Neurodegenerative basis of age-related cognitive decline

Abstract

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.

Speech Recognition in Adults With Cochlear Implants: The Effects of Working Memory, Phonological Sensitivity, and Aging

“…Age-related declines in general cognition have been well recognized (Hällgren, Larsby, Lyxell, & Arlinger, 2001;Humes, 2005;Van Rooij & Plomp, 1990;Wilson, Leurgans, Boyle, Schneider, & Bennett, 2010). One cognitive function that is particularly relevant to success in speech recognition for individuals with hearing loss, and has been used to document evidence of age-related declines, is verbal working memory (WM; e.g., Bopp & Verhaeghen, 2005;Kumar & Priyadarshi, 2014;Nittrouer, Lowenstein, Wucinich, & Moberly, 2016;Rönnberg et al, 2013).…”

TOMM40 ′523 variant and cognitive decline in older persons with APOE ε3/3 genotype

“…22 We reported previously that APOE e4 was associated with both preterminal and terminal decline. 23 Therefore, we explored the influence of the 9523 variant on terminal decline by using random change point models, a common modeling approach for nonlinear change.…”

Terminal decline and practice effects in older adults without dementia

“…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.…”

“…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.…”

“…9,10 Although the endpoint in our analysis is death, rather than the incidence of MCI or dementia, the biological aging process leading to death could be accompanied by a similar pathologic burden as that in dementing diseases, suppressing practice effects at their earliest stage. In fact, in the Religious Orders Study, 4 age-related decline in cognitive function was mainly attributable to the same neurodegenerative pathology traditionally associated with dementia. Neurofibrillary tangles, cerebral infarction, and neocortical Lewy bodies all contributed to gradual age-related cognitive decline, while little age-related decline was observed in the absence of these lesions.…”