Brain arteriolosclerosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Blevins BL
PROVIDER: S-EPMC8503820 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Although several forms of sleep disruption are associated with stroke, few studies have examined the relationship between sleep and histopathologic measures of cerebrovascular disease. We tested the hypothesis that greater sleep fragmentation is associated with a higher burden of cerebral vessel and infarct pathology at autopsy.We used ordinal logistic regression models to relate sleep fragmentation measured by actigraphy to the severity of arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy, and the number of macroscopic and microscopic infarcts assessed by structured brain autopsy in 315 participants from the Rush Memory and Aging Project.Greater sleep fragmentation was associated with more severe arteriolosclerosis (odds ratio, 1.27; 95% confidence interval, 1.02-1.59; P=0.03 per 1 SD greater sleep fragmentation) and more subcortical macroscopic infarcts (odds ratio, 1.31; 95% confidence interval, 1.01-1.68; P=0.04). These associations were independent of established cardiovascular risk factors and diseases, and several medical comorbidities.Sleep fragmentation is associated with arteriolosclerosis and subcortical infarcts in older adults.
| S-EPMC4780848 | biostudies-literature
Project description:Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.
| S-EPMC3891448 | biostudies-literature
Project description:Brain arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor function and higher odds of dementia. In spite of its frequency and associated morbidity, arteriolosclerosis can only be diagnosed at autopsy. Therefore, the purpose of this work was to develop an in-vivo classifier of arteriolosclerosis based on brain MRI. First, an ex-vivo classifier of arteriolosclerosis was developed based on features related to white matter hyperintensities, diffusion anisotropy and demographics by applying machine learning to ex-vivo MRI and pathology data from 119 participants of the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS), two longitudinal cohort studies of aging that recruit non-demented older adults. The ex-vivo classifier showed good performance in predicting the presence of arteriolosclerosis, with an average area under the receiver operating characteristic curve AUC = 0.78. The ex-vivo classifier was then translated to in-vivo based on available in-vivo and ex-vivo MRI data on the same participants. The in-vivo classifier was named ARTS (short for ARTerioloSclerosis), is fully automated, and provides a score linked to the likelihood a person suffers from arteriolosclerosis. The performance of ARTS in predicting the presence of arteriolosclerosis in-vivo was tested in a separate, 91% dementia-free group of 79 MAP/ROS participants and exhibited an AUC = 0.79 in persons with antemortem intervals shorter than 2.4 years. This level of performance in mostly non-demented older adults is notable considering that arteriolosclerosis can only be diagnosed at autopsy. The scan-rescan reproducibility of the ARTS score was excellent, with an intraclass correlation of 0.99, suggesting that application of ARTS in longitudinal studies may show high sensitivity in detecting small changes. Finally, higher ARTS scores in non-demented older adults were associated with greater decline in cognition two years after baseline MRI, especially in perceptual speed which has been linked to arteriolosclerosis and small vessel disease. This finding was shown in a separate group of 369 non-demented MAP/ROS participants and was validated in 72 non-demented Black participants of the Minority Aging Research Study (MARS) and also in 244 non-demented participants of the Alzheimer's Disease Neuroimaging Initiative 2 and 3. The results of this work suggest that ARTS may have broad implications in the advancement of diagnosis, prevention and treatment of arteriolosclerosis. ARTS is publicly available at https://www.nitrc.org/projects/arts/.
