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

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.

Neurocognitive disorder in Myotonic dystrophy type 1

“…Nevertheless, this finding is consistent with results from cross-sectional and longitudinal studies, indicating that patients with late onset DM1 perform worse and show a higher rate of cognitive decline as compared to subgroups with an earlier onset of the disease [ 15 , 22 , 25 ]. Furthermore, a recent study by Labayru et al [ 53 ] on a small sample of patients with late onset DM1 (n = 8) also showed pronounced white matter integrity loss over time, suggesting neurodegeneration in this phenotype. Other disorders potentially linked to brain dysfunction, such as myocardial infarction and stroke, were found in 24 % of patients with late-onset DM1 (see Table 1 ).…”

In Vivo Parieto-Occipital White Matter Metabolism Is Correlated with Visuospatial Deficits in Adult DM1 Patients

“…On the other hand, visuospatial functioning is heavily reliant on the integrity of the parietal lobe and its connections with the occipital regions [ 62 , 63 , 64 ]. Neuroimaging studies in DM1 patients showed consistently a substantial impairment in visuospatial and visuoconstructional abilities that were significantly correlated with WM abnormalities and cortical volume loss as demonstrated by advanced morphological and diffusivity techniques such as voxel-based morphometry VBM and TBSS [ 5 , 18 , 26 , 65 , 66 , 67 , 68 ]. Here we showed that these abilities are also related to metabolic alterations that can be present within the NAWM.…”

“…Both visuospatial and visuo-constructional impairments are considered distinctive features of the DM1 cognitive profile [ 23 , 24 , 25 ] and have been proposed as prognostic factors of cognitive and structural brain progressive degeneration [ 19 , 26 ]. Moreover, subjects with DM1 frequently present psychiatric comorbidities embracing personality and/or mood disorders, and a characteristic emotional imbalance [ 27 , 28 ].…”

Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1

“…Significant silencing of target RNAs in the brain has also been achieved following intravenous coadministration of an oligonucleotide and angubindin-1 to increase the permeability of the BBB [ 133 ]. Older DM1 patients often manifest structural alterations of the brain related to disease duration such as ventricular dilation, cortical atrophy, and loss of grey volume [ 134 , 135 , 136 ]. Aberrant alternative splicing of MAPT is thought to lead to the accumulation of aggregated phosphorylated Tau and the formation of neurofibrillary tangles in the brains of DM1 patients [ 137 ].…”