Myelin Loss in White Matter Hyperintensities and Normal-Appearing White Matter of Cognitively Impaired Patients: A Quantitative Synthetic Magnetic Resonance Imaging Study

Abstract

Objectives: 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).

Methods: 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.

Results: 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).

Conclusion: 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.

Key points: • 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.