The natural history of cognitive decline in Alzheimer's disease

Robert S. Wilson*, Eisuke Segawa, Patricia A. Boyle, Sophia E. Anagnos, Loren P. Hizel, David A. Bennett

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

191 Scopus citations


The study aim was to describe the temporal course of cognitive decline in Alzheimer's disease (AD). We selected 226 persons from 2 longitudinal clinical-pathological studies who were cognitively healthy at baseline, followed at least 4 years (M = 10.2, SD = 3.5), and clinically diagnosed with AD at some point during follow-up. Each evaluation included a battery of 17 cognitive tests from which a previously established composite measure of global cognition was derived. In those who died, a uniform neuropathologic examination established the pathological diagnoses of Alzheimer's disease and other common conditions that impair cognition. Mixed-effects models with 2 change points were used to assess trajectories of cognitive decline. In the main analysis, there was no change in cognitive function until a mean of 7.5 years before dementia was diagnosed (95% confidence interval [CI]: -8.3, -6.7). The global cognitive measure declined a mean of 0.087-unit per year (95% CI: -0.099, -0.073) until a mean of 2.0 years before the diagnosis (95% CI: -2.2, -1.7) when it increased more than 4-fold to a mean loss of 0.370-unit per year (95% CI: -0.417, -0.334). Of 126 individuals who died and underwent autopsy, 101 (80%) met pathologic criteria for AD, of whom 67 had at least one other pathologic condition. Pathologic measures of AD and cerebral infarction were not strongly related to cognitive trajectories. The results indicate that cognitive decline in AD begins many years before dementia is diagnosed and accelerates during the course of the disease.

Original languageEnglish (US)
Pages (from-to)1008-1017
Number of pages10
JournalPsychology and Aging
Issue number4
StatePublished - Dec 2012
Externally publishedYes


  • Alzheimer's disease
  • Cognitive decline
  • Longitudinal study
  • Mild cognitive impairment
  • Neuropathologic examination

ASJC Scopus subject areas

  • Social Psychology
  • Aging
  • Geriatrics and Gerontology


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