Hypertensive Arteriopathy and Cerebral Amyloid Angiopathy in Patients with Cognitive Decline and Mixed Cerebral Microbleeds

2020 ◽  
Vol 78 (4) ◽  
pp. 1765-1774
Author(s):  
Yuichiro Ii ◽  
Hidehiro Ishikawa ◽  
Hirofumi Matsuyama ◽  
Akihiro Shindo ◽  
Keita Matsuura ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
White Matter Hyperintensity ◽  
Superficial Siderosis ◽  
Amyloid Angiopathy ◽  
Age Related ◽  
Cerebral Amyloid ◽  
Occipital Lobes

Background: Hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA) may contribute to the development of mixed cerebral microbleeds (CMBs). Recently, the total small vessel disease (SVD) scores for HA and CAA were proposed, which are determined by a combination of MRI markers to reflect overall severity of these microangiopathies. Objective: We investigated whether or not total HA-SVD and CAA-SVD scores could be used to predict overlap of HA and CAA in patients with mixed CMBs. Methods: Fifty-three subjects with mixed CMBs were retrospectively analyzed. MRI markers (CMBs, lacunes, perivascular space, white matter hyperintensity [WMH] and cortical superficial siderosis [cSS]) were assessed. The HA-SVD score and CAA-SVD score were obtained for each subject. Anterior or posterior WMH was also assessed using the age-related white matter changes scale. Results: The two scores were positively correlated (ρ= 0.449, p < 0.001). The prevalence of lobar dominant CMB distribution (p < 0.001) and lacunes in the centrum semiovale (p < 0.001) and the severity of WMH in the parieto-occipital lobes (p = 0.004) were significantly higher in the high CAA-SVD score group. cSS was found in four patients with high CAA-SVD score who showed lobar-dominant CMB distribution and severe posterior WMH. Conclusion: Mixed CMBs are mainly due to HA. Assessing both two scores may predict the overlap of HA and CAA in individuals with mixed CMBs. Patients with a high CAA-SVD score may have some degree of advanced CAA, especially when lobar predominant CMBs, severe posterior WMH, lobar lacunes, or cSS are observed.

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 The Contribution of Vascular Pathology Toward Cognitive Impairment in Older Individuals with Intermediate Braak Stage Tau Pathology

2020 ◽  
Vol 77 (3) ◽  
pp. 1005-1015 ◽  
Author(s):  
Andrew C. Robinson ◽  
Federico Roncaroli ◽  
Stephen Chew-Graham ◽  
Yvonne S. Davidson ◽  
James Minshull ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Vascular Pathology ◽  
Cognitively Impaired ◽  
Amyloid Angiopathy ◽  
Braak Stage ◽  
Age Related ◽  
Cerebral Amyloid

Background: The pathological features of Alzheimer’s disease (AD) are well described but little is known as to how both neurodegeneration and vascular changes might interact in causing cognitive impairment. Objective: The present study aims to investigate relationships between vascular and AD pathology in cognitively healthy and cognitively impaired individuals with a particular emphasis on those at intermediate Braak tau stages. Methods: We investigated the interplay between Braak tau stage and measures of vascular pathology as described by the vascular cognitive impairment neuropathology guidelines (VCING) in 185 brains from the Brains for Dementia Research programme and The University of Manchester Longitudinal Study of Cognition in Healthy Old Age. VCING asserts that at least one large (>10 mm) infarct, moderate/severe occipital leptomeningeal cerebral amyloid angiopathy, and moderate/severe arteriosclerosis in occipital white matter accurately predicts the contribution of cerebrovascular pathology to cognitive impairment. Results: We found that the extent of arteriosclerosis in the occipital white matter did not differ between cognitive groups at intermediate (III-IV) Braak stages whereas moderate/severe leptomeningeal occipital cerebral amyloid angiopathy was greater in cognitively impaired than normal individuals at Braak stage III-IV. This finding remained significant after controlling for effects of age, sex, CERAD score, Thal phase, presence/severity of primary age-related tauopathy, presence/severity of limbic-predominant age-related TDP43 encephalopathy and small vessel disease in basal ganglia. Conclusion: Interventions targeting cerebral amyloid angiopathy may contribute to delay the onset of cognitive impairment in individuals with intermediate Alzheimer’s type pathology.

