Mild cognitive impairment

Boyle, P. A.; Wilson, Robert S.; Aggarwal, Neelum T.; Tang, Yuxiao; Bennett, David A.

doi:10.1212/01.wnl.0000228244.10416.20

Cited by 268 publications

(258 citation statements)

References 36 publications

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“…Interestingly, a recent study that screened for gene-expression profiles associated with mild cognitive impairment (MCI), a clinical transitional stage between aging and AD dementia (44), found that among the genes that showed a strong negative correlation with cognitive performance were those encoding the glutamate receptors GluA3 and GluN2B (45). It is tempting to speculate that people with relatively low levels of GluA3 and GluN2B expression are less likely to develop MCI despite the presence of Aβ oligomers.…”

Section: Discussionmentioning

confidence: 99%

Amyloid-β effects on synapses and memory require AMPA receptor subunit GluA3

Reinders

Pao

Renner

et al. 2016

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

107

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Amyloid-β (Aβ) is a prime suspect for causing cognitive deficits during the early phases of Alzheimer’s disease (AD). Experiments in AD mouse models have shown that soluble oligomeric clusters of Aβ degrade synapses and impair memory formation. We show that all Aβ-driven effects measured in these mice depend on AMPA receptor (AMPAR) subunit GluA3. Hippocampal neurons that lack GluA3 were resistant against Aβ-mediated synaptic depression and spine loss. In addition, Aβ oligomers blocked long-term synaptic potentiation only in neurons that expressed GluA3. Furthermore, although Aβ-overproducing mice showed significant memory impairment, memories in GluA3-deficient congenics remained unaffected. These experiments indicate that the presence of GluA3-containing AMPARs is critical for Aβ-mediated synaptic and cognitive deficits.

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Section: Discussionmentioning

confidence: 99%

Amyloid-β effects on synapses and memory require AMPA receptor subunit GluA3

Reinders

Pao

Renner

et al. 2016

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

107

View full text Add to dashboard Cite

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“…[10][11][12][13][14][15][16][17] Briefly, the Memory and Aging Project (MAP) and Religious Orders Study (ROS) are ongoing clinical-pathologic epidemiologic studies of aging and dementia in older persons. Persons 65 years and older without known dementia…”

Section: Discussionmentioning

confidence: 99%

Estimating cerebral microinfarct burden from autopsy samples

et al. 2013

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Objective: To estimate whole-brain microinfarct burden from microinfarct counts in routine postmortem examination.Methods: We developed a simple mathematical method to estimate the total number of cerebral microinfarcts from counts obtained in the small amount of tissue routinely examined in brain autopsies. We derived estimates of total microinfarct burden from autopsy brain specimens from 648 older participants in 2 community-based clinical-pathologic cohort studies of aging and dementia.Results: Our results indicate that observing 1 or 2 microinfarcts in 9 routine neuropathologic specimens implies a maximum-likelihood estimate of 552 or 1,104 microinfarcts throughout the brain. Similar estimates were obtained when validating in larger sampled brain volumes. Conclusions:The substantial whole-brain burden of cerebral microinfarcts suggested by even a few microinfarcts on routine pathologic sampling suggests a potential mechanism by which these lesions could cause neurologic dysfunction in individuals with small-vessel disease. The estimation framework developed here may generalize to clinicopathologic correlations of other imaging-negative micropathologies. Neurology Cerebral microinfarcts are defined as ischemic infarctions, located anywhere in the brain, identifiable by microscopic but not visual inspection.1-3 In practice, these "invisible" lesions are typically less than 1-2 mm in diameter, and therefore smaller than the 3-15 mm diameters characteristic of lacunar infarcts.4,5 As a result, microinfarcts cannot be seen by either conventional structural neuroimaging or gross evaluation of brain slices. They are instead most commonly detected by microscopic examination of routinely selected brain sections, 2,6 or possibly as small acute infarcts on diffusion-weighted imaging (DWI) MRI. 7,8 Despite their small size, microinfarcts appear to be associated with dementia even after controlling for other neuropathologies (including macroscopic infarcts), 2,6 suggesting that microinfarct burden may be an important link between small-vessel disease and cognitive impairment.A crucial step in assessing the mechanism by which microinfarcts impact neurologic function is to determine their total burden in the brain. Microscopic sampling of the entire brain is not feasible, however. As a step toward overcoming this limitation, we present a simple method for estimating the total number of microinfarcts in the brain based on lesion counts obtained from routinely selected autopsy sections. Our findings suggest that the presence of even 1 or 2 microinfarcts in limited samples of brain tissue indicates a likely overall burden of hundreds of these small lesions.METHODS Data for this study were obtained from brain samples of 648 deceased and autopsied participants of the Rush Religious Orders Study and Memory and Aging project, 2 community-based clinical-pathologic cohort studies of aging and dementia (mean age at death 5 88.3 years, SD 5 6.6; 222 men, 426 women).9 Details of recruitment, clinical evaluation, cognitive tes...

