Peak width of skeletonized mean diffusivity and cognitive performance in cerebral amyloid angiopathy

Mitchell J Horn; Elif Gokcal; J Alex Becker; Alvin S Das; Kristin Schwab; Maria Clara Zanon Zotin; Joshua N Goldstein; Jonathan Rosand; Anand Viswanathan; Jonathan R Polimeni; Marco Duering; Steven M Greenberg; M Edip Gurol

doi:10.3389/fnins.2023.1141007

Peak width of skeletonized mean diffusivity and cognitive performance in cerebral amyloid angiopathy

Front Neurosci. 2023 Apr 3:17:1141007. doi: 10.3389/fnins.2023.1141007. eCollection 2023.

Affiliations

¹ Department of Neurology, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA, United States.
² Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States.
³ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
⁴ Department of Medical Imaging, Hematology and Clinical Oncology, Ribeirão Preto Medical School, Center for Imaging Sciences and Medical Physics, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
⁵ Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
⁶ Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States.
⁷ Medical Image Analysis Center (MIAC), Department of Biomedical Engineering, University of Basel, Basel, Switzerland.

Abstract

Background: Cerebral Amyloid Angiopathy (CAA) is a cerebral small vessel disease that can lead to microstructural disruption of white matter (WM), which can be measured by the Peak Width of Skeletonized Mean Diffusivity (PSMD). We hypothesized that PSMD measures would be increased in patients with CAA compared to healthy controls (HC), and increased PSMD is associated with lower cognitive scores in patients with CAA.

Methods: Eighty-one probable CAA patients without cognitive impairment who were diagnosed with Boston criteria and 23 HCs were included. All subjects underwent an advanced brain MRI with high-resolution diffusion-weighted imaging (DWI). PSMD scores were quantified from a probabilistic skeleton of the WM tracts in the mean diffusivity (MD) image using a combination of fractional anisotropy (FA) and the FSL Tract-Based Spatial Statistics (TBSS) algorithm (www.psmd-marker.com). Within CAA cohort, standardized z-scores of processing speed, executive functioning and memory were obtained.

Results: The mean of age and sex were similar between CAA patients (69.6 ± 7.3, 59.3% male) and HCs (70.6 ± 8.5, 56.5% male) (p = 0.581 and p = 0.814). PSMD was higher in the CAA group [(4.13 ± 0.94) × 10^-4 mm²/s] compared to HCs [(3.28 ± 0.51) × 10^-4 mm²/s] (p < 0.001). In a linear regression model corrected for relevant variables, diagnosis of CAA was independently associated with increased PSMD compared to HCs (ß = 0.45, 95% CI 0.13-0.76, p = 0.006). Within CAA cohort, higher PSMD was associated with lower scores in processing speed (p < 0.001), executive functioning (p = 0.004), and memory (0.047). Finally, PSMD outperformed all other MRI markers of CAA by explaining most of the variance in models predicting lower scores in each cognitive domain.

Discussion: Peak Width of Skeletonized Mean Diffusivity is increased in CAA, and it is associated with worse cognitive scores supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA. As a robust marker, PSMD can be used in clinical trials or practice.

Keywords: cerebral amyloid angiopathy (CAA); cerebral small vessel disease; cognitive functions; diffusion-weighted imaging; peak width of skeletonized mean diffusivity (PSMD).

Peak width of skeletonized mean diffusivity and cognitive performance in cerebral amyloid angiopathy

Authors

Affiliations

Abstract

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