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Alzheimer Disease and Associated...We sought to evaluate early clinical differences between cerebral arteriolosclerosis (pARTE), Alzheimer disease (pAD), and AD with arteriolosclerosis (ADARTE).
OBJECTIVE
We sought to evaluate early clinical differences between cerebral arteriolosclerosis (pARTE), Alzheimer disease (pAD), and AD with arteriolosclerosis (ADARTE).
METHODS
Using 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.
RESULTS
In 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.
CONCLUSIONS
Differences 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.
Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Apolipoprotein E4; Cognitive Dysfunction; Disease Progression; Female; Humans; Intracranial Arteriosclerosis; Male; Mental Status and Dementia Tests; Neuropathology; Neuropsychological Tests; Retrospective Studies
PubMed: 32925200
DOI: 10.1097/WAD.0000000000000411 -
NeuroImage. Clinical 2021Brain 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...
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/.
Topics: Aged; Alzheimer Disease; Arteriolosclerosis; Brain; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Reproducibility of Results
PubMed: 34330087
DOI: 10.1016/j.nicl.2021.102768 -
Archives of Pathology & Laboratory... Aug 2009Arteriosclerosis is the vascular disease that is the leading cause of mortality in industrialized countries. Currently, there are 3 lesions within the broader category... (Review)
Review
CONTEXT
Arteriosclerosis is the vascular disease that is the leading cause of mortality in industrialized countries. Currently, there are 3 lesions within the broader category of arteriosclerosis: atherosclerosis, Mönckeberg medial calcific sclerosis, and arteriolosclerosis.
OBJECTIVE
In this review, we discuss the history of the terminology and current classification of arteriosclerosis and problems with the current classification. We also discuss recently described new arterial lesions that are not in the current classification.
DATA SOURCES
In spite of the prevalence and importance of arteriosclerotic vascular disease, and the widespread use of the current terminology, there are major problems with the current classification: (1) the current classification has an inconsistent naming convention, (2) the classification fails to use terms that accurately describe the lesions, and (3) important arterial lesions are absent from the classification. In addition, although the terms arteriosclerosis and atherosclerosis describe different lesions, these terms are often used interchangeably.
CONCLUSION
Consideration should be given for a new more inclusive and accurate classification of "arteriosclerotic" lesions that more accurately reflects the pathology of these important vascular lesions.
Topics: Arteries; Arteriosclerosis; Humans; Terminology as Topic
PubMed: 19653731
DOI: 10.5858/133.8.1309 -
Stroke Jan 2020
Review
Topics: Arteriolosclerosis; Cerebral Small Vessel Diseases; Humans; Ischemia; Magnetic Resonance Imaging; Mutation; Stroke
PubMed: 31752611
DOI: 10.1161/STROKEAHA.119.024151 -
Archives of Pathology & Laboratory... Mar 2013Nodular, intercapillary glomerulosclerotic lesions resembling Kimmelstiel-Wilson nodules commonly observed in diabetic nephropathy can also be seen in patients without... (Review)
Review
CONTEXT
Nodular, intercapillary glomerulosclerotic lesions resembling Kimmelstiel-Wilson nodules commonly observed in diabetic nephropathy can also be seen in patients without any clinical history or evidence of diabetes.
OBJECTIVES
To discuss the pathobiology of lesions reminiscent of diabetes nephropathy, including light-chain deposition disease, amyloidosis, immunotactoid nephropathy, the membranoproliferative form of glomerulonephritis, and idiopathic nodular glomerulosclerosis, and how to differentiate them from diabetic nephropathy.
DATA SOURCES
Published literature and authors' personal experience.
CONCLUSIONS
The well-formed, intercapillary, nodular mesangial lesions, along with thickened glomerular basement membranes and tubular basement membranes, and hyaline arteriolosclerosis are virtually pathognomic of diabetic nephropathy. However, the pathologist must exclude lesions reminiscent of diabetic nephropathy by performing special stains on histologic sections, immunofluorescence, and electron microscopic studies.
