Neuropathology of older persons without cognitive impairment from two community-based studies

Bennett, David A.; Schneider, Julie A.; Arvanitakis, Zoe; Kelly, Jeremiah F.; Aggarwal, Neelum T.; Shah, Raj C.; Wilson, Robert S.

doi:10.1212/01.wnl.0000219668.47116.e6

Cited by 1,089 publications

(988 citation statements)

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“…For instance, animals with enriched environments are protected against cognitive impairment 28, 30 . Additionally in clinical settings it is also observed that clinical manifestations may not correlate with the neuropathological burden on postmortem examination 6, 31-33 , implying that the cognitive reserve may serve as a buffer against the Alzheimer’s disease neuropathological burden. Since MCI is considered to be a prodromal state to Alzheimer’s disease, one can invoke the cognitive reserve theory to explain the inverse association between cognitive activities and the odds of having MCI.…”

Section: Discussionmentioning

confidence: 99%

Engaging in Cognitive Activities, Aging, and Mild Cognitive Impairment: A Population-Based Study

Geda¹,

Topazian²,

Lewis³

et al. 2011

Journal of Neuropsychiatry

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We investigated whether engaging in cognitive activities is associated with mild cognitive impairment (MCI) in a cross-sectional study derived from an ongoing population-based study of normal cognitive aging and MCI in Olmsted County, Minnesota. A random sample of 1321 non-demented study participants ages 70 to 89 (n = 1124 cognitively normal persons and n = 197 subjects with MCI) was interviewed about the frequency of cognitive activities carried out in late life (within one year of the date of interview). Computer activities [OR (95% CI) = 0.50 (0.36, 0.71); p < .0001)], craft activities such as knitting, quilting, etc. [0.66 (0.47, 0.93); p = 0.019)], playing games [0.65 (0.47, 0.90); p = 0.010)], and reading books [0.67 (0.49, 0.94); p = 0.019)] were associated with decreased odds of having MCI. Social activities such as traveling were marginally significant [0.71 (0.51, 1.00); p = 0.050)]. Even though the point estimates for reading magazines, playing music, artistic activities, and group activities were associated with reduced odds of having MCI, none reached statistical significance. We could not expect to observe any difference between the two groups on the variable of reading newspapers since almost identical proportions of the two groups (97.4% of normals and 97.5% of the MCI group) were engaged in reading newspapers on a regular basis.

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Section: Discussionmentioning

confidence: 99%

Engaging in Cognitive Activities, Aging, and Mild Cognitive Impairment: A Population-Based Study

Geda¹,

Topazian²,

Lewis³

et al. 2011

Journal of Neuropsychiatry

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“…The ''amyloid cascade'' hypothesis suggests that certain soluble or fibrillar A␤ species are critically involved in the early pathogenesis of AD (1), that fibrillar A␤ accumulation begins before cognitive decline (2), and that A␤-modifying treatments now in development may be most effective if initiated before significant A␤ neuropathology or symptoms become established (3). Postmortem neuropathological studies find significant fibrillar A␤ burden in many older people who were cognitively normal (2,4,5). Antemortem brain imaging studies are needed to determine the extent to which fibrillar A␤ in cognitively normal people predicts the subsequent development of clinical AD.…”

