Neurodegenerative basis of age-related cognitive decline (e–Pub ahead of print)(CME)

Rush Alzheimer's Disease Center, Rush University Medical Center, 600 South Paulina Ave., Suite 1038, Chicago, IL 60612, USA.
Neurology (Impact Factor: 8.3). 09/2010; 75(12):1070-8. DOI: 10.1212/WNL.0b013e3181f39adc
Source: PubMed

ABSTRACT To assess the contribution of dementia-related neuropathologic lesions to age-related and disease-related change in cognitive function.
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.
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 disease-related cognitive decline, but substantial disease-related decline was evident even in the absence of these lesions.
Mild age-related decline in cognitive function is mainly due to the neuropathologic lesions traditionally associated with dementia.

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Available from: Patricia A Boyle, Apr 02, 2014
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    • "To provide a summary score of all tests in the cognitive battery, a global cognitive score was created using all 4 tests described above by averaging the z scores of each test. This method has been shown to minimize problems caused by measurement error on the individual tests.26 However, it does not reflect all aspects of cognition because it is limited by the content of the cognitive test battery. "
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    Neurology 01/2014; 82(4). DOI:10.1212/WNL.0000000000000063 · 8.30 Impact Factor
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    • "There have been several previous studies of factors reported to be associated with cognitive decline in AD patients that have not examined genetic factors. One suggests that the pathological findings such as neurofibrillary tangles, cerebral infarction, and Lewy bodies that mediate normal and pathological age-related cognitive decline also mediate more rapid cognitive decline in some AD patients [6]. Other reports have postulated superimposed medical factors to be associated with rate of decline in AD, including diabetes [7] and other vascular risk factors [8], kidney function [9], and muscle strength [10]. "
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    • "All clinical data collection and clinical classification were done without knowledge of previously collected data. Further information on this clinical classification system (Bennett, Schneider, Buchman, et al. 2005; Bennett, Schneider, Aggarwal, et al. 2006) and supporting neuropathological (Bennett, Schneider, Bienias, et al. 2005; Bennett, Schneider, Arvanitakis, et al. 2006) and clinical (Wilson, Krueger, et al., 2010; Boyle et al. 2006) data are published elsewhere. As part of each annual clinical evaluation, a modified version (Bennett et al. 1997) of the motor portion of the Unified Parkinson's Disease Rating Scale (Fahn and Elton 1987) was administered. "
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