Topics: Diabetic Nephropathies; Humans; Kidney
PubMed: 23451746
DOI: 10.5858/arpa.2012-0243-RA -
The American Journal of Pathology Nov 2021Alzheimer disease (AD) is the most common cause of dementia. Biological definitions of AD are limited to the cerebral burden of amyloid β plaques, neurofibrillary... (Review)
Review
Alzheimer disease (AD) is the most common cause of dementia. Biological definitions of AD are limited to the cerebral burden of amyloid β plaques, neurofibrillary pathology, and neurodegeneration. However, current evidence suggests that various features of small vessel disease (SVD) are part of and covertly modify both sporadic and familial AD. Neuroimaging studies suggest that white matter hyperintensities explained by vascular mechanisms occurs frequently in the AD spectrum. Recent advances have further emphasized that frontal periventricular and posterior white matter hyperintensities are associated with cerebral amyloid angiopathy in familial AD. Although whether SVD markers precede the classically recognized biomarkers of disease is debatable, post-mortem studies show that SVD pathology incorporating small cortical and subcortical infarcts, microinfarcts, microbleeds, perivascular spacing, and white matter attenuation is commonly found in sporadic as well as in mutation carriers with confirmed familial AD. Age-related cerebral vessel pathologies such as arteriolosclerosis and cerebral amyloid angiopathy modify progression or worsen risk by shifting the threshold for cognitive impairment and AD dementia. The incorporation of SVD as a biomarker is warranted in the biological definition of AD. Therapeutic interventions directly reducing the burden of brain amyloid β have had no major impact on the disease or delaying cognitive deterioration, but lowering the risk of vascular disease seems the only rational approach to tackle both early- and late-onset AD dementia.
Topics: Alzheimer Disease; Cerebral Small Vessel Diseases; Humans
PubMed: 34331941
DOI: 10.1016/j.ajpath.2021.07.004 -
The Lancet. Neurology Mar 2012The association between small but still visible lacunar infarcts and cognitive decline has been established by population-based radiological and pathological studies.... (Review)
Review
The association between small but still visible lacunar infarcts and cognitive decline has been established by population-based radiological and pathological studies. Microscopic examination of brain sections shows even smaller but substantially more numerous microinfarcts, the focus of this Review. These lesions often result from small vessel pathologies such as arteriolosclerosis or cerebral amyloid angiopathy. They typically go undetected in clinical-radiological correlation studies that rely on conventional structural MRI, although the largest acute microinfarcts can be detected by diffusion-weighted imaging. In view of their high numbers and widespread distribution, microinfarcts could directly disrupt important cognitive networks and thus account for some of the neurological dysfunction associated with lesions visible on conventional MRI such as lacunar infarcts and white matter hyperintensities. Standardised neuropathological assessment criteria and the development of non-invasive means of detection during life would be major steps towards understanding the causes and consequences of otherwise macroscopically invisible microinfarcts.
Topics: Brain; Brain Infarction; Cognition Disorders; Humans; Nerve Fibers, Myelinated
PubMed: 22341035
DOI: 10.1016/S1474-4422(11)70307-6 -
Stroke Feb 2016Although several forms of sleep disruption are associated with stroke, few studies have examined the relationship between sleep and histopathologic measures of...
BACKGROUND AND PURPOSE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
Sleep fragmentation is associated with arteriolosclerosis and subcortical infarcts in older adults.
Topics: Actigraphy; Aged, 80 and over; Arteriolosclerosis; Autopsy; Brain Infarction; Cerebral Amyloid Angiopathy; Cerebral Infarction; Female; Humans; Independent Living; Intracranial Arteriosclerosis; Logistic Models; Male; Odds Ratio; Severity of Illness Index; Sleep Deprivation
PubMed: 26768207
DOI: 10.1161/STROKEAHA.115.011608 -
Neurology Dec 2022Topographical distribution of white matter hyperintensities (WMH) are hypothesized to vary by cerebrovascular risk factors. We used an unbiased pattern discovery...
BACKGROUND AND OBJECTIVES
Topographical distribution of white matter hyperintensities (WMH) are hypothesized to vary by cerebrovascular risk factors. We used an unbiased pattern discovery approach to identify distinct WMH spatial patterns and investigate their association with different WMH etiologies.
