Lacunes, Microinfarcts, and Vascular Dysfunction in Cerebral Amyloid Angiopathy

Neurology ◽  
2021 ◽  
Vol 96 (12) ◽  
pp. e1646-e1654
Author(s):  
Elif Gokcal ◽  
Mitchell J. Horn ◽  
Susanne J. van Veluw ◽  
Aina Frau-Pascual ◽  
Alvin S. Das ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Regression Models ◽  
Cox Regression ◽  
Vascular Dysfunction ◽  
Blood Oxygen Level Dependent ◽  
White Matter Hyperintensity ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid ◽  
Relationship Of ◽  
The Relationship

ObjectiveTo analyze the relationship of lacunes with cortical cerebral microinfarcts (CMIs), to assess their association with vascular dysfunction, and to evaluate their effect on the risk of incident intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA).MethodsThe count and topography of lacunes (deep/lobar), CMIs, and white matter hyperintensity (WMH) volume were retrospectively analyzed in a prospectively enrolled CAA cohort that underwent high-resolution research MRIs. The relationship of lacunes with CMIs and other CAA-related markers including time to peak (TTP) of blood oxygen level–dependent signal, an established measure of vascular dysfunction, was evaluated in multivariate models. Adjusted Cox regression models were used to investigate the relationship between lacunes and incident ICH.ResultsThe cohort consisted of 122 patients with probable CAA without dementia (mean age, 69.4 ± 7.6 years). Lacunes were present in 31 patients (25.4%); all but one were located in lobar regions. Cortical CMIs were more common in patients with lacunes compared to patients without lacunes (51.6% vs 20.9%, p = 0.002). TTP was not associated with either lacunes or CMIs (both p > 0.2) but longer TTP response independently correlated with higher WMH volume (p = 0.001). Lacunes were associated with increased ICH risk in univariate and multivariate Cox regression models (p = 0.048 and p = 0.026, respectively).ConclusionsOur findings show a high prevalence of lobar lacunes, frequently coexisting with CMIs in CAA, suggesting that these 2 lesion types may be part of a common spectrum of CAA-related infarcts. Lacunes were not related to vascular dysfunction but predicted incident ICH, favoring severe focal vessel involvement rather than global ischemia as their mechanism.

scholarly journals Distribution of lacunes in cerebral amyloid angiopathy and hypertensive small vessel disease

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2162-2168 ◽  
Author(s):  
Marco Pasi ◽  
Gregoire Boulouis ◽  
Panagiotis Fotiadis ◽  
Eitan Auriel ◽  
Andreas Charidimou ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Close Relationship ◽  
Cerebral Amyloid ◽  
Highly Correlated ◽  
The Relationship

Objective:To evaluate whether the burden of deep and lobar lacunes differs between patients with intracerebral hemorrhage (ICH) with definite/probable cerebral amyloid angiopathy (CAA) per the Boston criteria and hypertensive small vessel disease (HTN-SVD; ICH in basal ganglia, thalami, brainstem).Methods:We defined lobar and deep lacunes similar to the topographic distribution used for ICH and cerebral microbleeds (CMBs). We then compared their distribution between patients with CAA-ICH and those with strictly deep CMB and ICH (HTN-ICH). The independent associations of lacune location with the diagnosis of CAA-ICH and HTN-ICH were evaluated with multivariable models. The relationship between lobar lacunes and white matter hyperintensity (WMH) volume was evaluated by means of partial correlation analyses adjusted for age and a validated visual scale.Results:In our final cohort of 316 patients with ICH, lacunes were frequent (24.7%), with similar rates in 191 patients with CAA and 125 with HTN-ICH (23% vs 27.2%, p = 0.4). Lobar lacunes were more commonly present in CAA (20.4% vs 5.7%, p < 0.001), while deep lacunes were more frequent in HTN-ICH (15.2% vs 2.1%, p < 0.001). After correction for demographics and clinical and neuroimaging markers of SVD, lobar lacunes were associated with CAA (p = 0.003) and deep lacunes with HTN-ICH (p < 0.001). Lobar lacunes in 80% of the cases were at least in contact with WMH, and after adjustment for age, they were highly correlated to WMH volume (r = 0.42, p < 0.001).Conclusions:Lobar lacunes are associated with CAA, whereas deep lacunes are more frequent in HTN-SVD. Lobar lacunes seem to have a close relationship with WMH, suggesting a possible common origin.

