Cerebrovascular Reactivity Across the Entire Brain in Cerebral Amyloid Angiopathy

Beaudin, Andrew E.; McCreary, Cheryl R.; Mazerolle, Erin L.; Gee, Myrlene; Sharma, Breni; Subotic, Arsenije; Zwiers, Angela; Cox, Emily; Nelles, Krista; Charlton, Anna; Frayne, Richard; Ismail, Zahinoor; Beaulieu, Christian; Jickling, Glen C.; Camicioli, Richard; Pike, G. Bruce; Smith, Eric E.

doi:10.1212/wnl.0000000000200136

Cited by 23 publications

(24 citation statements)

References 51 publications

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“…To identify potential mediators of the effect of CAA on cognition compared with controls, we reviewed prior literature on neuroimaging markers associated with cognitive impairment in CAA. Based on this search, we selected this group of potential mediators: WMH volume, 4 altered white matter diffusion (represented in this study by PSMD), 7,8 CVR, 12 and cortical thickness. 6 The mediation analysis was performed in a single model, including all potential mediator variables (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

“…9 For the second group of 79 participants, CVR was measured directly as the percent increase in gray matter BOLD per mmHg increase in partial pressure of end-tidal CO 2 (PETCO 2 ) while breathing 5% CO 2 . 12 Gray matter was segmented by first skull stripping the T1-weighted images using the Brain Extraction Tool (HD-BET), 13 followed by segmentation using FSL's FMRIB Automated Segmentation Tool (FAST). 14 To make the two types of CVR measurement comparable, they were converted to z-scores based on the mean and standard deviation of the control data.…”

Section: Assessmentsmentioning

confidence: 99%

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Mediators of cognitive impairment in cerebral amyloid angiopathy

Durrani

Wang

Cox

et al. 2022

International Journal of Stroke

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Background Cerebral amyloid angiopathy (CAA) is associated with cognitive decline. CAA has diverse impacts on brain structure and function; however, the brain lesions that mediate the association of CAA with cognition are not understood well. Aims To determine the degree to which CAA neuroimaging biomarkers mediate the association of CAA with cognitive dysfunction. Methods We analyzed cross-sectional data of patients with probable CAA and controls without cognitive impairment from the Functional Assessment of Vascular Reactivity study. Neuropsychological tests were grouped into domains of memory, executive function, and processing speed. Candidate CAA neuroimaging biomarkers were pre-specified based on prior literature, consisting of white matter hyperintensity volume, peak width of skeletonized mean diffusivity (PSMD) on diffusion tensor MRI, cerebrovascular reactivity (CVR), cortical thickness, and cortical thickness in a meta-region of interest typically affected by Alzheimer’s disease (AD). Cognitive scores and neuroimaging markers were standardized and reported in relation to values in controls. Mediation analysis was used to estimate the total effect of CAA on cognition and the proportion of the total effect that was mediated by neuroimaging biomarkers, controlling for age, sex, and education. Results There were 131 participants (67 CAA and 64 control). Mean age was 72.1 ± 7.7 years, and 54.2% were women. As expected, compared to controls CAA was associated with lower cognition. In mediation analyses, CAA had direct unmediated effects of 48%, 46%, and 52% on all three cognitive domains. The association of CAA with memory was mediated by CVR and PSMD, accounting for 18% and 36% of the total effect of CAA. The association of CAA with executive function was mediated by PSMD and mean cortical thickness in the AD meta-ROI, accounting for 33% and 31% of the total effect of CAA. The association of CAA with processing speed was mediated by CVR and PSMD, accounting for 8% and 34% of the total effect of CAA. Among CAA participants, the presence of cortical superficial siderosis was associated with lower processing speed. Conclusions Altered white matter diffusivity (i.e., PSMD), CVR, and atrophy, taken together, account for about half the effect of CAA on cognition. Data access statement Anonymized data will be shared by request from a qualified investigator.

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Section: Methodsmentioning

confidence: 99%

Section: Assessmentsmentioning

confidence: 99%

Mediators of cognitive impairment in cerebral amyloid angiopathy

Durrani

Wang

Cox

et al. 2022

International Journal of Stroke

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“…Participants were enrolled in the multi-center Canadian Consortium on Neurodegeneration in Aging’s (CCNA), Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study ( Chertkow et al, 2019 ) and the Functional Assessment and Vascular Reactivity (FAVR)-II study ( Beaudin et al, 2022 ). The COMPASS-ND was approved by the research ethics boards of all the involved institutions while FAVR-II was approved at the University of Alberta and University of Calgary.…”

Section: Methodsmentioning

confidence: 99%

Dual-task gait and white matter hyperintensities in Lewy body diseases: An exploratory analysis

Fatokun

Gee

Nelles

et al. 2023

Front. Aging Neurosci.

