Cognitive Decline and White Matter Integrity Degradation in Myotonic Dystrophy Type I

Abstract

BACKGROUND AND PURPOSE Myotonic Dystrophy Type I (DM1) is a neurodegenerative, genetic, and multisystemic disorder with a large variety of symptoms due to a CTG trinucleotide expansion located on Dystrophia Myotonica Protein Kinase (DMPK) gene. Previous reports have shown cognitive deterioration in these patients. Given that white matter (WM) degradation has also been reported in DM1 patients, here we explored if alterations in the cognitive profile of DM1 patients could be related to the deterioration of WM. METHODS A total of 22 classic DM1 patients with age range (18‐56 years) and 22 matched healthy control subjects were neuropsychological evaluated by the Cambridge Neuropsychological Test Automated (CANTAB). Patients were evaluated with the Muscular Impairment Rating Scale (MIRS). We then evaluated the cerebral WM integrity using the Fractional Anisotropy (FA) index obtained from the Diffusion Tensor Imaging (DTI) data acquired with a 3T MR scanner. RESULTS DM1 patients showed generalized reduction of WM integrity across the brain. Similarly, patients’ neuropsychological evaluation showed significant deficits in memory and problem‐solving tasks. Correlation analyses showed a significant correlation between FA deterioration at frontal, temporomedial, and parietal lobes and delayed matched to sample deficits. CONCLUSIONS Our results suggest that despite the pervasive WM integrity loss in DM1 disorder, specific memory impairments can be associated to discreet areas of WM deterioration in these patients.

Cognitive Deficits, Apathy, and Hypersomnolence Represent the Core Brain Symptoms of Adult-Onset Myotonic Dystrophy Type 1

“…However, in the context of understanding the neurobiology of DM1 and moving toward reliable therapeutic targets, it is vital to be able to identify which symptoms are related to brain pathology and which ones are secondary to the stress of dealing with a chronic disease and not due to underlying brain pathology (15). Previous studies have shown significant relationships between neuroimaging findings and cognitive impairments, including white matter track DTI measures, ventricular enlargement, gray matter and white matter atrophy, white matter lesions, increased hippocampal volume, and FDG-PET frontotemporal hypometabolism (4,9,12,19,(66)(67)(68). Previous studies have also confirmed cognitive decline over time with age and a negative association with disease duration (49,50,69,70).…”

“…Previous studies have shown significant relationships between neuroimaging findings and cognitive impairments, including white matter track DTI measures, ventricular enlargement, gray matter and white matter atrophy, white matter lesions, increased hippocampal volume, and FDG-PET frontotemporal hypometabolism ( 4 , 9 , 12 , 19 , 66 – 68 ). Previous studies have also confirmed cognitive decline over time with age and a negative association with disease duration ( 49 , 50 , 69 , 70 ).…”

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

“…WM lesions (WML) and WM hyperintensities (WMH) have also been reported, as well as cortical volume loss and corpus callosum atrophy 17 , 18 . In addition, WM tractography studies 18 , 19 have shown significant diffusivity alterations, including an increase in mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and a decrease in fractional anisotropy (FA). The multiple alterations found in WM have prompted some authors to state that DM1 is a predominantly white matter disease 9 .…”

Increased functional connectivity of white-matter in myotonic dystrophy type 1

“…Neuroimaging studies revealed widespread abnormalities in the brain structure of DM1 patients, particularly white-matter damage ( Minnerop et al, 2011 ; Caso et al, 2014 ; Wozniak et al, 2014 ; Baldanzi et al, 2016 ; Gourdon and Meola, 2017 ). The abnormalities of white-matter in DM1 patients manifested have increased white-matter hyperintensity load, decreased microstructural integrity, and significant diffusivity alterations ( Cabada et al, 2017 ; Lopez-Titla et al, 2021 ). These white-matter abnormalities in DM1 patients may be associated with episodic memory, executive function, and visuo-spatial impairments, which impact the quality of their life ( Meola et al, 1996 ; Modoni et al, 2008 ; Rakocevic-Stojanovic et al, 2014 ; Gallais et al, 2015 ; Schneider-Gold et al, 2015 ; Baldanzi et al, 2016 ; Okkersen et al, 2017 ).…”