Abstract TP441: Neurovascular Coupling is Impaired in Cerebral Amyloid Angiopathy

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Stefano Peca ◽  
Cheryl R McCreary ◽  
Emily Donaldson ◽  
Karla Sanchez ◽  
Anna Charlton ◽  
...  
Keyword(s):  
White Matter ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
White Matter Lesion ◽  
Motor Task ◽  
Neurovascular Coupling ◽  
Occipital Lobe ◽  
Amyloid Angiopathy ◽  
Bold Response ◽  
Cerebral Amyloid

Introduction: Cerebral amyloid angiopathy (CAA) is marked by accumulation of vascular beta-amyloid which is toxic to smooth muscle cells. An animal study and a pilot study in humans suggest decreased vasodilation in CAA. We studied patients with CAA and matched controls to determine whether neurovascular coupling is impaired in CAA. Methods: Patients with CAA and controls underwent task-related fMRI with a visual task (viewing a flashing alternating checkerboard pattern) or a motor task (tapping the fingers of the dominant hand) using a block design, and visual evoked potentials (VEPs). CAA patients were diagnosed by Boston criteria and had normal corrected visual acuity, no visual field deficits and no paresis of the dominant arm. Controls were recruited by community advertising and were matched by gender and age (±5 years) to CAA cases. Results: Eighteen CAA patients (12 M, 6F; 72±7 yrs) and eighteen controls (12 M, 6F; 70±7 yrs) were studied. For the visual task, CAA patients had reduced activity in the occipital lobe (Figure) and lower amplitude of the BOLD response vs. controls (28% reduced, p=0.005). By contrast, for the motor task CAA patients had a similar response of the primary motor cortex vs. controls (9.6% reduced BOLD response, p=0.53). VEP P100 latencies and amplitudes did not differ between CAA and controls (p=0.49 and p=0.74). Lower visual cortex BOLD amplitudes were correlated with greater white matter lesion volumes in CAA (r=-0.66, p=0.003). Conclusions: Neurovascular coupling is impaired in the occipital lobe in CAA. BOLD signal amplitudes are reduced despite normal evoked potentials, suggesting impaired vasodilation. The association with white matter lesion volume raises the possibility that impaired vasodilation may be involved in the pathogenesis of these lesions. BOLD responses in the primary motor cortex in CAA were not reduced, likely reflecting the known posterior predominance of CAA with lesser involvement of the frontal lobe.

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 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 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 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 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.

Motor cortex excitability and fatigue in multiple sclerosis: a transcranial magnetic stimulation study

2005 ◽  
Vol 11 (3) ◽  
pp. 316-321 ◽  
Author(s):  
J Liepert ◽  
D Mingers ◽  
C Heesen ◽  
T Bäumer ◽  
C Weiller
Keyword(s):  
Multiple Sclerosis ◽  
Transcranial Magnetic Stimulation ◽  
Motor Cortex ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Motor Task ◽  
Time Interval ◽  
Membrane Excitability ◽  
Motor Cortex Excitability ◽  
Fatigue Severity

We investigated electrophysiological correlates of fatigue in patients with multiple sclerosis (MS). Transcranial magnetic stimulation (TMS) was used to explore motor excitability in three groups of subjects: MS patients with fatigue (MS-F), MS patients without fatigue (MS-NF) and healthy control subjects. All participants had to perform a fatiguing hand-grip exercise. TMS was performed prior to and after the exercise. Prior to the motor task, MS-F patients had less inhibition in the primary motor cortex compared to both other groups. Postexercise, intracortical inhibition was still reduced in the MS-F patients compared to the MS-NF patients. In MS-F patients the postexercise time interval for normalization of the motor threshold was correlated with the fatigue severity. We conclude that MS patients with fatigue have an impairment of inhibitory circuits in their primary motor cortex. The results also indicate that fatigue severity is associated with an exercise-induced reduction of membrane excitability.

scholarly journals The BOLD response in primary motor cortex and supplementary motor area during kinesthetic motor imagery based graded fMRI neurofeedback

NeuroImage ◽  
2019 ◽  
Vol 184 ◽  
pp. 36-44 ◽  
Author(s):  
David M.A. Mehler ◽  
Angharad N. Williams ◽  
Florian Krause ◽  
Michael Lührs ◽  
Richard G. Wise ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Motor Imagery ◽  
Primary Motor Cortex ◽  
Supplementary Motor Area ◽  
Motor Area ◽  
Bold Response

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

Corticospinal tract integrity is related to primary motor cortex thinning in relapsing–remitting multiple sclerosis

2015 ◽  
Vol 21 (14) ◽  
pp. 1771-1780 ◽  
Author(s):  
Niels Bergsland ◽  
Maria Marcella Laganà ◽  
Eleonora Tavazzi ◽  
Matteo Caffini ◽  
Paola Tortorella ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Motor Cortex ◽  
Linear Regression ◽  
Multiple Linear Regression ◽  
Primary Motor Cortex ◽  
Corticospinal Tract ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Background: The relationship between white matter injury and cortical atrophy development in relapsing–remitting multiple sclerosis (RRMS) remains unclear. Objectives: To investigate the associations between corticospinal tract integrity and cortical morphology measures of the primary motor cortex in RRMS patients and healthy controls. Methods: 51 RRMS patients and 30 healthy controls underwent MRI examination for cortical reconstruction and assessment of corticospinal tract integrity. Partial correlation and multiple linear regression analyses were used to investigate the associations of focal and normal appearing white matter (NAWM) injury of the corticospinal tract with thickness and surface area measures of the primary motor cortex. Relationships between MRI measures and clinical disability as assessed by the Expanded Disability Status Scale and disease duration were also investigated. Results: In patients only, decreased cortical thickness was related to increased corticospinal tract NAWM mean, axial and radial diffusivities in addition to corticospinal tract lesion volume. The final multiple linear regression model for PMC thickness retained only NAWM axial diffusivity as a significant predictor (adjusted R2= 0.270, p= 0.001). Clinical measures were associated with NAWM corticospinal tract integrity measures. Conclusions: Primary motor cortex thinning in RRMS is related to alterations in connected white matter and is best explained by decreased NAWM integrity.

Sign in / Sign up

Export Citation Format

Share Document