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Terminal Cognitive Decline: Accelerated Loss of Cognition in the Last Years of Life

From the Rush Alzheimer’s Disease Center (R.S.W., D.A.B.) and Rush Institute for Healthy Aging (T.L.B., J.L.B.) and the Departments of Neurological Sciences (R.S.W., D.A.B.), Behavioral Sciences (R.S.W.), and Internal Medicine (J.L.B.), Rush University Medical Center, Chicago, IL.

Address correspondence and reprint requests to Robert S. Wilson, Rush Alzheimer’s Disease Center, Rush University Medical Center, Suite 1038, Chicago, IL 60612. E-mail: rwilson{at}rush.edu

Objective: To test the hypothesis that rate of cognitive decline accelerates in the last years of life.

Methods: Participants are 853 older persons without dementia at study onset. For up to 8 years, they underwent annual clinical evaluations that included a battery of 19 cognitive tests from which previously established composite measures of global cognition and specific cognitive domains were derived. In analyses, we used linear mixed-effects models that allowed rate of cognitive decline to change at a given point before death to estimate the onset of a terminal decline period and rate of cognitive decline before and after that point. In subsequent analyses, we tested potential modifiers of terminal decline.

Results: There were 115 deaths. Those who died did not differ from survivors in their level of global cognitive function at study onset, but beginning a mean of 42 months before death, their rate of global cognitive decline sharply increased. The duration and rapidity of terminal decline in global cognition differed from person to person. Terminal cognitive decline was not modified by age, sex, education, or the presence of mild cognitive impairment, but it was not present in those with vascular disease (e.g., stroke and heart attack) or in those without at least one copy of the apolipoprotein E 4 allele, suggesting that Alzheimer’s disease pathology may contribute to the phenomenon.

Conclusions: In old age, cognitive decline markedly accelerates during the last 3 to 4 years of life, consistent with the terminal decline hypothesis.

Key Words: mortality • longitudinal studies • cognitive function • terminal decline • apolipoprotein E

Abbreviations: SD = standard deviation; SE = standard error.

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