Onset of terminal decline in cognitive abilities in individuals without dementia

Thorvaldsson, Valgeir; Hofer, Scott M.; Berg, Stig; Skoog, I.; Sacuiu, Simona; Johansson, Boo

doi:10.1212/01.wnl.0000312379.02302.ba

Cited by 79 publications

(92 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The first analytic goal was to partition cognitive paths into slow change and rapid change components. Previous research in this 10 and other 11,12,19 cohorts indicates that cognitive decline tends to markedly accelerate in the last few years of life. To identify this point, we constructed a series of mixed-effect models 20 that allowed rate of cognitive decline to change in the last n months before death.…”

Section: Assessment Of Cognitive Functionmentioning

confidence: 68%

Neurodegenerative basis of age-related cognitive decline

et al. 2010

View full text Add to dashboard Cite

Objective: To assess the contribution of dementia-related neuropathologic lesions to age-related and disease-related change in cognitive function. Methods:A total of 354 Catholic nuns, priests, and brothers had annual clinical evaluations for up to 13 years, died, and underwent brain autopsy. The clinical evaluations included detailed testing of cognitive function from which previously established composite measures of global cognition and specific cognitive functions were derived. As part of a uniform neuropathologic evaluation, the density of neurofibrillary tangles was summarized in a composite measure and the presence of Lewy bodies and gross and microscopic cerebral infarction was noted.Results: During follow-up, rate of global cognitive decline was gradual at first and then more than quadrupled in the last 4 to 5 years of life consistent with the onset of progressive dementia. Neurofibrillary tangles, cerebral infarction, and neocortical Lewy bodies all contributed to gradual age-related cognitive decline and little age-related decline was evident in the absence of these lesions. Neurofibrillary tangles and neocortical Lewy bodies contributed to precipitous diseaserelated cognitive decline, but substantial disease-related decline was evident even in the absence of these lesions. Conclusion:Mild age-related decline in cognitive function is mainly due to the neuropathologic lesions traditionally associated with dementia. Neurology Much cognitive loss in old age is limited to very subtle decline evolving slowly over a period of years. The neurobiologic mechanisms underlying these changes are not known. Traditionally, this gradual age-related decline has been attributed to normative developmental processes and distinguished from the precipitous cognitive decline attributed to pathologic processes such as those underlying Alzheimer disease (AD) and other common dementias. However, few clinical-pathologic studies have examined the relation of pathologic indices to change in cognitive function over time, 1,2 and none of these has separated slowly progressive age-related change from more rapid disease-related decline. Thus, knowledge about the contribution of common neurodegenerative lesions to cognitive aging is limited.In the present study, we test the hypothesis that the neurodegenerative lesions associated with late-life dementia, including AD pathology, cerebrovascular disease, and Lewy bodies, contribute to age-related cognitive decline. The hypothesis is based on the observations that these neuropathologic lesions are commonly observed in the brains of old people who die with no or mild cognitive impairment 3-8 and their cross-sectional correlation with level of cognitive function in persons without dementia is comparable to the correlation seen in persons with e-Pub ahead of print on September 15, 2010, at www.neurology.org.

show abstract

Section: Assessment Of Cognitive Functionmentioning

confidence: 68%

Neurodegenerative basis of age-related cognitive decline

et al. 2010

View full text Add to dashboard Cite

show abstract

“…This is suggested by the terminal cognitve decline observed in the elderly without dementia years before death. [33][34][35] Alternatively, AD pathology in cognitive regions might serve as a proxy for AD pathology in other brain regions that regulate components of frailty (e.g., primary motor cortex). Last, frailty and AD pathology may share an underlying etiopathogenesis (e.g., vascular pathology, energy production, stress).…”