Abstract 47: White Matter Atrophy in Cerebral Amyloid Angiopathy

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Panagiotis Fotiadis ◽  
Aaron Schultz ◽  
Trey Hedden ◽  
Sergi Martinez-Ramirez ◽  
Yael Reijmer ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Amyloid Angiopathy ◽  
Cortical Thickness ◽  
Tissue Loss ◽  
White Matter Hyperintensity ◽  
Aging Brain ◽  
Amyloid Angiopathy ◽  
Intracranial Volume ◽  
White Matter Volume ◽  
Cerebral Amyloid

Background/Purpose: Cerebral Amyloid Angiopathy (CAA) leads to leukoaraiosis, lacunar infarcts and cortical tissue loss. We hypothesized that CAA is also associated with white matter atrophy (WMA). Methods: We have compared volumetric multimodal MRIs from 72 prospectively enrolled non-demented patients with probable CAA (per Boston criteria), to 3 other well-studied cohorts: 289 Healthy Controls (HC) from the Harvard Aging Brain (HAB) study, 231 HC and 198 patients with AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Validated FreeSurfer algorithms were used to calculate White Matter Volume (WMV), white matter hyperintensity volume (WMHv), and cortical thickness. Microbleeds (MBs) were counted on SWI-MRI. Measures were obtained from the contralateral hemisphere if intracerebral hemorrhage present. All volumes were corrected for total intracranial volume (ICV), so reported as percent of ICV. Results: The CAA patients were significantly younger (mean age: 70.1) compared to both HC cohorts (ADNI-HC: 76.0, p<0.001, HAB-HC: 73.8, p < 0.001), and to patients with AD (75.5, p < 0.001). Despite being younger, patients with CAA presented significantly lower global WMV (28% ± 2.6) than both ADNI-HC (29.2% ± 2.2, p < 0.001), HAB-HC (29.0% ± 2.5, p = 0.001), and patients with AD (28.7% ± 2.2, p = 0.02) [Figure]. The association persisted after correcting for age, gender and WMHv. Within the CAA cohort, there was a negative correlation between WMV and lobar MB counts (rho = -0.26, p = 0.03), it remained significant after correcting for age, gender, WMHv (p=0.016). There were no significant associations however between WMV and neither WMHv, nor cortical thickness (both p>0.2). Conclusions: Patients with CAA show WMA when compared to older HC and AD. WMA independently correlates with MBs, a marker of CAA severity. Consistent spatial patterns of atrophy especially in posterior regions when compared to both HC and AD [Figure] might represent the “WMA signature of CAA”.

scholarly journals Advances in cerebral amyloid angiopathy imaging

2019 ◽  
Vol 12 ◽  
pp. 175628641984411 ◽  
Author(s):  
Szu-Ju Chen ◽  
Hsin-Hsi Tsai ◽  
Li-Kai Tsai ◽  
Sung-Chun Tang ◽  
Bo-Chin Lee ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Imaging Techniques ◽  
White Matter Hyperintensity ◽  
Superficial Siderosis ◽  
Clinical Aspects ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Imaging Studies ◽  
Cerebral Amyloid

