White Matter Alterations in Cerebral Amyloid Angiopathy Measured by Diffusion Tensor Imaging

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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Abstract 47: White Matter Atrophy in Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.47.suppl_1.47 ◽

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”.

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Abstract P59: Peak Width of Skeletonized Mean Diffusivity Outperforms Other Diffusion Tensor Imaging Metrics as Biomarker for Cognition in Memory-Clinic Subjects With Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.52.suppl_1.p59 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Maria Clara Zanon Zotin ◽

Dorothee Schoemaker ◽

Valentina Perosa ◽

Martin Bretzner ◽

Lukas Sveikata ◽

...

Keyword(s):

Executive Function ◽

Diffusion Tensor Imaging ◽

Linear Regression ◽

Processing Speed ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Amyloid Angiopathy ◽

Peak Width ◽

Memory Clinic ◽

Cerebral Amyloid

Introduction: Peak width of skeletonized mean diffusivity (PSMD) is a novel fully automated diffusion tensor imaging (DTI) marker that has been consistently associated with cognition in cerebral small vessel disease (SVD) cohorts, including cerebral amyloid angiopathy (CAA). We hypothesized that PSMD would be more strongly associated with cognitive performance compared to other conventional DTI metrics in our CAA sample. Methods: We recruited non-demented subjects with probable-CAA from a single-center memory-clinic cohort. We analyzed structural MRIs to compute a validated CAA burden score (0-6 points scale, based on the following MRI features: lobar microbleeds, superficial siderosis, perivascular spaces in centrum semiovale, and white matter hyperintensities). PSMD was obtained using a freely available script ( www.psmd-marker.com ). We used the same skeleton-mask to compute: mean of skeletonized mean diffusivity (mean MD) and mean of skeletonized fractional anisotropy (mean FA). We used linear regression analyses to explore relationships with CAA burden score and cognitive composite scores (processing speed, executive function, memory, and language - z-scores adjusted for age, sex and education level). Results: We included 43 subjects (mean age 74.4 ± 5.9 years; 48.8% female; PSMD median [IQR]: 4.05 [3.58 - 4.80] x 10 -4 mm 2 /s). In linear regression models adjusting for age, DTI metrics were significantly associated with CAA burden score (mean FA: β = -0.563, Adj. R 2 : 0.27; p < 0.001; mean MD: β = 0.581; Adj. R 2 : 0.32; p < 0.001; PSMD: β = 0.364, Adj. R 2 : 0.12; p = 0.018). PSMD was significantly associated with cognitive performance, specifically in the domains of executive function ( β = -0.568; Adj. R 2 : 0.25; p < 0.001) and processing speed ( β = -0.447; Adj. R 2 : 0.19; p = 0.004). Other DTI metrics were not significantly associated with cognitive scores. Conclusion: In this CAA sample, all DTI metrics were associated with CAA burden scores, however, only PSMD was significantly associated with cognition, in domains that are commonly affected in vascular cognitive impairment. Our results warrant confirmation in larger samples, but support PSMD as biomarker for cognition in CAA, outperforming other conventional DTI metrics.

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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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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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White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy

Neurology ◽

10.1212/wnl.0000000000002362 ◽

2016 ◽

Vol 86 (6) ◽

pp. 505-511 ◽

Cited By ~ 58

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

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Cerebral amyloid angiopathy-related leukoencephalopathy: Successful steroid treatment for neurological deficits and subcortical white matter lesions partly involving the cortical gray matter

Neurology and Clinical Neuroscience ◽

10.1111/ncn3.101 ◽

2014 ◽

Vol 2 (4) ◽

pp. 119-121

Author(s):

Takenobu Murakami ◽

Julia Morimoto ◽

Akihiko Hoshi ◽

Setsu Nakatani-Enomoto ◽

Masahiro Ichikawa ◽

...

Keyword(s):

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Gray Matter ◽

White Matter Lesions ◽

Subcortical White Matter ◽

Steroid Treatment ◽

Neurological Deficits ◽

Amyloid Angiopathy ◽

Cortical Gray Matter ◽

Cerebral Amyloid

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Cerebral Amyloid Angiopathy: Multiple neurolgic problems

Psychology and Mental Health Care ◽

10.31579/2637-8892/015 ◽

2017 ◽

Vol 1 (3) ◽

pp. 01-01

Author(s):

Paul Gilbert

Keyword(s):

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Clinical Symptoms ◽

Brain Biopsy ◽

Acute Onset ◽

Amyloid Angiopathy ◽

Migraine Headaches ◽

Diffuse White Matter ◽

Cerebral Amyloid ◽

Intravenous Steroids

A 72-Year-old female with a history of migraine headaches presented with an acute onset of expressive aphasia, difficulty with memory and worsening of her headaches. An MRI of the brain was done which revealed diffuse white matter T2 hyperintensities (Figures 1). Due to worsening of the patient’s clinical symptoms a repeat MRI was performed four days later that revealed multiple micro-bleeds (Figure 2), as well as a lobar hemorrhage in left temporal lobe (Figure 2). An extensive workup including HIV testing, CSF examination for infectious etiology including protein 14-3-3 and demylineating disease was negative. Paraneoplastic and autoimmune workup was also non-diagnostic. A brain biopsy was performed due to the extensive white matter disease, which revealed Cerebral Amyloid Angiopathy (CAA) with focal granulomatous angiitis. The patient was treated with intravenous steroids with no significant improvement clinically. Two months after diagnosis, her disease course has remained static, without improvement or deterioration.

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