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

Abstract

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 onDystrophia 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. 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. 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. 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.