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 Clinical and radiological differences between patients with probable cerebral amyloid angiopathy and mixed cerebral microbleeds

2020 ◽  
Vol 267 (12) ◽  
pp. 3602-3608 ◽  
Author(s):  
Ulf R. Jensen-Kondering ◽  
Caroline Weiler ◽  
Patrick Langguth ◽  
Naomi Larsen ◽  
Charlotte Flüh ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Cerebral Microbleeds ◽  
Superficial Siderosis ◽  
Periventricular White Matter ◽  
Amyloid Angiopathy ◽  
Imaging Features ◽  
Significant Difference ◽  
Comprehensive Comparison ◽  
Cerebral Amyloid ◽  
Cortical Superficial Siderosis

Abstract Background The key imaging features of cerebral amyloid angiopathy (CAA) are lobar, cortical, or cortico-subcortical microbleeds, macrohaemorrhages and cortical superficial siderosis (cSS). In contrast, hypertensive angiopathy is characterized by (micro) haemorrhages in the basal ganglia, thalami, periventricular white matter or the brain stem. Another distinct form of haemorrhagic microangiopathy is mixed cerebral microbleeds (mixed CMB) with features of both CAA and hypertensive angiopathy. The distinction between the two entities (CAA and mixed CMB) is clinically relevant because the risk of haemorrhage and stroke should be well balanced if oral anticoagulation is indicated in CAA patients. We aimed to comprehensively compare these two entities. Methods Patients with probable CAA according to the modified Boston criteria and mixed CMB without macrohaemorrhage were retrospectively identified from our database. Comprehensive comparison regarding clinical and radiological parameters was performed between the two cohorts. Results Patients with CAA were older (78 ± 8 vs. 74 ± 9 years, p = 0.036) and had a higher prevalence of cSS (19% vs. 4%, p = 0.027) but a lower prevalence of lacunes (73% vs. 50%, p = 0.018) and deep lacunes (23% vs. 51%, p = 0.0003) compared to patients with mixed CMB. Logistic regression revealed an association between the presence of deep lacunes and mixed CMB. The other collected parameters did not reveal a significant difference between the two groups. Conclusions CAA and mixed CMB demonstrate radiological differences in the absence of macrohaemorrhages. However, more clinically available biomarkers are needed to elucidate the contribution of CAA and hypertensive angiopathy in mixed CMB patients.

scholarly journals A case of cerebral amyloid angiopathy with reversible white matter lesions and multiple cerebral microbleeds

2012 ◽  
Vol 52 (2) ◽  
pp. 90-95 ◽  
Author(s):  
Yasushi Hosoi ◽  
Tsuyoshi Uchiyama ◽  
Mari Yoshida ◽  
Daisuke Takechi ◽  
Takako Shimizu ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Amyloid Angiopathy ◽  
White Matter Lesions ◽  
Cerebral Microbleeds ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

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.

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

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.

White Matter Perivascular Spaces Are Related to Cortical Superficial Siderosis in Cerebral Amyloid Angiopathy

Stroke ◽  
2014 ◽  
Vol 45 (10) ◽  
pp. 2930-2935 ◽  
Author(s):  
Andreas Charidimou ◽  
Rolf H. Jäger ◽  
Andre Peeters ◽  
Yves Vandermeeren ◽  
Patrice Laloux ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Amyloid Angiopathy ◽  
Superficial Siderosis ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Cerebral Amyloid ◽  
Cortical Superficial Siderosis

083 Response to immunosuppressive therapy in cerebral amyloid angiopathy-related inflammation

2018 ◽  
Vol 89 (6) ◽  
pp. A33.3-A34
Author(s):  
Jasmin Tilling ◽  
Benjamin Trewin ◽  
Stanley Levy
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Cerebral Amyloid Angiopathy ◽  
White Matter Hyperintensities ◽  
Neurological Deficits ◽  
Amyloid Angiopathy ◽  
Dramatic Improvement ◽  
Age Related ◽  
Cerebral Amyloid ◽  
The Brain

IntroductionCerebral amyloid angiopathy (CAA) is a common age-related condition characterised by amyloid beta-peptide deposition affecting the medium sized cortical and leptomeningeal arteries, arterioles and capillaries. CAA-related Inflammation (CAA-I) is an increasingly recognised variant of CAA, which is thought to be due to perivascular auto-inflammation in response to amyloid deposition. We describe the clinical course of two cases of probable CAA-I.CasesA 71 year old man presented with new-onset seizures, headaches and subacute cognitive decline. MRI of the brain demonstrated confluent subcortical T2 white matter hyperintensities and cerebral oedema, with predominantly superimposed widespread cortico-subcortical micro-haemorrhages, in keeping with the diagnosis of CAA-I. A course of immunosuppresive therapy was commenced with five days of intravenous methylprednisolone, resulting in marked radiological and clinical improvement within two weeks.A 76 year old female presented with subacute cognitive dysfunction and apraxia, and transient left-sided weakness. MRI scan of the brain initially demonstrated a right temporo-occipital infarct, leading to primary treatment for stroke, but subsequently evolved to reveal diffuse multi-lobar T2 white matter hyperintensities with leptomeningeal involvement. A provisional diagnosis of CAA-I was made and following a poor clinical response to a trial of corticosteroid therapy, treatment with intravenous cyclophosphamide was commenced.ConclusionThese cases emphasise the importance of CAA-I as part of the differential diagnosis in patients presenting with symptoms of subacute cognitive decline, seizures, headaches and focal neurological deficits, given the potential for dramatic improvement with readily accessible immunosuppressive therapies.

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