J Stroke.  2021 May;23(2):223-233. 10.5853/jos.2020.04280.

Decreased Basal Ganglia Volume in Cerebral Amyloid Angiopathy

• Fotiadis P
• Pasi M
• Charidimou A
• Warren AD
• Schwab KM
• Alzheimer’s Disease Neuroimaging Initiative
• Rosand J
• Grond Jvd
• Buchem MAv
• Viswanathan A
• Gurol ME
• Greenberg SM

• KMID: 2516411
• DOI: http://doi.org/10.5853/jos.2020.04280

Abstract

Background and Purpose
Cerebral amyloid angiopathy (CAA) is a common pathology of the leptomeningeal and cortical small vessels associated with hemorrhagic and non-hemorrhagic brain injury. Given previous evidence for CAA-related loss of cortical thickness and white matter volume, we hypothesized that CAA might also cause tissue loss in the basal ganglia.
Methods
We compared basal ganglia volumes expressed as a percentage of total intracranial volume (pBGV) of non-demented patients with sporadic and hereditary CAA to age-matched healthy control (HC) and Alzheimer’s disease (AD) cohorts.
Results
Patients with sporadic CAA had lower pBGV (n=80, 1.16%±0.14%) compared to HC (n=80, 1.30%±0.13%, P<0.0001) and AD patients (n=80, 1.23%±0.11%, P=0.001). Similarly, patients with hereditary CAA demonstrated lower pBGV (n=25, 1.26%±0.17%) compared to their matched HC (n=25, 1.36%±0.15%, P=0.036). Using a measurement of normalized basal ganglia width developed for analysis of clinical-grade magnetic resonance images, we found smaller basal ganglia width in patients with CAA-related lobar intracerebral hemorrhage (ICH; n=93, 12.35±1.47) compared to age-matched patients with hypertension-related deep ICH (n=93, 13.46±1.51, P<0.0001) or HC (n=93, 15.45±1.22, P<0.0001). Within the sporadic CAA research cohort, decreased basal ganglia volume was independently correlated with greater cortical gray matter atrophy (r=0.45, P<0.0001), increased basal ganglia fractional anisotropy (r=–0.36, P=0.001), and worse performance on language processing (r=0.35, P=0.003), but not with cognitive tests of executive function or processing speed.
Conclusions
These findings suggest an independent effect of CAA on basal ganglia tissue loss, indicating a novel mechanism for CAA-related brain injury and neurologic dysfunction.

Keyword

Cerebral amyloid angiopathy; Basal ganglia; Atrophy; Diffusion; Cognition

Figure

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  Figure 1. Visual basal ganglia atrophy scale. (A) Paradigm illustrating the three widths of interest: estimated caudate width (indicated in blue), estimated putamen-pallidum distance (indicated in green), and estimated hemispheric intracranial distance (indicated in red). (B) Definitions of the three widths of interest. (C) Definition of the normalized basal ganglia visual atrophy scale.

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  Figure 2. Regional basal ganglia atrophy in patients with sporadic cerebral amyloid angiopathy (CAA) versus healthy controls. The colored (green and red) regions represent masks of the (A) putamen, (B) caudate nucleus, (C) globus pallidus, or (D) nucleus accumbens. Red regions represent the locations where patients with sporadic CAA demonstrated significant atrophy when compared to age-matched healthy controls (P<0.05, corrected for multiple comparisons). Green regions represent the locations with no significant difference between the compared groups. The Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) FMRIB’s Integrated Registration and Segmentation Tool (FIRST) for automatic segmentation of subcortical structures was used to generate the results. All results were manually checked to ensure accuracy, and the statistical maps were corrected for total intracranial volume.

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  Figure 3. Regional basal ganglia atrophy in patients with sporadic cerebral amyloid angiopathy (CAA) versus patients with Alzheimer’s disease (AD). The colored (green, red, and blue) regions represent masks of the (A) putamen, (B) caudate nucleus, (C) globus pallidus, or (D) nucleus accumbens. Red regions represent the locations where patients with sporadic CAA demonstrated significant atrophy when compared to age-matched patients with AD, blue regions the locations where patients with AD demonstrated significant atrophy when compared to their matched CAA patients (P<0.05, corrected for multiple comparisons). Green regions represent the locations with no significant difference between the compared groups. The Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) FMRIB’s Integrated Registration and Segmentation Tool (FIRST) for automatic segmentation of subcortical structures was used to generate the results. All results were manually checked to ensure accuracy, and the statistical maps were corrected for total intracranial volume.

Reference

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