| S-EPMC8329541 | biostudies-literature
Project description:Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative data sets. Previous studies showed evidence of distinct neurodegenerative disease outcomes and clinical-pathological correlations in the "oldest-old" compared to younger cohorts. Therefore, using the National Alzheimer's Coordinating Center data set, we analyzed clinical and neuropathological data from two groups according to ages at death: < 80 years (n = 1008) and ≥80 years (n = 1382). In both age groups, severe brain arteriolosclerosis was associated with worse performances on global cognition tests. Hypertension (but not diabetes) was a brain arteriolosclerosis risk factor in the younger group. In the ≥ 80 years age at death group, an ABCC9 gene variant (rs704180), previously associated with aging-related hippocampal sclerosis, was also associated with brain arteriolosclerosis. A post-hoc arterial spin labeling neuroimaging experiment indicated that ABCC9 genotype is associated with cerebral blood flow impairment; in a convenience sample from Alzheimer's Disease Neuroimaging Initiative (n = 15, homozygous individuals), non-risk genotype carriers showed higher global cerebral blood flow compared to risk genotype carriers. We conclude that brain arteriolosclerosis is associated with altered cognitive status and a novel vascular genetic risk factor.
| S-EPMC5363738 | biostudies-literature
Project description:The blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed arteriolosclerosis) is common in the brains of older people and is associated with lacunar infarcts, leukoaraiosis, and vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the plasma proteins fibrinogen and immunoglobulin G, which are assumed to reflect blood-brain barrier dysfunction, in deep gray matter (DGM; anterior caudate-putamen) and deep subcortical white matter (DWM) in the brains of a well-characterized cohort of donated brains with minimal Alzheimer disease pathology (Braak Stages 0-II) (n = 84; aged 65 years or older). Morphometric measures of fibrinogen labeling were compared between people with neuropathologically defined SVD and aged control subjects. Parenchymal cellular labeling with fibrinogen and immunoglobulin G was detectable in DGM and DWM in many subjects (>70%). Quantitative measures of fibrinogen were not associated with SVD in DGM or DWM; SVD severity was correlated between DGM and DWM (p < 0.0001). Fibrinogen in DGM showed a modest association with a history of hypertension; DWM fibrinogen was associated with dementia and cerebral amyloid angiopathy (all p < 0.05). In DWM, SVD was associated with leukoaraiosis identified in life (p < 0.05), but fibrinogen was not. Our data suggest that, in aged brains, plasma extravasation and hence local blood-brain barrier dysfunction are common but do not support an association with SVD.
| S-EPMC4209852 | biostudies-literature
Project description:Background and purposeThere are few studies of spinal microvascular pathologies in older adults. We characterized spinal cord microvascular pathologies and examined their associations with other spinal and brain postmortem indices and parkinsonism in older adults.MethodsWe documented 3 features of microvascular pathologies in spinal cord and brain specimens from 165 deceased older participants. We also measured spinal white matter pallor. Parkinsonian signs were assessed with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. We examined the associations of spinal arteriolosclerosis with other spinal and brain postmortem indices and parkinsonism proximate to death using regression models which controlled for age and sex.ResultsMicroinfarcts and cerebral amyloid angiopathy were not observed within the spinal cord parenchyma. Spinal arteriolosclerosis was observed at all spinal levels (C7, T7, L4, S4) examined and was more severe posteriorly than anteriorly (posterior: 4.3, SD=0.72 versus anterior: 3.9, SD=0.74; t=14.58; P<0.001). Arteriolosclerosis was more severe in the spinal cord than in the brain (cord: 4.10, SD=0.70; brain: 3.5, SD=0.98; t=10.39; P<0.001). The severity of spinal arteriolosclerosis was associated with spinal white matter pallor (r=0.47; P<0.001). Spinal arteriolosclerosis accounted for ≈3% of the variation in parkinsonism in models controlling for age, sex, brain arteriolosclerosis, and cerebrovascular disease pathologies. Further models showed that the association of spinal arteriolosclerosis and parkinsonism was not mediated via spinal white matter pallor.ConclusionsAlthough the regional distribution of microvascular pathologies varies within the central nervous system, spinal arteriolosclerosis is common and may contribute to the severity of spinal white matter pallor and parkinsonism in older adults.
