title: Multiple pathologies are common in Alzheimer patients in clinical trials.
abstract: OBJECTIVE
  To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology.
  
  
  METHODS
  We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology.
  
  
  RESULTS
  Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02).
  
  
  CONCLUSIONS
  While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.
authors.affiliation: Department of Medicine, Faculty of Medicine, University of British Columbia.
authors.forename: B W
authors.initials: BW
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Lu
authors.forename: I R A
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: M
authors.initials: M
authors.lastname: Assaly
authors.forename: C
authors.initials: C
authors.lastname: Jacova
authors.forename: P E
authors.initials: PE
authors.lastname: Lee
authors.forename: B L
authors.initials: BL
authors.lastname: Beattie
authors.forename: G Y R
authors.initials: GY
authors.lastname: Hsiung
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D001344:Autopsy; D002986:Clinical Trials as Topic / Q000379:methods*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D015140:Dementia, Vascular / Q000150:complications / Q000473:pathology; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies