Exploring the Contribution of Myelin Content in Normal Appearing White Matter to Cognitive Outcomes in Cerebral Small Vessel Disease

Article type: Research Article

Authors: Dao, Elizabeth^{a; b; c} | Tam, Roger^{b; d; e} | Hsiung, Ging-Yuek R.^{b; f} | ten Brinke, Lisanne^{a; b; c} | Crockett, Rachel^{a; b; c} | Barha, Cindy K.^{a; b; c} | Yoo, Youngjin^d | Al Keridy, Walid^{b; f; g} | Doherty, Stephanie H.^{a; b; c} | Laule, Cornelia^{d; h; i; j} | MacKay, Alex L.^{d; k} | Liu-Ambrose, Teresa^{a; b; c; *}

Affiliations: [a] Department of Physical Therapy, University of British Columbia (UBC), Vancouver, Canada | [b] Djavad Mowafaghian Centre for Brain Health, UBC, Vancouver, Canada | [c] Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, Canada | [d] Department of Radiology, UBC, Vancouver, Canada | [e] School of Biomedical Engineering, UBC, Vancouver, Canada | [f] Division of Neurology, UBC Hospital, Vancouver, Canada | [g] Department of Medicine, King Saud University, College of Medicine, Riyadh, Saudi Arabia | [h] Department of Pathology and Laboratory Medicine, UBC, Vancouver, Canada | [i] Department of Physics and Astronomy, UBC, Vancouver, Canada | [j] International Collaboration on Repair Discoveries, Vancouver, Canada | [k] UBC MRI Research Centre, UBC, Vancouver, Canada

Correspondence: [*] Correspondence to: Teresa Liu-Ambrose, 109-828 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada. Tel.: +1 604 875 4111/Ext. 69056; E-mail: teresa.ambrose@ubc.ca.

Abstract: Background:Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood. Objective:The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD. Methods:This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05. Results:After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (β  = –0.29, p = 0.037) and poorer working memory (β= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p > 0.132). Conclusion:Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function.

Keywords: Cerebral small vessel disease, myelin, myelin water imaging, executive functions, vascular cognitive impairment, white matter hyperintensities

DOI: 10.3233/JAD-201134

Journal: Journal of Alzheimer's Disease, vol. 80, no. 1, pp. 91-101, 2021