White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy

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”.

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

Journal of Alzheimer s Disease ◽

10.3233/jad-200992 ◽

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.

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Abstract 9: Peak Width of Skeletonized Mean Diffusivity and Cognition in Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.52.suppl_1.9 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Mitchell J Horn ◽

Elif Gokcal ◽

J. A Becker ◽

Alvin S Das ◽

Kristin Schwab ◽

...

Keyword(s):

White Matter ◽

Regression Model ◽

Cerebral Amyloid Angiopathy ◽

Mean Diffusivity ◽

Multiple Regression Model ◽

Amyloid Angiopathy ◽

Peak Width ◽

Symbol Substitution ◽

Relevant Variables ◽

Cerebral Amyloid

Background: We hypothesized that Peak Width of Skeletonized Mean Diffusivity (PSMD), an automated marker of cerebral microangiopathy representing microstructural disruption of white matter (WM), would be increased in patients with cerebral amyloid angiopathy (CAA) compared to healthy controls (HCs) and increased PSMD would be associated with lower processing speed scores (PSSs) in patients with CAA. Methods: Seventy-two nondemented probable CAA patients and 23 HCs prospectively underwent high-resolution brain MRIs and cognitive tests. PSMD scores were quantified from a probabilistic skeleton of the WM tracts as previously validated (http://www.psmd-marker.com). In subjects with intracerebral hemorrhage (ICH, n=27), ICH regions were masked and removed from the PSMD pipeline. The analyses were repeated in the non-ICH hemisphere. Raw scores of Trail Making Test-B and Symbol Substitution Test were transformed into standardized z -scores and averaged to obtain PSSs. Results: The mean age (p=0.366) and sex (p=0.811) were similar between CAA patients and HCs. PSMD was higher in the CAA group [(3.95±0.9) х 10 –4 mm 2 /s] compared to HCs [(3.32±0.6) х 10 –4 mm 2 /s] (p=0.003). This association remained significant in a linear regression model corrected for age and sex (β=0.700, 95%CI 0.3-1, p=0.001). Within the CAA cohort, higher PSMD was associated with higher WM hyperintensity volume in a multiple regression model adjusted for all relevant variables (β=0.890, 95%CI 0.7-1, p<0.001). In a regression model corrected for age, sex, years of education and presence of ICH, a lower PSS was independently associated with increased PSMD (β=-0.405, 95%CI {-0.6}-{-0.2}, p<0.001). These results did not change when the non-ICH hemisphere was used for PSMD processing. Conclusion: PSMD is increased in CAA and is associated with worse PSSs supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA.

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White matter atrophy in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000010017 ◽

2020 ◽

Vol 95 (5) ◽

pp. e554-e562 ◽

Cited By ~ 1

Author(s):

Panagiotis Fotiadis ◽

Yael D. Reijmer ◽

Susanne J. Van Veluw ◽

Sergi Martinez-Ramirez ◽

Fikret Isik Karahanoglu ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Amyloid Angiopathy ◽

Intracranial Volume ◽

White Matter Volume ◽

Cognitive Changes ◽

Important Mediator ◽

Multivariable Analyses ◽

Cerebral Amyloid

ObjectiveWe postulated that cerebral amyloid angiopathy (CAA) is associated with white matter atrophy (WMA) and that WMA can be related to cognitive changes in CAA.MethodsWhite matter volume expressed as percent of intracranial volume (pWMV) of prospectively enrolled patients without dementia diagnosed with probable CAA was compared to age-matched healthy controls (HC) and patients with Alzheimer disease (AD). Cognitive scores were also sought to understand the potential effects of WMA on cognitive function.ResultsPatients with CAA (n = 72) had significantly lower pWMV (27.97% ± 2.63) when compared to age-matched HC (n = 72; mean difference [MD], 2.38%; p < 0.0001) and patients with AD (n = 72; MD, 1.57%; p < 0.0001). Differences were most pronounced in the posterior occipital regions in both comparisons. When comparisons were restricted to groups of patients with CAA but no intracerebral hemorrhage (n = 32) or hypertension (n = 32), and age-matched HC and AD, the significant differences were unaltered. Within the CAA cohort, higher age, lobar microbleed counts, and presence of hypertension were associated with lower pWMV (p = 0.0007, p = 0.031, and p = 0.003, respectively). All associations remained independent in multivariable analyses. Within the CAA cohort, higher pWMV independently correlated with better scores of executive function.ConclusionsPatients with CAA show WMA when compared to age-matched HC and patients with AD. WMA independently correlates with the number of lobar microbleeds, a marker of CAA severity. Consistent spatial patterns of WMA especially in posterior regions might be related to CAA. The association between WMA and measures of executive function suggests that WMA might represent an important mediator of CAA-related neurologic dysfunction.

