scholarly journals White matter atrophy in cerebral amyloid angiopathy

Neurology ◽  
2020 ◽  
Vol 95 (5) ◽  
pp. e554-e562 ◽  
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.

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”.

Abstract 6: The Effect of Vascular Amyloid on White Matter Disease is Mediated by Vascular Dysfunction in Cerebral Amyloid Angiopathy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Elif Gokcal ◽  
Mitchell J Horn ◽  
Alex A Becker ◽  
Alvin S Das ◽  
Kristin Schwab ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Amyloid Angiopathy ◽  
Vascular Dysfunction ◽  
Study Cohort ◽  
Amyloid Angiopathy ◽  
White Matter Disease ◽  
Amyloid Pet ◽  
Intracranial Volume ◽  
Amyloid Load ◽  
Cerebral Amyloid

Background: Cerebral amyloid angiopathy (CAA) is associated with white matter hyperintensities (WMH) but the physiopathological mechanisms remain unclear. We hypothesized that the relationship between vascular amyloid load and WMH is mediated by vascular dysfunction. Methods: The study cohort included 38 non-demented probable CAA patients who underwent advanced multimodal structural and functional MRI (fMRI) and amyloid PET scans. White matter hyperintensity volume was quantified using FreeSurfer and expressed as a percent of total intracranial volume (pWMHv). Time-to-peak [TTP] of blood oxygen level-dependent [BOLD] response to visual stimulation using fMRI was used as an established measure of vascular dysfunction. Mean cortical Pittsburg Compound B uptake representing amyloid load was calculated. A bootstrapping procedure was used to test the mediation hypothesis adjusting for age, sex, and presence of intracerebral hemorrhage (ICH). Results: Of 38 patients with CAA (mean age 70±7.1, 86.8% male), 25 (65.8%) had ICH, while the remaining 13 patients (34.2%) presented with multiple strictly cortical microbleeds. Higher amyloid load correlated with prolonged TTP response (r=0.373, p=0.021) and higher pWMHv (r=0.337, p=0.039), and prolonged TTP response correlated with higher pWMHv (r=0.485, p=0.002). Amyloid load no longer predicted pWMHv (p=0.254) after controlling for TTP. In the bootstrapping model, TTP response had a significant indirect effect (ab=0.977, 95% CI: 0.15-2.42), showing that the association between amyloid load and pWMHv is mediated by TTP. Discussion: Our findings confirm the hypothesis that the effect of vascular amyloid load on the extent of white matter disease is mediated by vascular dysfunction in patients with CAA. Amyloid lowering strategies might prevent pathophysiological processes leading to vascular dysfunction, therefore limiting ischemic brain injury.

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

Stroke ◽  
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.

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

Stroke ◽  
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.

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 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 Cerebral Amyloid Angiopathy: Multiple neurolgic problems

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.

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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