Brain Structure and Cognitive Dysfunction in Myotonic Dystrophy Type 2 (BraCE‐DM2)

Abstract

AbstractBackgroundMyotonic dystrophy type 2 (DM2) is a pleiotropic multisystemic disease. Although progressive muscle weakness is the main symptom in DM2, almost two‐third of the patients report cognitive deficits as one of the most disabling symptoms. Emerging evidence has identified tau mis‐splicing and tangle pathology in DM2, which has prompted interest in elucidating the role of tau in DM2‐related cognitive impairment. Previous studies suggest that cerebral white matter (WM) is primarily affected in DM2. However, quantitative brain imaging studies incorporate with cognitive measures are extremely limited.Method3T brain MRIs were acquired in 10 adults with DM2 and 10 gender and age‐matched controls. Brain morphometry and WM integrity were assessed using T1‐MPRAGE and diffusion tensor imaging (DTI) sequences. DTI scalars, including fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and median diffusivity (MD) were compared between groups. A comprehensive battery of cognitive and behavioral measures was performed and correlated with MRI measures (Spearman’s Correlation).ResultOf 20 participants (60% female), mean age (62.2 vs. 62.6 years) and education (16.4 vs. 17.5 years) were similar between the two groups. Compared to controls, the DM2 group showed a significant reduction in global measures of cerebral gray matter (GM) volume in both cortex and deep gray structures (mean difference, ‐0.03; p<0.01), but not the WM volume. Widespread abnormalities in DTI measures (lower FA, higher RD) were among the most robust findings in DM2 (mean differences of FA, 0.04; p<0.01 and RD, 0.00004; p<0.01), indicating that the pathology is within WM microstructures. Overall, the DM2 group scored lower than controls in all cognitive domains, particularly executive function (mean difference, ‐12.5; p = 0.04). We found a strong correlation between cerebral FA and a test of executive function (rho = 0.71, p = 0.02). Cerebral FA also showed a moderate correlation with processing speed (rho = 0.50) and apathy evaluation scale (rho = ‐0.43).ConclusionOur pilot data demonstrate robust differences of brain structure, explicitly measures of WM integrity and cerebral GM volume between the DM2 group vs. controls. The strong correlation between cerebral FA and executive function also supports the notion that WM integrity plays an important role in cognitive dysfunction in DM2.