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“…Annual follow‐up clinical evaluations are identical in all essential details and conducted by clinicians blinded to prior data. Cognitive function is evaluated at each evaluation using a standardized battery of 17 cognitive performance tests 19, 20. These include measures of episodic memory (i.e., word list memory, recall, and recognition, immediate and delayed recall of the East Boston story, and story A from Logical Memory), semantic memory (i.e., verbal fluency, a 15‐item form of the Boston Naming Test, and a modified NAART), working memory (i.e., digit span forward, digit span backward, and digit ordering), perceptual speed (i.e., number comparison and Symbol Digit Modalities Test), and visuospatial ability (i.e., short forms of Judgment of Line Orientation and Standard Progressive Matrices).…”

Section: Methodsmentioning

confidence: 99%

“…The clinical diagnosis of dementia follows accepted and validated criteria and diagnoses are made by clinicians with expertise in the evaluation of older persons following review of all clinical data. Diagnoses of MCI are rendered for persons judged to have cognitive impairment but not determined to have dementia, as detailed in numerous prior publications 17, 18, 20…”

Section: Methodsmentioning

confidence: 99%

White matter hyperintensities, incident mild cognitive impairment, and cognitive decline in old age

Boyle

Fleischman

et al. 2016

Ann Clin Transl Neurol

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ObjectiveExamine the association of white matter hyperintensities (WMH) with risk of incident mild cognitive impairment (MCI) and rate of decline in multiple cognitive systems in community‐based older persons.MethodsParticipants (n = 354) were older persons initially free of cognitive impairment from two ongoing longitudinal epidemiologic studies of aging. All underwent brain magnetic resonance imaging (MRI) for quantification of WMH and gray matter volumes and detailed annual clinical evaluations including 17 cognitive tests. Proportional hazards models were used to examine the relationship between WMH and incident MCI, and mixed‐effects models were used to examine the relationship between WMH and decline in global cognition and five specific cognitive systems.ResultsDuring up to about 6 years of follow‐up (mean = 4.1), 106 (30% of 354) persons developed MCI. In a proportional hazards model adjusted for age, gender, and education, WMH volume was associated with a substantially increased risk of MCI (P < 0.001). Thus, a person with a high WMH volume (90th percentile) was about 2.7 times more likely to develop MCI compared to a person with a low volume (10th percentile). WMH volume also was associated with an increased rate of decline in global cognition (P < 0.001), perceptual speed, working memory, episodic memory, and semantic memory. Associations persisted after adjustment for total gray matter volume, vascular risk factors, and vascular diseases.Interpretation WMH contribute to the development of MCI and are associated with progressive decline in multiple cognitive systems in old age.

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Mild cognitive impairment

Abstract: Mild cognitive impairment is associated with a greatly increased risk of incident Alzheimer disease and a more rapid rate of decline in cognitive function.

Cited by 268 publications

References 36 publications

Amyloid-β effects on synapses and memory require AMPA receptor subunit GluA3

Amyloid-β effects on synapses and memory require AMPA receptor subunit GluA3

Estimating cerebral microinfarct burden from autopsy samples

White matter hyperintensities, incident mild cognitive impairment, and cognitive decline in old age

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