METHODS
We performed a cross-sectional study on participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) to identify spatially distinct WMH distribution patterns using voxel-based spectral clustering analysis of aligned WMH probability maps. We included all participants from the ADNI Grand Opportunity/ADNI 2 study with available baseline 2D-FLAIR MRI scans, without history of stroke or presence of infarction on imaging. We evaluated the associations of these WMH spatial patterns with vascular risk factors, amyloid-β PET, and imaging biomarkers of cerebral amyloid angiopathy (CAA), characterizing different forms of cerebral small vessel disease (CSVD) using multivariable regression. We also used linear regression models to investigate whether WMH spatial distribution influenced cognitive impairment.
RESULTS
We analyzed MRI scans of 1,046 ADNI participants with mixed vascular and amyloid-related risk factors (mean age 72.9, 47.7% female, 31.4% hypertensive, 48.3% with abnormal amyloid PET). We observed unbiased partitioning of WMH into 5 unique spatial patterns: deep frontal, periventricular, juxtacortical, parietal, and posterior. Juxtacortical WMH were independently associated with probable CAA, deep frontal WMH were associated with risk factors for arteriolosclerosis (hypertension and diabetes), and parietal WMH were associated with brain amyloid accumulation, consistent with an Alzheimer disease (AD) phenotype. Juxtacortical, deep frontal, and parietal WMH spatial patterns were associated with cognitive impairment. Periventricular and posterior WMH spatial patterns were unrelated to any disease phenotype or cognitive decline.
DISCUSSION
Data-driven WMH spatial patterns reflect discrete underlying etiologies including arteriolosclerosis, CAA, AD, and normal aging. Global measures of WMH volume may miss important spatial distinctions. WMH spatial signatures may serve as etiology-specific imaging markers, helping to resolve WMH heterogeneity, identify the dominant underlying pathologic process, and improve prediction of clinical-relevant trajectories that influence cognitive decline.
Topics: Humans; Female; Male; Alzheimer Disease; White Matter; Cross-Sectional Studies; Arteriolosclerosis; Cerebral Amyloid Angiopathy; Magnetic Resonance Imaging; Cognitive Dysfunction; Cerebral Small Vessel Diseases
PubMed: 36123127
DOI: 10.1212/WNL.0000000000201186 -
Stroke and Vascular Neurology Aug 2023Cerebrovascular parenchymal damage is prevalent in ageing brains; however, its vascular aetiology has not been fully elucidated. In addition to the underlying role of...
BACKGROUND AND PURPOSE
Cerebrovascular parenchymal damage is prevalent in ageing brains; however, its vascular aetiology has not been fully elucidated. In addition to the underlying role of sclerotic arterioles, the correlation between collagenised venules has not been clarified. Here, we aimed to investigate the associations between microvascular injuries, including arteriolosclerosis and venular collagenosis, and related parenchymal damages in ageing brains, to investigate the underlying correlations.
METHODS
We evaluated arteriolosclerosis and venular collagenosis in 7 regions from 27 autopsy cases with no history of stroke or brain tumour. The correlations between the ratio of arteriolosclerosis, venular collagenosis and the severity of cerebrovascular parenchymal damage, including lacunes, microinfarcts, myelin loss, and parenchymal and perivascular haemosiderin deposits, were assessed.
RESULTS
Arteriolosclerosis and venular collagenosis became more evident with age. Arteriolosclerosis was associated with lacunes (p=0.004) and brain parenchymal haemosiderin deposits in the superior frontal cortex (p=0.024) but not with leukoaraiosis severity. Venular collagenosis was not associated with the number of lacunes or haemosiderin, while white matter generally became paler with severe venular collagenosis in the periventricular (β=-0.430, p=0.028) and deep white matter (β=-0.437, p=0.025).
CONCLUSION
Our findings imply an important role for venular lesions in relation to microvessel-related parenchymal damage which is different from that for arteriolosclerosis. Different underlying mechanisms of both cerebral arterioles and venules require further investigation.
Topics: Humans; Venules; Arteriolosclerosis; Autopsy; Hemosiderin; Brain
PubMed: 36581493
DOI: 10.1136/svn-2022-001924