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease caused by β -amyloid (Aβ) deposition at the leptomeningeal vessel walls. It is a common cause of spontaneous intracerebral hemorrhage and a frequent comorbidity in Alzheimer’s disease. The high recurrent hemorrhage rate in CAA makes it very important to recognize this disease to avoid potential harmful medication. Imaging studies play an important role in diagnosis and research of CAA. Conventional computed tomography and magnetic resonance imaging (MRI) methods reveal anatomical alterations, and remains as the most reliable tool in identifying CAA according to modified Boston criteria. The vascular injuries of CAA result in both hemorrhagic and ischemic manifestations and related structural changes on MRI, including cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity, MRI-visible perivascular spaces, and cortical microinfarcts. As imaging techniques advance, not only does the resolution of conventional imaging improve, but novel skills in functional and molecular imaging studies also enable in vivo analysis of vessel physiological changes and underlying pathology. These modern tools help in early detection of CAA and may potentially serve as sensitive outcome markers in future clinical trials. In this article, we reviewed past studies of CAA focusing on utilization of various conventional and novel imaging techniques in both research and clinical aspects.

scholarly journals Cerebrovascular reactivity in cerebral amyloid angiopathy, Alzheimer disease, and mild cognitive impairment

Neurology ◽  
2020 ◽  
Vol 95 (10) ◽  
pp. e1333-e1340 ◽  
Author(s):  
Aaron R. Switzer ◽  
Ikreet Cheema ◽  
Cheryl R. McCreary ◽  
Angela Zwiers ◽  
Anna Charlton ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Alzheimer Disease ◽  
Cerebral Amyloid Angiopathy ◽  
Response Amplitude ◽  
Cerebrovascular Reactivity ◽  
White Matter Hyperintensity ◽  
Amyloid Angiopathy ◽  
Bold Response ◽  
Cerebral Amyloid

ObjectiveTo assess cerebrovascular reactivity in response to a visual task in participants with cerebral amyloid angiopathy (CAA), Alzheimer disease (AD), and mild cognitive impairment (MCI) using fMRI.MethodsThis prospective cohort study included 40 patients with CAA, 22 with AD, 27 with MCI, and 25 healthy controls. Each participant underwent a visual fMRI task using a contrast-reversing checkerboard stimulus. Visual evoked potentials (VEPs) were used to compare visual cortex neuronal activity in 83 participants. General linear models using least-squares means, adjusted for multiple comparisons with the Tukey test, were used to estimate mean blood oxygen level–dependent (BOLD) signal change during the task and VEP differences between groups.ResultsAfter adjustment for age and hypertension, estimated mean BOLD response amplitude was as follows: CAA 1.88% (95% confidence interval [CI] 1.60%–2.15%), AD 2.26% (1.91%–2.61%), MCI 2.15% (1.84%–2.46%), and control 2.65% (2.29%–3.00%). Only patients with CAA differed from controls (p = 0.01). In the subset with VEPs, group was not associated with prolonged latencies or lower amplitudes. Lower BOLD amplitude response was associated with higher white matter hyperintensity (WMH) volumes in CAA (for each 0.1% lower BOLD response amplitude, the WMH volume was 9.2% higher, 95% CI 6.0%–12.4%) but not other groups (p = 0.002 for interaction) when controlling for age and hypertension.ConclusionsMean visual BOLD response amplitude was lowest in participants with CAA compared to controls, without differences in VEP latencies and amplitudes. This suggests that the impaired visual BOLD response is due to reduced vascular reactivity in CAA. In contrast to participants with CAA, the visual BOLD response amplitude did not differ between those with AD or MCI and controls.

scholarly journals White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy

Neurology ◽  
2016 ◽  
Vol 86 (6) ◽  
pp. 505-511 ◽  
Author(s):  
Andreas Charidimou ◽  
Gregoire Boulouis ◽  
Kellen Haley ◽  
Eitan Auriel ◽  
Ellis S. van Etten ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Amyloid Angiopathy ◽  
White Matter Hyperintensity ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

Intracerebral hemorrhage due to cerebral amyloid angiopathy

1985 ◽  
Vol 63 (6) ◽  
pp. 965-969 ◽  
Author(s):  
Norbert Roosen ◽  
Jean-Jacques Martin ◽  
Christian De La Porte ◽  
Michel Van Vyve
Keyword(s):  
Intracerebral Hemorrhage ◽  
Cerebral Amyloid Angiopathy ◽  
Clinicopathological Features ◽  
Amyloid Angiopathy ◽  
Correct Treatment ◽  
Content Type ◽  
Cerebral Amyloid ◽  
Occipital Lobes ◽  
The Relationship ◽  
Fine Print