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confidence: 99%

Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease

Reiman

Chen

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

697

549

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Fibrillar amyloid-beta (A␤) is found in the brains of many cognitively normal older people. Whether or not this reflects a predisposition to Alzheimer's disease (AD) is unknown. We used Pittsburgh Compound B (PiB) PET to characterize the relationship between fibrillar A␤ burden and this predisposition in cognitively normal older people at 3 mean levels of genetic risk for AD. Dynamic PiB PET scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest (ROIs) were used to characterize and compare cerebral-to-cerebellar PIB distribution volume ratios, reflecting fibrillar A␤ burden, in 28 cognitively normal persons (mean age, 64 years) with a reported family history of AD and 2 copies, 1 copy, and no copies of the apolipoprotein E (APOE) 4 allele. The 8 4 homozygotes, 8 heterozygotes, and 12 noncarriers did not differ significantly in terms of age, sex, or cognitive scores. Fibrillar A␤ was significantly associated with APOE 4 carrier status and 4 gene dose in AD-affected mean cortical, frontal, temporal, posterior cingulate-precuneus, parietal, and basal ganglia ROIs, and was highest in an additional homozygote who had recently developed mild cognitive impairment. These findings suggest that fibrillar A␤ burden in cognitively normal older people is associated with APOE 4 gene dose, the major genetic risk factor for AD. Additional studies are needed to track fibrillar A␤ accumulation in persons with different kinds and levels of AD risk; to determine the extent to which fibrillar A␤, alone or in combination with other biomarkers and risk factors, predicts rates of cognitive decline and conversion to clinical AD; and to establish the role of fibrillar A␤ imaging in primary prevention trials.apolipoprotein E ͉ Pittsburgh Compound B PET

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“…1 Approximately 30% of cognitively normal subjects have intermediate-to high-likelihood AD pathology at autopsy. [2][3][4][5][6][7] According to this theory, subjects with greater cognitive reserve require a more severe neuropathologic burden to reach the threshold for clinical dementia. 8 Previous clinicopathologic studies suggest that although education is not directly related to the development of neuropathologic lesions, it appears to reduce the impact of such lesions on the development of dementia, thereby increasing cognitive reserve.…”

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confidence: 99%

Very low levels of education and cognitive reserve

Farfel

Nitrini²,

Suemoto³

et al. 2013

Neurology

Self Cite

145

112

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Objective: We conducted a clinicopathologic study in a large population with very low levels of education to determine whether very few years of education could contribute to cognitive reserve and modify the relation of neuropathologic indices to dementia. Methods:In this cross-sectional study, we included 675 individuals 50 years of age or older from the Brazilian Aging Brain Study Group. Cognitive abilities were evaluated through a structured interview with an informant at the time of autopsy, including the Clinical Dementia Rating (CDR) scale. Neuropathologic examinations were performed using immunohistochemistry and following internationally accepted criteria. Multivariate linear regression models were conducted to determine whether the association between cognitive abilities (measured by CDR sum of boxes) and years of education was independent of sociodemographic variables and neuropathologic indices, including neuritic plaques, neurofibrillary tangles, lacunar infarctions, small-vessel disease, and Lewy bodies. In addition, interaction models were used to examine whether education modified the relation between neuropathologic indices and cognition.Results: Mean education was 3.9 6 3.5 years. The cognitive reserve theory is increasingly used to explain the clinicopathologic dissociation observed in Alzheimer disease (AD). 1 Approximately 30% of cognitively normal subjects have intermediate-to high-likelihood AD pathology at autopsy. [2][3][4][5][6][7] According to this theory, subjects with greater cognitive reserve require a more severe neuropathologic burden to reach the threshold for clinical dementia. 8 Previous clinicopathologic studies suggest that although education is not directly related to the development of neuropathologic lesions, it appears to reduce the impact of such lesions on the development of dementia, thereby increasing cognitive reserve. However, the studies supporting this hypothesis have investigated populations with relatively high levels of educational attainment, with mean formal education ranging from 9 to 18 years. [8][9][10][11][12] Little information is available regarding the effect of very few years of education on cognitive reserve. Low educational attainment is the reality for a high proportion of the elderly worldwide. According to a report from the United Nations Education, Scientific and Cultural Organization, nearly 800 million adults remained illiterate in 2009, representing about 16% of the global population. 13 Most of

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Neuropathology of older persons without cognitive impairment from two community-based studies

Abstract: Alzheimer disease pathology can be found in the brains of older persons without dementia or mild cognitive impairment and is related to subtle changes in episodic memory.

Cited by 1,089 publications

References 57 publications

Engaging in Cognitive Activities, Aging, and Mild Cognitive Impairment: A Population-Based Study

Engaging in Cognitive Activities, Aging, and Mild Cognitive Impairment: A Population-Based Study

Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease

Very low levels of education and cognitive reserve

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