Relation of cerebral infarctions to dementia and cognitive function in older persons

Schneider, Julie A.; Wilson, Robert S.; Cochran, Elizabeth J.; Bienias, Julia L.; Arnold, Steven E.; Evans, Denis A.; Bennett, David A.

doi:10.1212/01.wnl.0000055863.87435.b2

Cited by 275 publications

(260 citation statements)

References 43 publications

Supporting

Mentioning

240

Contrasting

Unclassified

Order By: Relevance

“…A uniform gross and microscopic neuropathologic examination including postmortem indices of Alzheimer disease (AD) and Lewy body pathology was conducted as previously described. 18 Microvascular pathology. Microscopic cerebral infarcts.…”

Section: Postmortem Brain Assessmentmentioning

confidence: 99%

“…We reviewed 1-cm slabs and recorded the age, volume (in mm 3 ), side, and location of all cerebral infarcts visible to the naked eye as previously reported. 18 Hemorrhagic infarcts were included in analyses. There was no minimum size required for macroscopic infarcts.…”

Section: Postmortem Brain Assessmentmentioning

confidence: 99%

“…For quantity, we created a predictor with 3 levels: no (reference level), one, and multiple macroscopic infarcts, as previously described. 18 For location, we created 2 variables: cortical (presence of any microscopic infarcts in any cortical region; reference 5 no cortical microscopic infarcts) and subcortical microscopic infarcts (presence of any microscopic infarcts in any subcortical region; reference 5 no subcortical microscopic infarcts). To investigate quantity and location simultaneously, we created 4 variables: one and multiple cortical microscopic infarcts (compared to persons with no cortical macroscopic infarcts), and one and multiple subcortical microscopic infarcts (compared to no subcortical microscopic infarcts).…”

Section: Postmortem Brain Assessmentmentioning

confidence: 99%

See 2 more Smart Citations

Microvascular brain pathology and late-life motor impairment

Buchman

Boyle

et al. 2013

Neurology

View full text Add to dashboard Cite

Objective: To test the hypothesis that microvascular brain pathology is associated with late-life motor impairment.Methods: More than 2,500 persons participating in the Religious Orders Study or the Memory and Aging Project agreed to annual motor assessment and autopsy. Brains from 850 deceased participants were assessed for microvascular pathology including microinfarcts, cerebral amyloid angiopathy, and arteriolosclerosis, and we examined their association with global motor scores proximate to death.Results: Mean age at death was 88.5 years. More than 60% of cases had evidence of 1 or more microvascular pathologies and of these more than half did not have observed macroinfarcts. In separate regression models adjusted for age, sex, and education, microinfarcts and arteriolosclerosis were associated with level of motor function proximate to death (arteriolosclerosis, estimate, 20.027, SE 0.005, p , 0.001; microinfarcts, estimate, 20.017, SE 0.008, p 5 0.026). These associations were not attenuated when controlling for vascular risk factors and diseases, postmortem interval, or interval from last clinical examination, and did not vary with level of cognition or presence of dementia proximate to death. When the 3 microvascular pathologies, macroinfarcts, and atherosclerosis were considered together in a single model, more severe arteriolosclerosis (estimate, 20.021, SE 0.005, p , 0.001) and macroinfarcts (estimate, 20.019, SE 0.006, p , 0.001) showed separate effects with the level of motor function proximate to death. As our population ages, the increasing burden of chronic motor impairments and disability is a growing public health challenge. Impaired motor function is a common consequence of aging and is present in 50% of adults by age 85 years. Conclusions:1 Importantly, these impairments are progressive and associated with adverse health outcomes including mortality, falls, disability, and dementia, 2 but the pathologic basis for these impairments is unclear. Vascular disease is common with increasing age. Converging evidence suggests that small-vessel disease may be a systemic agerelated disorder which affects many organs including heart, kidney, and retina. [3][4][5][6] Similarly, even in the absence of stroke, brain imaging of older adults shows that lacunar infarcts as well as nonspecific white matter hyperintensities commonly thought of as surrogates for microvascular brain pathology are common in old age and associated with impaired cognition, gait, balance, falls, motor speed, and disability. [7][8][9][10][11][12] While conventional brain imaging is an excellent tool for identifying many types of vascular pathologies, it cannot identify specific small-vessel diseases and the extent to which these pathologies are related to late-life motor impairments. 7,[13][14][15] To address these gaps in the literature, we used clinical and postmortem data from the first 850 decedents in the From the Rush Alzheimer's Disease Center (A

