Characterization of the Pattern of Cognitive Impairment in Myotonic Dystrophy Type 1.

Background: Central nervous system involvement occurs in most patients with myotonic dystrophy type 1 (DM1): mental retardation characterizes congenital forms, while a mild cognitive impairment has been described in adult patients with classic DM1. Neuropathological studies documented neurofibrillary tangles and an aberrant tau-protein expression in brain tissues of patients and animal models of DM1. Objectives: To characterize the pattern of cognitive dysfunction occurring in DM1 and to analyze genotype-phenotype correlations in patients with DM1. Methods: We assessed the results of a detailed neuropsychological study, including Mini-Mental State Examination, memory, linguistic level, praxis, attentional and frontal-executive tasks, in a group of 70 patients with DM1, including 10 congenital and 60 classic forms. Statistical analysis of data was performed using analysis of variance for multiple tests. Results: Our study documented 2 distinct patterns of cognitive impairment in DM1: in particular, we confirmed the presence of a cognitive pattern characteristic of mental retardation in congenital cases, whereas in adult forms we documented an aging-related decline of frontal and temporal cognitive functions. No correlations were found between cognitive impairment and (CTG)(n) in leukocytes or severity of muscle involvement. Conclusions: Adult patients with DM1 frequently develop, with aging, a focal dementia: such findings agree with recent studies documenting an abnormal tau-protein expression in the brain tissues of patients with DM1. Cognitive decline may represent the only relevant clinical manifestation of DM1 in patients carrying very small (CTG)(n) expansions in leukocytes