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BackgroundParkinson’s disease (PD) and dementia with Lewy bodies (DLB) are part of a spectrum of Lewy body disorders, who exhibit a range of cognitive and gait impairments. Cognitive-motor interactions can be examined by performing a cognitive task while walking and quantified by a dual task cost (DTC). White matter hyperintensities (WMH) on magnetic resonance imaging have also been associated with both gait and cognition. Our goal was to examine the relationship between DTC and WMH in the Lewy body spectrum, hypothesizing DTC would be associated with increased WMH volume.MethodsSeventy-eight participants with PD, PD with mild cognitive impairment (PD-MCI), PD with dementia or DLB (PDD/DLB), and 20 cognitively unimpaired participants were examined in a multi-site study. Gait was measured on an electronic walkway during usual gait, counting backward, animal fluency, and subtracting sevens. WMH were quantified from magnetic resonance imaging using an automated pipeline and visual rating. A median split based on DTC was performed. Models included age as well as measures of global cognition and cardiovascular risk.ResultsCompared to cognitively unimpaired participants, usual gait speed was lower and DTC was higher in PD-MCI and PDD/DLB. Low DTC participants had higher usual gait speed. WMH burden was greater in high counting DTC participants. Frontal WMH burden remained significant after adjusting for age, cardiovascular risk and global cognition.ConclusionIncreased DTC was associated with higher frontal WMH burden in Lewy body disorders after adjusting for age, cardiovascular risk, and global cognition. Higher DTC was associated with age.

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“…The study was based on the ongoing, multi-site Functional Assessment of Vascular Reactivity (FAVR) study which consecutively recruited CAA, mild AD, and healthy control (HC) participants from Calgary and Edmonton, Canada ( Peca et al, 2013 ; McCreary et al, 2020 ; Subotic et al, 2021 ; Beaudin et al, 2022 ). All participants were ≥ 55 years of age, did not have significant neurological or psychiatric disorders, or contraindications for MRI at 3 T. Participants with CAA and AD were mainly recruited from stroke prevention and cognitive clinics, while HCs were recruited from the community through poster advertisements or from spouses of patients.…”

Section: Methodsmentioning

confidence: 99%

Subcortical volumes in cerebral amyloid angiopathy compared with Alzheimer’s disease and controls

et al. 2023

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BackgroundPrevious reports have suggested that patients with cerebral amyloid angiopathy (CAA) may harbor smaller white matter, basal ganglia, and cerebellar volumes compared to age-matched healthy controls (HC) or patients with Alzheimer’s disease (AD). We investigated whether CAA is associated with subcortical atrophy.MethodsThe study was based on the multi-site Functional Assessment of Vascular Reactivity cohort and included 78 probable CAA (diagnosed according to the Boston criteria v2.0), 33 AD, and 70 HC. Cerebral and cerebellar volumes were extracted from brain 3D T1-weighted MRI using FreeSurfer (v6.0). Subcortical volumes, including total white matter, thalamus, basal ganglia, and cerebellum were reported as proportion (%) of estimated total intracranial volume. White matter integrity was quantified by the peak width of skeletonized mean diffusivity.ResultsParticipants in the CAA group were older (74.0 ± 7.0, female 44%) than the AD (69.7 ± 7.5, female 42%) and HC (68.8 ± 7.8, female 69%) groups. CAA participants had the highest white matter hyperintensity volume and worse white matter integrity of the three groups. After adjusting for age, sex, and study site, CAA participants had smaller putamen volumes (mean differences, −0.024% of intracranial volume; 95% confidence intervals, −0.041% to −0.006%; p = 0.005) than the HCs but not AD participants (−0.003%; −0.024 to 0.018%; p = 0.94). Other subcortical volumes including subcortical white matter, thalamus, caudate, globus pallidus, cerebellar cortex or cerebellar white matter were comparable between all three groups.ConclusionIn contrast to prior studies, we did not find substantial atrophy of subcortical volumes in CAA compared to AD or HCs, except for the putamen. Differences between studies may reflect heterogeneity in CAA presenting syndromes or severity.

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Cerebrovascular Reactivity Across the Entire Brain in Cerebral Amyloid Angiopathy

Cited by 23 publications

References 51 publications

Mediators of cognitive impairment in cerebral amyloid angiopathy

Mediators of cognitive impairment in cerebral amyloid angiopathy

Dual-task gait and white matter hyperintensities in Lewy body diseases: An exploratory analysis

Subcortical volumes in cerebral amyloid angiopathy compared with Alzheimer’s disease and controls

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