Peak width of skeletonized mean diffusivity in cerebral amyloid angiopathy: Spatial signature, cognitive, and neuroimaging associations

Maria Clara Zanon Zotin; Dorothee Schoemaker; Nicolas Raposo; Valentina Perosa; Martin Bretzner; Lukas Sveikata; Qi Li; Susanne J van Veluw; Mitchell J Horn; Mark R Etherton; Andreas Charidimou; M Edip Gurol; Steven M Greenberg; Marco Duering; Antonio Carlos Dos Santos; Octavio M Pontes-Neto; Anand Viswanathan

doi:10.3389/fnins.2022.1051038

Peak width of skeletonized mean diffusivity in cerebral amyloid angiopathy: Spatial signature, cognitive, and neuroimaging associations

Front Neurosci. 2022 Nov 11:16:1051038. doi: 10.3389/fnins.2022.1051038. eCollection 2022.

Authors

Maria Clara Zanon Zotin^{1

2}, Dorothee Schoemaker³, Nicolas Raposo⁴, Valentina Perosa⁵, Martin Bretzner^{1

6}, Lukas Sveikata^{1

7

8}, Qi Li⁹, Susanne J van Veluw¹, Mitchell J Horn¹, Mark R Etherton¹, Andreas Charidimou^{1

10}, M Edip Gurol¹, Steven M Greenberg¹, Marco Duering¹¹, Antonio Carlos Dos Santos², Octavio M Pontes-Neto¹², Anand Viswanathan¹

Affiliations

¹ J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
² Center for Imaging Sciences and Medical Physics, Department of Medical Imaging, Hematology and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
³ Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.
⁴ Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, Toulouse, France.
⁵ German Center for Neurodegenerative Disease, Magdeburg, Germany.
⁶ University of Lille, Inserm, CHU Lille, U1172 - LilNCog (JPARC) - Lille Neurosciences & Cognition, Lille, France.
⁷ Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland.
⁸ Institute of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
⁹ The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
¹⁰ Department of Neurology, Boston University School of Medicine, Boston University Medical Center, Boston, MA, United States.
¹¹ Department of Biomedical Engineering, Medical Imaging Analysis Center (MIAC), University of Basel, Basel, Switzerland.
¹² Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.

Abstract

Background: Peak width of skeletonized mean diffusivity (PSMD) is a promising diffusion tensor imaging (DTI) marker that shows consistent and strong cognitive associations in the context of different cerebral small vessel diseases (cSVD).

Purpose: Investigate whether PSMD (1) is higher in patients with Cerebral Amyloid Angiopathy (CAA) than those with arteriolosclerosis; (2) can capture the anteroposterior distribution of CAA-related abnormalities; (3) shows similar neuroimaging and cognitive associations in comparison to other classical DTI markers, such as average mean diffusivity (MD) and fractional anisotropy (FA).

Materials and methods: We analyzed cross-sectional neuroimaging and neuropsychological data from 90 non-demented memory-clinic subjects from a single center. Based on MRI findings, we classified them into probable-CAA (those that fulfilled the modified Boston criteria), subjects with MRI markers of cSVD not attributable to CAA (presumed arteriolosclerosis; cSVD), and subjects without evidence of cSVD on MRI (non-cSVD). We compared total and lobe-specific (frontal and occipital) DTI metrics values across the groups. We used linear regression models to investigate how PSMD, MD, and FA correlate with conventional neuroimaging markers of cSVD and cognitive scores in CAA.

Results: PSMD was comparable in probable-CAA (median 4.06 × 10^-4 mm²/s) and cSVD (4.07 × 10^-4 mm²/s) patients, but higher than in non-cSVD (3.30 × 10^-4 mm²/s; p < 0.001) subjects. Occipital-frontal PSMD gradients were higher in probable-CAA patients, and we observed a significant interaction between diagnosis and region on PSMD values [F(2, 87) = 3.887, p = 0.024]. PSMD was mainly associated with white matter hyperintensity volume, whereas MD and FA were also associated with other markers, especially with the burden of perivascular spaces. PSMD correlated with worse executive function (β = -0.581, p < 0.001) and processing speed (β = -0.463, p = 0.003), explaining more variance than other MRI markers. MD and FA were not associated with performance in any cognitive domain.

Conclusion: PSMD is a promising biomarker of cognitive impairment in CAA that outperforms other conventional and DTI-based neuroimaging markers. Although global PSMD is similarly increased in different forms of cSVD, PSMD's spatial variations could potentially provide insights into the predominant type of underlying microvascular pathology.

Keywords: cerebral amyloid angiopathy; cerebral small vessel disease; dementia; diffusion tensor imaging; diffusion-weighted imaging; vascular cognitive impairment.

Grants and funding

P30 AG062421/AG/NIA NIH HHS/United States