✓ The case is presented of a 59-year-old man with cerebral amyloid angiopathy and three consecutive hemorrhages in the occipital lobes. The clinicopathological features and the relationship to Alzheimer's dementia are discussed. The correct treatment of intracerebral hemorrhage related to cerebral amyloid angiopathy is a matter of controversy.

Abstract P442: The Association of Amyloid and Tau Burden With Centrum Semiovale Perivascular Spaces in Cerebral Amyloid Angiopathy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Elif Gokcal ◽  
Alex A Becker ◽  
Mitchell J Horn ◽  
Alvin S Das ◽  
Kristin Schwab ◽  
...  
Keyword(s):  
Regression Model ◽  
Cerebral Amyloid Angiopathy ◽  
Structural Mri ◽  
Ordinal Regression ◽  
White Matter Hyperintensity ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Centrum Semiovale ◽  
Ordinal Regression Model ◽  
Cerebral Amyloid

Background: The mechanisms linking cerebral amyloid angiopathy (CAA) to enlarged perivascular spaces in centrum semiovale (CSO-EPVS) and whether other Alzheimer’s Disease (AD) pathologies might affect CSO-EPVS are unclear. We hypothesized that amyloid but not tau load would independently correlate with CSO-EPVS in CAA. Methods: Fifty prospectively enrolled nondemented probable CAA patients underwent high-resolution structural MRI, Pittsburgh compound B (PiB, for amyloid), and 18 F-flortaucipir (FTP, for tau) PET imaging. Microbleeds (all lobar, LMB) were counted and white matter hyperintensity volume (WMH) was quantified. CSO-EPVS were counted on T 2 -MRI sequence and graded using a previously validated scale (range 0-4). A multivariate ordinal regression model was used to assess the independent associations between CSO-EPVS and mean cortical amyloid as well as tau deposition, after adjusting for relevant covariates. Results: Patients had a mean age of 69.3±7.2. Age, sex, presence of hypertension, intracerebral hemorrhage (ICH), LMB counts, and WMH were not associated with CSO-EPVS grades (p>0.2 for all comparisons). Higher PiB uptake significantly correlated with increased CSO-EPVS (rho=0.45, p=0.001). Higher FTP showed a trend for correlation with CSO-EPVS (rho=0.26, p=0.069). In an ordinal regression model with CSO-EPVS grade as the dependent variable and both amyloid and tau levels included as predictors along with covariates presented above, the association of CSO-EPVS remained significant with higher PiB uptake (β=3.97, 95%CI 1.1-6.8, p=0.007) but not with FTP uptake (p=0.167). Conclusion: Results of this study suggest that CSO-EPVS is independently associated with amyloid but not with tau deposition in CAA. CSO-EPVS was not associated with age or classical vascular risk factors or presence of ICH. Our results support the view that vascular amyloid but not other AD pathologies such as tau might contribute to EPVS in patients with CAA.

Δείκτες παρακολούθησης και πρόγνωσης στην ιδιοπαθή πνευμονική ίνωση

2013 ◽  
Author(s):  
Χριστίνα Τριανταφυλλίδου
Keyword(s):  
Survival Analysis ◽  
Gas Exchange ◽  
Regression Models ◽  
Research Council ◽  
Medical Research Council ◽  
Cox Regression ◽  
Exertional Dyspnea ◽  
Functional Parameters ◽  
Relationship Of ◽  
The Relationship