show abstract

Section: Postmortem Brain Assessmentmentioning

confidence: 99%

Section: Postmortem Brain Assessmentmentioning

confidence: 99%

Section: Postmortem Brain Assessmentmentioning

confidence: 99%

See 1 more Smart Citation

Microvascular brain pathology and late-life motor impairment

Buchman

Boyle

et al. 2013

Neurology

View full text Add to dashboard Cite

show abstract

“…Slabs from one cerebral hemisphere and one cerebellar hemisphere and all slabs with suspected infarcts were fixed for at least 3 days in 4% paraformaldehyde. Suspected infarcts were processed for histologic confirmation 20,21 and the age (acute, subacute, chronic) was noted. One hemisphere was examined for microinfarcts in 6 cortical regions, 2 subcortical regions, and the midbrain using 6-mm paraffin-embedded sections stained with hematoxylin & eosin.…”

Section: 14mentioning

confidence: 99%

P3–192: Life‐span cognitive activity, neuropathologic burden and cognitive aging

James

Wilson

Boyle

et al. 2013

Alzheimer's & Dementia

View full text Add to dashboard Cite

Objective: To test the hypothesis that cognitive activity across the life span is related to late-life cognitive decline not linked to common neuropathologic disorders.Methods: On enrollment, older participants in a longitudinal clinical-pathologic cohort study rated late-life (i.e., current) and early-life participation in cognitively stimulating activities. After a mean of 5.8 years of annual cognitive function testing, 294 individuals had died and undergone neuropathologic examination. Chronic gross infarcts, chronic microscopic infarcts, and neocortical Lewy bodies were identified, and measures of b-amyloid burden and tau-positive tangle density in multiple brain regions were derived.Results: In a mixed-effects model adjusted for age at death, sex, education, gross and microscopic infarction, neocortical Lewy bodies, amyloid burden, and tangle density, more frequent late-life cognitive activity (estimate 5 0.028, standard error [SE] 5 0.008, p , 0.001) and early-life cognitive activity (estimate 5 0.034, SE 5 0.013, p 5 0.008) were each associated with slower cognitive decline. The 2 measures together accounted for 14% of the residual variability in cognitive decline not related to neuropathologic burden. The early-life-activity association was attributable to cognitive activity in childhood (estimate 5 0.027, SE 5 0.012, p 5 0.026) and middle age (estimate 5 0.029, SE 5 0.013, p 5 0.025) but not young adulthood (estimate 5 20.020, SE 5 0.014, p 5 0.163).Conclusions: More frequent cognitive activity across the life span has an association with slower late-life cognitive decline that is independent of common neuropathologic conditions, consistent with the cognitive reserve hypothesis. Participation in cognitively stimulating activities has been associated with reduced late-life cognitive decline in most [1][2][3][4][5] although not all 6 studies, but the mechanisms underlying the association are not well understood. One idea is that cognitive activity somehow helps delay the cognitive consequences of neuropathologic lesions (cognitive reserve hypothesis 7-9 ), possibly because of activity-dependent changes in key cognitive systems in the brain.10,11 Alternatively, cognitive inactivity may be a consequence of neuropathologic lesions rather than a risk factor (reverse causality hypothesis 1,2,12 ). Establishing the direction of the association between change in cognitive activity and cognitive function over time could differentiate the hypotheses, but this has been difficult to do in observational studies. 1,2,6,13 Determining whether the association between cognitive activity and cognitive decline is attributable to (reverse causality hypothesis) or independent of (cognitive reserve hypothesis) neuropathologic conditions could also differentiate the hypotheses, but little relevant data have been published. 5 We used data from participants in the Rush Memory and Aging Project to test the hypothesis that cognitive activity has an association with cognitive decline that is independent of common neuropatho...

show abstract

“…Cerebral infarction is common. Thus, in the Religious Orders Study , a longitudinal clinical-pathologic study of Catholic clergy members with a mean age at death of about 85, more than one third had one or more chronic cerebral infarctions on brain autopsy (Schneider, Wilson, Bienias, Evans, & Bennett, 2004;Schneider et al, 2003). Both infarction and Alzheimer's disease pathology were negatively associated with level of cognitive function proximate to death, and these associations were independent, meaning the negative effects were additive.…”

Section: Age-related Neuropathologymentioning

confidence: 99%

Neurological Factors in Cognitive Aging

Wilson¹

2008

Handbook of Cognitive Aging: Interdisciplinary Perspectives

View full text Add to dashboard Cite

Relation of cerebral infarctions to dementia and cognitive function in older persons

Cited by 275 publications

References 43 publications

Microvascular brain pathology and late-life motor impairment

Microvascular brain pathology and late-life motor impairment

P3–192: Life‐span cognitive activity, neuropathologic burden and cognitive aging

Neurological Factors in Cognitive Aging

Contact Info

Product

Resources

About