title: Predictors of preclinical Alzheimer disease and dementia: a clinicopathologic study.
abstract: BACKGROUND
  To understand the earliest signs of cognitive decline caused by Alzheimer disease (AD) and other illnesses causing dementia, information is needed from well-characterized individuals without dementia studied longitudinally until autopsy.
  
  
  OBJECTIVE
  To determine clinical and cognitive features associated with the development of AD or other dementias in older adults.
  
  
  METHODS
  Longitudinal study of memory and aging.
  
  
  METHODS
  Alzheimer's Disease Research Center, St Louis, Mo.
  
  
  METHODS
  Clinical Dementia Rating, its sum of boxes, and neuropathologic diagnosis of dementia.
  
  
  METHODS
  Eighty control participants who eventually came to autopsy.
  
  
  RESULTS
  Individuals who did not develop dementia showed stable cognitive performance. Entry predictors of dementia were age, deficits in problem solving as well as memory, slowed psychomotor performance, and depressive features. Minimal cognitive decline occurred prior to dementia diagnosis, after which sharp decline was noted. Even individuals who were minimally cognitively impaired (Clinical Dementia Rating = 0.5) typically had neuropathologic AD at autopsy. Histopathologic AD also was present in 34% of individuals who did not have dementia at death; these individuals without dementia showed an absence of practice effects on cognitive testing.
  
  
  CONCLUSIONS
  Increased age, depressive features, and even minimal cognitive impairment, as determined clinically by Clinical Dementia Rating sum of boxes and by slowed psychomotor performance, identify older individuals without dementia who develop dementia. Older adults who do not develop dementia have stable cognitive performance. The absence of practice effects may denote the subset of older adults without dementia with histopathologic AD, which may reflect a preclinical stage of the illness.
authors.affiliation: Department of Neurology, Alzheimer's Disease Research Center, School of Medicine, Washington University, St Louis, MO 63108, USA. galvinj@neuro.wustl.edu
authors.forename: James E
authors.initials: JE
authors.lastname: Galvin
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Powlishta
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wilkins
authors.forename: Daniel W
authors.initials: DW
authors.lastname: McKeel
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Grant
authors.forename: Martha
authors.initials: M
authors.lastname: Storandt
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000150:complications* / Q000175:diagnosis; D001057:Apolipoproteins E; D001344:Autopsy / Q000379:methods; D003704:Dementia / Q000150:complications*; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory / Q000502:physiology*; D008609:Mental Status Schedule; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011594:Psychometrics; D011597:Psychomotor Performance; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D001057:Apolipoproteins E