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

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 ϵ4 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. SD = standard deviation; SE = standard error.

[1]  J. Raven,et al.  Manual for Raven's progressive matrices and vocabulary scales , 1962 .

[2]  R. Kleemeier.  Intellectual change in the senium , 1962 .

[3]  S. Katz,et al.  STUDIES OF ILLNESS IN THE AGED. THE INDEX OF ADL: A STANDARDIZED MEASURE OF BIOLOGICAL AND PSYCHOSOCIAL FUNCTION. , 1963, JAMA.

[4]  Klaus F. Riegel,et al.  Development, Drop, and Death. , 1972 .

[5]  E. Palmore,et al.  Aging, terminal decline, and terminal drop. , 1976, Journal of gerontology.

[6]  Ruth B. Ekstrom,et al.  Manual for kit of factor-referenced cognitive tests , 1976 .

[7]  J. Botwinick,et al.  Predicting death from behavioral test performance. , 1978, Journal of gerontology.

[8]  L. Jarvik,et al.  "Critical loss" in the eighth and ninth decades. , 1981, Journal of gerontology.

[9]  J. Ware,et al.  Random-effects models for longitudinal data. , 1982, Biometrics.

[10]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[11]  B Johansson,et al.  The robustness of the terminal decline phenomenon: longitudinal data from the Digit-Span Memory Test. , 1989, Journal of gerontology.

[12]  A. Hofman,et al.  The association between change in cognitive function and longevity in Dutch elderly. , 1990, American journal of epidemiology.

[13]  R B Wallace,et al.  Longitudinal application of cognitive function measures in a defined population of community-dwelling elders. , 1991, Annals of epidemiology.

[14]  M. Albert,et al.  Use of brief cognitive tests to identify individuals in the community with clinically diagnosed Alzheimer's disease. , 1991, The International journal of neuroscience.

[15]  E. Sullivan,et al.  Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability. , 1991, Brain : a journal of neurology.

[16]  N. Butters,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part V. A normative study of the neuropsychological battery , 1994, Neurology.

[17]  P. Leaf,et al.  The effects of cognitive impairment on 9-year mortality in a community sample. , 1995, The journals of gerontology. Series B, Psychological sciences and social sciences.

[18]  J. Greene.  Contributions to Neuropsychological Assessment , 1995 .

[19]  L. Bäckman,et al.  Time to Death and Cognitive Performance , 1999 .

[20]  K. Schaie,et al.  Cognitive and sociodemographic risk factors for mortality in the Seattle Longitudinal Study. , 1999, The journals of gerontology. Series B, Psychological sciences and social sciences.

[21]  L. Berkman,et al.  Cognitive impairment and mortality in the community-dwelling elderly. , 2000, American journal of epidemiology.

[22]  C B Hall,et al.  A change point model for estimating the onset of cognitive decline in preclinical Alzheimer's disease. , 2000, Statistics in medicine.

[23]  T Ostbye,et al.  A reevaluation of the duration of survival after the onset of dementia. , 2001, The New England journal of medicine.

[24]  K. Anstey,et al.  Demographic, health, cognitive, and sensory variables as predictors of mortality in very old adults. , 2001, Psychology and aging.

[25]  L. Fratiglioni,et al.  Mortality-Related Differences and Changes in Episodic Memory Among the Oldest Old: Evidence From a Population-Based Sample of Nonagenarians , 2002 .

[26]  David A Bennett,et al.  The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period. , 2002, Archives of neurology.

[27]  D. A. Bennett,et al.  Natural history of mild cognitive impairment in older persons , 2002, Neurology.

[28]  G. Mcclearn,et al.  Terminal decline and markers of cerebro- and cardiovascular disease: findings from a longitudinal study of the oldest old. , 2002, The journals of gerontology. Series B, Psychological sciences and social sciences.

[29]  R. Brookmeyer,et al.  Survival following a diagnosis of Alzheimer disease. , 2002, Archives of neurology.

[30]  H. Bosworth,et al.  Terminal Change in Cognitive Function: An Updated Review of Longitudinal Studies , 2002, Experimental aging research.

[31]  J. Schneider,et al.  Individual differences in rates of change in cognitive abilities of older persons. , 2002, Psychology and aging.

[32]  Charles Hall,et al.  Modeling memory decline in older adults: the importance of preclinical dementia, attrition, and chronological age. , 2003, Psychology and aging.

[33]  D. Bennett,et al.  Terminal decline in cognitive function , 2003, Neurology.

[34]  Lisa Barnes,et al.  Assessment of Lifetime Participation in Cognitively Stimulating Activities , 2003, Journal of clinical and experimental neuropsychology.

[35]  L. Fratiglioni,et al.  Terminal decline and cognitive performance in very old age: does cause of death matter? , 2003, Psychology and aging.

[36]  E. Cochran,et al.  Apolipoprotein E ε4 allele, AD pathology, and the clinical expression of Alzheimer’s disease , 2003, Neurology.

[37]  Jason C. Allaire,et al.  Change in cognitive capabilities in the oldest old: the effects of proximity to death in genetically related individuals over a 6-year period. , 2004, Psychology and aging.

[38]  U. Lindenberger,et al.  Studying individual aging in an interindividual context: typical paths of age-related, dementia-related, and mortality-related cognitive development in old age. , 2005, Psychology and aging.

[39]  Parkinsonian signs in subjects with mild cognitive impairment. , 2005, Neurology.

[40]  B. Wilson.  The clinical neuropsychologist's dilemma , 2005, Journal of the International Neuropsychological Society.

[41]  D. Bennett,et al.  Early and late life cognitive activity and cognitive systems in old age , 2005, Journal of the International Neuropsychological Society.

[42]  David A. Bennett,et al.  The Rush Memory and Aging Project: Study Design and Baseline Characteristics of the Study Cohort , 2005, Neuroepidemiology.

[43]  D. Bennett,et al.  Amyloid mediates the association of apolipoprotein E e4 allele to cognitive function in older people , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[44]  D. Bennett,et al.  Odor Identification and Decline in Different Cognitive Domains in Old Age , 2006, Neuroepidemiology.

[45]  D. Bennett,et al.  Mild cognitive impairment , 2006, Neurology.