Background: In Idiopathic Pulmonary Fibrosis (IPF) irreversibly progressive fibrosingparenchymal damage, leads to defects in mechanics and gas exchange, manifesting withdisabling exertional dyspnea. Previous studies have shown a relationship betweenfibroblast foci (FF) profusion and disease severity and survival. We hypothesized arelationship between Medical Research Council (MRC) dyspnea scale with FF, and arelationship between FF and functional parameters and survival.Methods: We retrospectively reviewed 24 histologically documented IPF patients.Profusion of FF was semiquantitatively evaluated by two scores, Brompton andMichigan. Survival analysis was performed by fitting Cox regression models toexamine the relationship of the two scores with survival and the non-parametricSpearman correlation coefficient was calculated to describe the relationships of FFscores with dyspnea scores and functional parameters.Results: No statistically significant correlation between FF scores and the MRC scoreswas observed (p = 0.96 and p = 0.508 respectively). No significant correlation betweenFF scores and survival (p = 0.438 and p = 0.861 respectively) or any functionalparameter was observed.Conclusions: The lack of relationship between the MRC dyspnea scale and the FFmight relate to the fact that dyspnea in IPF better reflects the overall of lung damageand its related consequences on mechanics and gas exchange whereas FF, one of itshistological hallmarks, may not reflect its entire histology derangement also constrainedby the geographically limited sampled tissue. This might be also valid for the observedlack of association between FF and survival or functional parameters.

scholarly journals β-Amyloid in CSF

Neurology ◽  
2016 ◽  
Vol 88 (2) ◽  
pp. 169-176 ◽  
Author(s):  
Ellis S. van Etten ◽  
Marcel M. Verbeek ◽  
Jeroen van der Grond ◽  
Ronald Zielman ◽  
Sanneke van Rooden ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Clinical Symptoms ◽  
White Matter Hyperintensity ◽  
Superficial Siderosis ◽  
Csf Biomarkers ◽  
Amyloid Angiopathy ◽  
Cross Sectional ◽  
Mutation Carriers ◽  
Β Amyloid ◽  
Cerebral Amyloid

Objective:To investigate CSF biomarkers in presymptomatic and symptomatic mutation carriers with hereditary cerebral hemorrhage with amyloidosis–Dutch type (HCHWA-D), a model for sporadic cerebral amyloid angiopathy, and to determine the earliest deposited form of β-amyloid (Aβ).Methods:HCHWA-D mutation carriers and controls were enrolled in the cross-sectional EDAN (Early Diagnosis of Amyloid Angiopathy Network) study. The HCHWA-D group was divided into symptomatic carriers with a previous intracerebral hemorrhage and presymptomatic carriers. CSF concentrations of Aβ40, Aβ42, total tau, and phosphorylated tau181 proteins were compared to those of controls of a similar age. Correlations between CSF biomarkers, MRI markers, and age were investigated with multivariate linear regression analyses.Results:We included 10 symptomatic patients with HCHWA-D (mean age 55 ± 6 years), 5 presymptomatic HCHWA-D carriers (mean age 36 ± 13 years), 31 controls <50 years old (mean age 31 ± 7 years), and 50 controls ≥50 years old (mean age 61 ± 8 years). After correction for age, CSF Aβ40 and Aβ42 were significantly decreased in symptomatic carriers vs controls (median Aβ40 1,386 vs 3,867 ng/L, p < 0.001; median Aβ42 289 vs 839 ng/L, p < 0.001) and in presymptomatic carriers vs controls (median Aβ40 3,501 vs 4,684 ng/L, p = 0.011; median Aβ42 581 vs 1,058 ng/L, p < 0.001). Among mutation carriers, decreasing CSF Aβ40 was associated with higher lobar microbleed count (p = 0.010), increasing white matter hyperintensity volume (p = 0.008), and presence of cortical superficial siderosis (p = 0.02).Conclusions:Decreased levels of CSF Aβ40 and Aβ42 occur before HCHWA-D mutation carriers develop clinical symptoms, implicating vascular deposition of both Aβ species as early steps in cerebral amyloid angiopathy pathogenesis. CSF Aβ40 and Aβ42 may serve as preclinical biomarkers of cerebral amyloid angiopathy pathology.

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