Section: Discussionmentioning

confidence: 99%

Physical frailty in older persons is associated with Alzheimer disease pathology

Buchman

Schneider²,

Leurgans³

et al. 2008

Neurology

215

181

View full text Add to dashboard Cite

Objective: We examined the extent to which physical frailty in older persons is associated with common age-related brain pathology, including cerebral infarcts, Lewy body pathology, and Alzheimer disease (AD) pathology. Methods:We studied brain autopsies from 165 deceased participants from the Rush Memory and Aging Project, a longitudinal clinical-pathologic study of aging. Physical frailty, based on four components, including grip strength, time to walk 8 feet, body composition, and fatigue, was assessed at annual clinical evaluations. Multiple regression analyses were used to examine the relation of postmortem neuropathologic findings to frailty proximate to death, controlling for age, sex, and education. Results:The mean age at death was 88.1 years (SD ϭ 5.7 years). The level of AD pathology was associated with frailty proximate to death (␤ ϭ 0.252, SE ϭ 0.077, p ϭ 0.001), accounting for 4% of the variance of physical frailty. Neither cerebral infarcts (␤ ϭ Ϫ0.121, SE ϭ 0.115, p ϭ 0.294) nor Lewy body disease pathology (␤ ϭ 0.07, SE ϭ 0.156, p ϭ 0.678) was associated with frailty. These associations were unchanged after controlling for the time interval from last clinical evaluation to autopsy. The association of AD pathology with frailty did not differ by the presence of dementia, and this association was unchanged even after considering potential confounders, including physical activity; parkinsonian signs; pulmonary function; or history of chronic diseases, including vascular risk factors, vascular disease burden, falls, joint pain, or use of antipsychotic or antihypertensive medications. Physical frailty is common in the elderly and associated with adverse health outcomes, but its underlying biology is poorly understood. Although frailty is a heterogeneous syndrome, a number of features, including strength, gait, body composition, and fatigue, are generally accepted as core components of physical frailty. Conclusion:1,2 Cerebral infarcts and Lewy body disease are known to be associated with impaired physical performance.3,4 Furthermore, recent work by several groups suggests that several core components of frailty, including impaired grip strength, slowed gait, and low body mass index (BMI), predict subsequent development of dementia.5-7 These reports suggest that common brain pathology may contribute to physical frailty in the elderly.We used data from the Rush Memory and Aging Project, 8 a longitudinal epidemiologic clinical-pathologic study of chronic conditions of aging, to examine to what extent common

show abstract

“…While previous studies have confirmed the existence of terminal decline, [3][4][5][6][7] they have inadequately addressed practice or learning effects in cognitive test performance. Practice effects refer to the improvement in cognitive test scores over repeated administrations of cognitive tests.…”

mentioning

confidence: 97%

“…However, even in the absence of clinically diagnosed dementia, and after accounting for other illnesses, declining cognitive function is also associated with mortality. [1][2][3][4][5][6][7] Therefore, cognitive decline could reflect biological aging independently of dementia. The concept of terminal cognitive decline refers to the relatively precipitous drop in cognitive function occurring in the years preceding death.…”

mentioning

confidence: 99%

Terminal decline and practice effects in older adults without dementia

et al. 2011

View full text Add to dashboard Cite

Objective: To track cognitive change over time in dementia-free older adults and to examine terminal cognitive decline.Methods: A total of 1,230 subjects who remained free from dementia over 14 years of follow-up were included in a population-based epidemiologic cohort study. First, we compared survivors and decedents on their trajectories of 5 cognitive functions (learning, memory, language, psychomotor speed, executive functions), dissociating practice effects which can mask clinically significant decline from age-associated cognitive decline. We used longitudinal mixed-effects models with penalized linear spline. Second, limiting the sample to 613 subjects who died during follow-up, we identified the inflection points at which the rate of cognitive decline accelerated, in relation to time of death, controlling for practice effects. We used mixed-effects model with a change point.Results: Age-associated cognitive trajectories were similar between decedents and survivors without dementia. However, substantial differences were observed between the trajectories of practice effects of survivors and decedents, resembling those usually observed between normal and mildly cognitively impaired elderly. Executive and language functions showed the earliest terminal declines, more than 9 years prior to death, independent of practice effects.

show abstract

Onset of terminal decline in cognitive abilities in individuals without dementia

Abstract: There is substantial acceleration in cognitive decline many years prior to death among individuals without dementia. Time of onset and rate of terminal decline vary considerably across cognitive abilities.

Cited by 79 publications

References 16 publications

Neurodegenerative basis of age-related cognitive decline

Neurodegenerative basis of age-related cognitive decline

Physical frailty in older persons is associated with Alzheimer disease pathology

Terminal decline and practice effects in older adults without dementia

Contact Info

Product

Resources

About