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

Chih-Hao Chen; Mary Klir Khnaijer; Andrew E Beaudin; Cheryl R McCreary; Myrlene Gee; Feryal Saad; Richard Frayne; Zahinoor Ismail; G Bruce Pike; Richard Camicioli; Eric E Smith

doi:10.3389/fnins.2023.1139196

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

Front Neurosci. 2023 Apr 17:17:1139196. doi: 10.3389/fnins.2023.1139196. eCollection 2023.

Authors

Chih-Hao Chen^{1

2}, Mary Klir Khnaijer¹, Andrew E Beaudin^{1

3}, Cheryl R McCreary^{1

3

4}, Myrlene Gee⁵, Feryal Saad¹, Richard Frayne^{1

3

4}, Zahinoor Ismail^{1

3

6}, G Bruce Pike^{1

3

4}, Richard Camicioli⁵, Eric E Smith^{1

3

4}

Affiliations

¹ Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
² Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
³ Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
⁴ Department of Radiology, University of Calgary, Calgary, AB, Canada.
⁵ Division of Neurology, Department of Medicine and Neurosciences and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.
⁶ Department of Psychiatry, University of Calgary, Calgary, AB, Canada.

Abstract

Background: Previous 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.

Methods: The 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.

Results: Participants 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.

Conclusion: In 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.

Keywords: FreeSurfer; atrophy; cerebral amyloid angiopathy (CAA); putamen; subcortical; volume measurements.