4.3 Article

The Natural History of Cognitive Decline in Alzheimer's Disease

Journal

PSYCHOLOGY AND AGING
Volume 27, Issue 4, Pages 1008-1017

Publisher

AMER PSYCHOLOGICAL ASSOC
DOI: 10.1037/a0029857

Keywords

longitudinal study; cognitive decline; Alzheimer's disease; mild cognitive impairment; neuropathologic examination

Funding

  1. NIA NIH HHS [R01AG17917, R01 AG017917, R01 AG015819, R01AG33678, R01AG34374, R01 AG033678, R01 AG034374, P30 AG010161, R01AG15819, P30AG10161] Funding Source: Medline

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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.

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