; furthermore, Lewy bodies and AD-type pathology occur in all three conditions.
  
  
  OBJECTIVE
  To identify clusters of EPS progression over time and their clinical and neuropathological correlates.
  
  
  METHODS
  3,502 AD patients with longitudinal assessment from the National Alzheimer's Coordinating Center database were included; 394 provided neuropathological data. k-means algorithm was employed to identify clusters of EPS progression and those were compared in terms of cognitive profile, neuropsychiatric features and neuropathological findings.
  
  
  RESULTS
  Three clusters of EPS progression were identified: no/low (n = 1,583), medium (n = 1,259), and high (n = 660) EPS burden. Compared to those with no/low and medium EPS, those with high EPS had greater cognitive and neuropsychiatric impairment, specifically hallucinations. Despite similar AD-pathology across the three clusters, the high EPS cluster had a significantly number of subjects diagnosed with dementia with Lewy bodies.
  
  
  CONCLUSIONS
  Cluster analysis of EPS progression over time identified different subgroups of AD patients with distinct clinical and neuropathological features.
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.|Sergievsky Center, College of Physiciansand Surgeons, Columbia University New York, NY, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tosto
authors.affiliation: National Alzheimer's Coordinating Center, University of Washington, WA, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Monsell
authors.affiliation: National Alzheimer's Coordinating Center, University of Washington, WA, USA.|Department of Epidemiology, University of Washington, WA, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Hawes
authors.affiliation: Department of Neurology and Psychiatry, University "Sapienza", Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bruno
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.|Sergievsky Center, College of Physiciansand Surgeons, Columbia University New York, NY, USA.|Department of Neurology, College of Physiciansand Surgeons, Columbia University and the New York, Presbyterian Hospital, New York, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
mesh_terms: D000368:Aged; D000465:Algorithms; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D016000:Cluster Analysis; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D012720:Severity of Illness Index
keywords: Alzheimer’s disease; K-means clustering; Lewy bodies; extrapyramidal signs; longitudinal studies