White matter integrity changes and neurocognitive functioning in adult-late onset DM1: a follow-up DTI study

Garazi Labayru,Antonio Jimenez-Marin,Miren Zulaica,Jesus M Cortes,Joana Garmendia,Jorge Villanua,Andone Sistiaga,Adolfo López De Munain,Borja Camino

doi:10.1038/s41598-022-07820-1

Abstract

Myotonic Dystrophy Type 1 (DM1) is a multisystemic disease that affects gray and white matter (WM) tissues. WM changes in DM1 include increased hyperintensities and altered tract integrity distributed in a widespread manner. However, the precise temporal and spatial progression of the changes are yet undetermined. MRI data were acquired from 8 adult- and late-onset DM1 patients and 10 healthy controls (HC) at two different timepoints over 9.06 years. Fractional anisotropy (FA) and mean diffusivity (MD) variations were assessed with Tract-Based Spatial Statistics. Transversal and longitudinal intra- and intergroup analyses were conducted, along with correlation analyses with clinical and neuropsychological data. At baseline, reduced FA and increased MD values were found in patients in the uncinate, anterior-thalamic, fronto-occipital, and longitudinal tracts. At follow-up, the WM disconnection was shown to have spread from the frontal part to the rest of the tracts in the brain. Furthermore, WM lesion burden was negatively correlated with FA values, while visuo-construction and intellectual functioning were positively correlated with global and regional FA values at follow-up. DM1 patients showed a pronounced WM integrity loss over time compared to HC, with a neurodegeneration pattern that suggests a progressive anterior–posterior disconnection. The visuo-construction domain stands out as the most sensitive neuropsychological measure for WM microstructural impairment.

Highlights

Myotonic Dystrophy Type-1 (DM1) is an inherited autosomal dominant disorder, which affects multiple systems, including the Central Nervous System (CNS)
Over a period of nearly a decade, this study has revealed a progression in whiter matter (WM) integrity impairment in adult and late onset DM1 population occurring as early as from the 40’s to the 50’s
The reduction in fractional anisotropy (FA) found at baseline in patients in comparison with healthy controls (HC) was greater at follow-up, where WM integrity was compromised throughout all the tracts and similar results were seen when assessing mean diffusivity (MD) alterations

Summary

Introduction

Myotonic Dystrophy Type-1 (DM1) is an inherited autosomal dominant disorder, which affects multiple systems (e.g., muscular, cardiovascular, respiratory, gastrointestinal, endocrine), including the Central Nervous System (CNS). Considered a rare disease, with an estimated worldwide prevalence of 0.5–18.1 per 100,000 inhabitants[1], DM1 is the most prevalent form of adult muscular dystrophy. Such prevalence is significantly higher in the geographical area of Gipuzkoa (Spain), which is considered the second most affected area in the world, with an estimated prevalence of 26.5 per 100,000 inhabitants[2]. Researchers agree that further investigation of WM pathology should be conducted with more valid and novel techniques such as Diffusion Tensor Imaging (DTI) tractography This technique, along with a set of neuropsychological measures, are potentially critical for fully characterizing the status of individuals with DM110

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