| S-EPMC5659359 | biostudies-literature
Project description:BackgroundRecent genetic studies of stroke and related risk factors have identified a growing number of susceptibility loci; however, the relationship of these alleles to ischemic stroke is unknown. The challenge in finding reproducible loci of ischemic stroke susceptibility may be in part related to the etiologic heterogeneity in clinically defined stroke subtypes. In this study, we tested whether known single nucleotide polymorphisms (SNPs) associated with stroke or putative stroke risk factors are associated with neuropathologically defined micro- or macroscopic infarcts and with arteriolosclerosis.MethodsMeasures of neuropathology and genotyping were available from 755 deceased participants from the Religious Orders Study and the Rush Memory and Aging Project. All donated brains were examined by a board-certified neuropathologist using standardized protocol for the presence of microscopic infarct, macroscopic infarct and arteriolosclerosis (lipohyalinosis). In primary analysis, 74 candidate SNPs previously associated (p < 5 × 10(-8)) with ischemic stroke or known risk factors, including atrial fibrillation (AF), hypertension, diabetes, low-density lipoprotein (LDL) level and carotid artery stenosis, were evaluated for association with neuropathologic endpoints. We performed a secondary exploratory analysis to include 93 additional SNPs associated with putative ischemic stroke risk factors including SNPs associated with high-density lipoprotein (HDL), triglyceride serum levels, myocardial infarction (MI), coronary artery disease and cerebral white matter disease. Regression models relating SNPs to cerebrovascular neuropathology were adjusted for age at death, gender and cohort membership.ResultsThe strongest associations seen for both macroscopic and microscopic infarcts were risk variants associated with diabetes. The diabetes risk variant rs7578326 located near the IRS1 locus was associated with both macroscopic (OR = 0.73, p = 0.011) and microscopic (OR = 0.71, p = 0.009) infarct pathology. Another diabetes susceptibility locus (rs12779790) located between the calcium/calmodulin-dependent protein kinase ID (CAMK1D) and cell division cycle 123 homolog (CDC123) genes is also associated with both macroscopic (OR = 1.40, p = 0.0292) and microscopic infarcts (OR = 1.43, p = 0.0285). The diabetes risk variant rs864745 within JAZF1 was associated with arteriolosclerosis (OR = 0.80, p = 0.014). We observed suggestive associations with the diabetes risk variant rs7961581 (p = 0.038; between TSPAN8 and LGR5) and rs5215 (p = 0.043; KCNJ11), the LDL risk variant rs11206510 (p = 0.045; PCSK9), as well as the AF risk locus ZFHX3. The CDKN2A/B locus (rs2383207, 9p21), identified initially as a susceptibility allele for MI and recently implicated in large vessel stroke, was associated with macroscopic infarct pathology in our autopsy cohort (OR = 1.26, p = 0.031).ConclusionOur results suggest replication of the candidate CDKN2A/B stroke susceptibility locus with directly measured macroscopic stroke neuropathology, and further implicate several diabetes and other risk variants with secondary, pleiotropic associations to stroke-related pathology in our autopsy cohort. When coupled with larger sample sizes, cerebrovascular neuropathologic phenotypes will likely be powerful tools for the genetic dissection of susceptibility for ischemic stroke.
