Myelin loss in white matter hyperintensities and normal-appearing white matter of cognitively impaired patients: a quantitative synthetic magnetic resonance imaging study
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White matter hyperintensities (WMHs) are implicated in the etiology of dementia. The underlying pathology of WMHs involves myelin and axonal loss due to chronic ischemia. We investigated myelin loss in WMHs and normal-appearing white matter (NAWM) in patients with various degrees of cognitive impairment using quantitative synthetic magnetic resonance imaging (MRI).
We studied 99 consecutive patients with cognitive complaints who underwent 3 T brain MRI between July 2016 and August 2017. Myelin partial volume maps were generated with synthetic MRI. Region-of-interest–based analysis was performed on these maps to compare the myelin partial volumes of NAWM and periventricular and deep WMHs. The effects of myelin partial volume of NAWMs on clinical cognitive function were evaluated using multivariate linear regression analysis.
WMHs were present in 30.3% of patients. Myelin partial volume in NAWM was lower in patients with WMHs than in those without (37.5 ± 2.7% vs. 39.9 ± 2.4%, p < 0.001). In patients with WMHs, myelin partial volume was highest in NAWMs (median [interquartile range], 37.2% [35.5–39.0%]), followed by deep WMHs (7.2% [3.2–10.5%]) and periventricular WMHs (2.1% [1.1–3.9%], p < 0.001). After adjusting for sex and education years, myelin partial volume in NAWMs was associated with the Clinical Dementia Rating Scale Sum of Box (β = -0.189 [95% CI, -0.380 to -0.012], p = 0.031).
Myelin loss occurs in both NAWM and WMHs of cognitively impaired patients. Synthetic MRI-based myelin quantification may be a useful imaging marker of cognitive dysfunction in patients with cognitive complaints.
• Quantitative synthetic MRI allows simultaneous acquisition of conventional MRI and myelin quantification without additional scanning time.
• Normal-appearing and hyperintense white matter demonstrate myelin loss in cognitively impaired patients.
• This myelin loss partially explains cognitive dysfunction in patients with cognitive complaints.
KeywordsCognitive dysfunction Dementia Myelin sheath Synthetic magnetic resonance imaging White matter
Clinical Dementia Rating Scale Sum of Boxes
Gray matter fraction
Mini-Mental Status Examination
Normal-appearing white matter
White matter fraction
White matter hyperintensities
This research was presented as a scientific exhibit at the ECR 2018 (C-1637) and awarded a Certificate of Merit.
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (no.2017R1A2B4010634) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI18C1038).
Compliance with ethical standards
The scientific guarantor of this publication is Won-Jin Moon.
Conflict of interest
The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.
Statistics and biometry
No complex statistical methods were necessary for this paper.
Written informed consent was waived by the Institutional Review Board.
Institutional Review Board approval was obtained.
• Cross-sectional study
• Performed at one institution
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