Predictors of preclinical Alzheimer disease and dementia: a clinicopathologic study

Arch Neurol. 2005 May;62(5):758-65. doi: 10.1001/archneur.62.5.758.


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.

Design: Longitudinal study of memory and aging.

Setting: Alzheimer's Disease Research Center, St Louis, Mo.

Main outcome measures: Clinical Dementia Rating, its sum of boxes, and neuropathologic diagnosis of dementia.

Participants: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging*
  • Alzheimer Disease / complications*
  • Alzheimer Disease / diagnosis
  • Apolipoproteins E
  • Autopsy / methods
  • Dementia / complications*
  • Female
  • Geriatric Assessment
  • Humans
  • Longitudinal Studies
  • Male
  • Memory / physiology*
  • Mental Status Schedule
  • Neurologic Examination
  • Neuropsychological Tests
  • Predictive Value of Tests
  • Psychometrics
  • Psychomotor Performance
  • Severity of Illness Index
  • Statistics, Nonparametric


  • Apolipoproteins E