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Abstract 36: The Boston Criteria V2.0 for Cerebral Amyloid Angiopathy: Updated Criteria and Multicenter MRI-Neuropathology Validation

Stroke ◽

10.1161/str.52.suppl_1.36 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Matthew Frosch ◽

Jean-Claude Baron ◽

Marco Pasi ◽

...

Keyword(s):

White Matter ◽

Intracerebral Hemorrhage ◽

Diagnostic Accuracy ◽

Cerebral Amyloid Angiopathy ◽

Brain Mri ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Validation Sample ◽

Temporal Validation ◽

Cerebral Amyloid

Introduction: The Boston criteria are used worldwide for in vivo diagnosis of cerebral amyloid angiopathy (CAA). Given substantial advances in CAA research, we aimed to update the Boston criteria and externally validate their diagnostic accuracy across the spectrum of CAA-related presentations and across international sites. Methods: As part of an International CAA Association multicenter study, we identified patients age 50 or older with potential CAA-related clinical presentations (spontaneous intracerebral hemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathologic assessment for the diagnosis of CAA. We derived Boston criteria v2.0 by selecting MRI features to optimize diagnostic specificity and sensitivity in a pre-specified derivation sample (Boston cases 1994 to 2012, n=159), then externally validated in pre-specified temporal (Boston cases 2012-2018, n=59) and geographical (non-Boston cases 2004-2018; n=123) validation samples and compared their diagnostic accuracy to the currently used modified Boston criteria. Results: Based on exploratory analyses in the derivation sample, we derived provisional criteria for probable CAA requiring presence of at least 2 strictly lobar hemorrhagic lesions (intracerebral hemorrhage, cerebral microbleed, or cortical superficial siderosis focus) or at least 1 strictly lobar hemorrhagic lesion and 1 white matter characteristic (severe degree of visible perivascular spaces in centrum semiovale or white matter hyperintensities multispot pattern). Sensitivity/specificity of the criteria were 74.8/84.6% in the derivation sample, 92.5/89.5% in the temporal validation sample, 80.2/81.5% in the geographic validation sample, and 74.5/95.0% in cases across all samples with autopsy as the diagnostic gold standard. The v2.0 criteria for probable CAA had superior accuracy to the currently modified Boston criteria (p<0.005) in the autopsied cases. Conclusion: The Boston criteria v.2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their high specificity. Validation of the criteria across independent patient settings firmly supports their adoption into clinical practice and research.

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Advances in cerebral amyloid angiopathy imaging

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419844113 ◽

2019 ◽

Vol 12 ◽

pp. 175628641984411 ◽

Cited By ~ 2

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.

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

Neurology ◽

10.1212/wnl.0000000000010201 ◽

2020 ◽

Vol 95 (10) ◽

pp. e1333-e1340 ◽

Cited By ~ 1

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.

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

Rinsho Shinkeigaku ◽

10.5692/clinicalneurol.52.90 ◽

2012 ◽

Vol 52 (2) ◽

pp. 90-95 ◽

Cited By ~ 1

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

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

Neurology ◽

10.1212/wnl.0000000000004007 ◽

2017 ◽

Vol 88 (23) ◽

pp. 2162-2168 ◽

Cited By ~ 43

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.

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