Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy

Objectives: To test the hypotheses that peak skeletonized mean diffusivity (PSMD), a measure of cerebral white matter microstructural disruption, is 1) increased in patients with cerebral amyloid angiopathy (CAA) compared to normal control (NC), mild cognitive impairment (MCI), and Alzheimer’s disea...

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Main Authors: Cheryl R. McCreary, Andrew E. Beaudin, Arsenije Subotic, Angela M. Zwiers, Ana Alvarez, Anna Charlton, Bradley G. Goodyear, Richard Frayne, Eric E. Smith
Format: Article
Language:English
Published: Elsevier 2020-01-01
Series:NeuroImage: Clinical
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213158220301170
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author Cheryl R. McCreary
Andrew E. Beaudin
Arsenije Subotic
Angela M. Zwiers
Ana Alvarez
Anna Charlton
Bradley G. Goodyear
Richard Frayne
Eric E. Smith
author_facet Cheryl R. McCreary
Andrew E. Beaudin
Arsenije Subotic
Angela M. Zwiers
Ana Alvarez
Anna Charlton
Bradley G. Goodyear
Richard Frayne
Eric E. Smith
author_sort Cheryl R. McCreary
collection DOAJ
description Objectives: To test the hypotheses that peak skeletonized mean diffusivity (PSMD), a measure of cerebral white matter microstructural disruption, is 1) increased in patients with cerebral amyloid angiopathy (CAA) compared to normal control (NC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD); 2) associated with neuropsychological test performance among CAA patients; and 3) increased more quickly over one year in CAA than in AD, MCI, and NC. Methods: Ninety-two participants provided a medical history, completed a neuropsychological assessment, and had a magnetic resonance (MR) exam including diffusion tensor imaging (DTI) from which PSMD was calculated. A 75-minute neuropsychological test battery was used to derive domain scores for memory, executive function, and processing speed. Multivariable analyses controlling for age and sex (and education, for cognitive outcomes) were used to test the study hypotheses. Results: PSMD was higher in the CAA group (mean 4.97 × 10−4 mm2/s) compared to NC (3.25 × 10−4 mm2/s), MCI (3.62 × 10−4 mm2/s) and AD (3.89 × 10−4 mm2/s) groups (p < .01). Among CAA patients, higher PSMD was associated with slower processing speed (estimated −0.22 standard deviation (SD) change in processing speed z score per SD increase in PSMD, 95% CI −0.42 to −0.03, p = .03), higher WMH volume [β = 0.74, CI 0.48 to 1.00], and higher CAA SVD score [β = 0.68, CI 0.24 to 1.21] but was not associated with MMSE, executive function, memory, CMB count, or cortical thickness. PSMD increased over 1-year in all groups (p < .01) but without rate differences between groups (p = .66). Conclusions: PSMD, a simple marker of diffuse global white matter heterogeneity, is increased in CAA. Our findings further support a role for white matter disruption in causing cognitive impairment in CAA.
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spelling doaj.art-702a187bbf78478db3961888e2d998022022-12-21T17:24:51ZengElsevierNeuroImage: Clinical2213-15822020-01-0127102280Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathyCheryl R. McCreary0Andrew E. Beaudin1Arsenije Subotic2Angela M. Zwiers3Ana Alvarez4Anna Charlton5Bradley G. Goodyear6Richard Frayne7Eric E. Smith8Corresponding author at: University of Calgary, HSC 2946, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.; Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Seaman Family MR Research Centre, Foothills Medical Centre, Alberta Health Sciences, Calgary, Alberta, CanadaDepartments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Seaman Family MR Research Centre, Foothills Medical Centre, Alberta Health Sciences, Calgary, Alberta, CanadaDepartments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Seaman Family MR Research Centre, Foothills Medical Centre, Alberta Health Sciences, Calgary, Alberta, CanadaDepartments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Seaman Family MR Research Centre, Foothills Medical Centre, Alberta Health Sciences, Calgary, Alberta, CanadaDepartments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Seaman Family MR Research Centre, Foothills Medical Centre, Alberta Health Sciences, Calgary, Alberta, CanadaDepartments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Seaman Family MR Research Centre, Foothills Medical Centre, Alberta Health Sciences, Calgary, Alberta, CanadaDepartments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Seaman Family MR Research Centre, Foothills Medical Centre, Alberta Health Sciences, Calgary, Alberta, CanadaDepartments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Seaman Family MR Research Centre, Foothills Medical Centre, Alberta Health Sciences, Calgary, Alberta, CanadaDepartments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Seaman Family MR Research Centre, Foothills Medical Centre, Alberta Health Sciences, Calgary, Alberta, CanadaObjectives: To test the hypotheses that peak skeletonized mean diffusivity (PSMD), a measure of cerebral white matter microstructural disruption, is 1) increased in patients with cerebral amyloid angiopathy (CAA) compared to normal control (NC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD); 2) associated with neuropsychological test performance among CAA patients; and 3) increased more quickly over one year in CAA than in AD, MCI, and NC. Methods: Ninety-two participants provided a medical history, completed a neuropsychological assessment, and had a magnetic resonance (MR) exam including diffusion tensor imaging (DTI) from which PSMD was calculated. A 75-minute neuropsychological test battery was used to derive domain scores for memory, executive function, and processing speed. Multivariable analyses controlling for age and sex (and education, for cognitive outcomes) were used to test the study hypotheses. Results: PSMD was higher in the CAA group (mean 4.97 × 10−4 mm2/s) compared to NC (3.25 × 10−4 mm2/s), MCI (3.62 × 10−4 mm2/s) and AD (3.89 × 10−4 mm2/s) groups (p < .01). Among CAA patients, higher PSMD was associated with slower processing speed (estimated −0.22 standard deviation (SD) change in processing speed z score per SD increase in PSMD, 95% CI −0.42 to −0.03, p = .03), higher WMH volume [β = 0.74, CI 0.48 to 1.00], and higher CAA SVD score [β = 0.68, CI 0.24 to 1.21] but was not associated with MMSE, executive function, memory, CMB count, or cortical thickness. PSMD increased over 1-year in all groups (p < .01) but without rate differences between groups (p = .66). Conclusions: PSMD, a simple marker of diffuse global white matter heterogeneity, is increased in CAA. Our findings further support a role for white matter disruption in causing cognitive impairment in CAA.http://www.sciencedirect.com/science/article/pii/S2213158220301170Cerebral amyloid angiopathyAlzheimer’s diseaseCognitionDiffusionMagnetic resonance imaging
spellingShingle Cheryl R. McCreary
Andrew E. Beaudin
Arsenije Subotic
Angela M. Zwiers
Ana Alvarez
Anna Charlton
Bradley G. Goodyear
Richard Frayne
Eric E. Smith
Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy
NeuroImage: Clinical
Cerebral amyloid angiopathy
Alzheimer’s disease
Cognition
Diffusion
Magnetic resonance imaging
title Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy
title_full Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy
title_fullStr Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy
title_full_unstemmed Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy
title_short Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy
title_sort cross sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy
topic Cerebral amyloid angiopathy
Alzheimer’s disease
Cognition
Diffusion
Magnetic resonance imaging
url http://www.sciencedirect.com/science/article/pii/S2213158220301170
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