| S-EPMC3871868 | biostudies-literature
Project description:ImportanceChronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impacts, including those from US football, that presents with cognitive and neuropsychiatric disturbances that can progress to dementia. Pathways to dementia in CTE are unclear and likely involve tau and nontau pathologic conditions.ObjectiveTo investigate the association of white matter rarefaction and cerebrovascular disease with dementia in deceased men older than 40 years who played football and had CTE.Design, setting, and participantsThis cross-sectional study involves analyses of data from the ongoing Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Study, which is conducted via and included brain donors from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank between 2008 and 2017. An original sample of 224 men who had played football and were neuropathologically diagnosed with CTE was reduced after exclusion of those younger than 40 years and those missing data.ExposuresThe number of years of football play as a proxy for repetitive head impacts.Main outcomes and measuresNeuropathological assessment of white matter rarefaction and arteriolosclerosis severity (on a scale of 0-3, where 3 is severe); number of infarcts, microinfarcts, and microbleeds; and phosphorylated tau accumulation determined by CTE stage and semiquantitative rating of dorsolateral frontal cortex (DLFC) neurofibrillary tangles (NFTs) (none or mild vs moderate or severe). Informant-based retrospective clinical interviews determined dementia diagnoses via diagnostic consensus conferences.ResultsA total of 180 men were included. The mean (SD) age of the sample at death was 67.9 (12.7) years. Of 180, 120 [66.7%]) were found to have had dementia prior to death. Moderate to severe white matter rarefaction (84 of 180 [46.6%]) and arteriolosclerosis (85 of 180 [47.2%]) were common; infarcts, microinfarcts, and microbleeds were not. A simultaneous equations regression model controlling for age and race showed that more years of play was associated with more severe white matter rarefaction (β, 0.16 [95% CI, 0.02-0.29]; P = .03) and greater phosphorylated tau accumulation (DLFC NFTs: β, 0.15 [95% CI, 0.004-0.30]; P = .04; CTE stage: β, 0.27 [95% CI, 0.14-0.41]; P < .001). White matter rarefaction (β, 0.16 [95% CI, 0.02-0.29]; P = .03) and DLFC NFTs (β, 0.16 [95% CI, 0.03-0.28]; P = .01) were associated with dementia. Arteriolosclerosis and years of play were not associated, but arteriolosclerosis was independently associated with dementia (β, 0.21 [95% CI, 0.07-0.35]; P = .003).Conclusions and relevanceAmong older men who had played football and had CTE, more years of football play were associated with more severe white matter rarefaction and greater DLFC NFT burden. White matter rarefaction, arteriolosclerosis, and DLFC NFTs were independently associated with dementia. Dementia in CTE is likely a result of neuropathologic changes, including white matter rarefaction and phosphorylated tau, associated with repetitive head impact and pathologic changes not associated with head trauma, such as arteriolosclerosis.
| S-EPMC6686769 | biostudies-literature
Project description:ObjectiveWe sought to evaluate early clinical differences between cerebral arteriolosclerosis (pARTE), Alzheimer disease (pAD), and AD with arteriolosclerosis (ADARTE).MethodsUsing National Alzheimer's Coordinating Center neuropathology diagnoses, we defined pARTE (n=21), pAD (n=203), and ADARTE (n=158) groups. We compared demographics, medical history, psychometrics, neuropsychiatric symptoms, and apolipoprotein E (APOE) allele variants across neuropathology groups. Retrospective timepoints were first evaluation with Global Clinical Dementia Rating (CDR) score of 0.5 and 1.0, via the CDR Dementia Staging Instrument, corresponding to mild cognitive impairment (MCI) and mild dementia, respectively.ResultsIn MCI, clinical differences were minimal but pARTE subjects were older, had later onset cognitive decline, and progressed less severely than pAD. In mild dementia, pAD subjects were younger and had earlier onset of decline. Neuropsychiatric (depression) and psychometric (Logical Memory Delayed Recall, Trails B) differences also emerged between the groups. In MCI, APOE4 associated with worse Logical Memory Delayed Recall in pAD and ADARTE. In mild dementia, APOE4 associated with better animal fluency in pAD, but with better Trails A performance and more neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire) in ADARTE.ConclusionsDifferences between pARTE, pAD, and ADARTE emerge at mild dementia rather than MCI. APOE4 has varied cognitive and psychiatric impact dependent on neuropathology group and stage.
| S-EPMC7904566 | biostudies-literature
Project description:The purpose of this study is to determine whether AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles make radiation work more effectively in the treatment of patients with brain metastases that are more difficult to control with stereotactic radiation alone.
| 2378535 | ecrin-mdr-crc