Age‐related cognitive decline in myotonic dystrophy type 1: An 11‐year longitudinal follow‐up study

Abstract

Background Myotonic dystrophy type 1 (DM1) is an inherited multi‐systemic disease involving the central nervous system (CNS) and is consequently characterized by a range of cognitive impairments. However, whether this cognitive profile progresses over time is still a matter of debate. The aim of this study was to longitudinally assess a DM1 sample, in order to compare, for the first time, this progression with that of a control group. Clinical and socio‐demographic predictive factors potentially implicated in this possible decline are analysed. Method Seventy‐five DM1 patients with childhood, juvenile, adult, and late‐onset, and 54 control participants were re‐assessed in an 11‐year follow‐up with a comprehensive neuropsychological battery. The analyses employed were mixed ANOVA for repeated measures to test intergroup comparisons over time and multiple linear regression for predictive variable analysis. Results Myotonic dystrophy type 1 patients significantly worsened in visuospatial/visuoconstructive abilities and visual memory compared with controls. Multiple linear regression revealed that progression of cognitive impairment measured by copy of the Rey–Osterrieth complex figure was predicted by muscular impairment, whilst on the block design test age predicted the change with a cut‐off at 31 years of age. Discussion A domain‐specific progressive cognitive decline was found in DM1, with visuospatial/visuoconstructive abilities showing the greatest vulnerability to the passage of time. In addition to important clinical implications, these results suggest the need for the scientific community to delve deeper into the potential mechanisms underlying early cognitive decline in this population.

Neurodegeneration trajectory in pediatric and adult/late DM1: A follow‐up MRI study across a decade

“…1 Furthermore, from a neuropsychological perspective, recent findings suggest that cognitive functions suffer a decline in several areas, beyond that expected in normal aging. [2][3][4][5][6] Although neuroimaging data are thought to support the previously suggested hypothesis of neurodegenerative processes in DM1, to the best of our knowledge, there have been only two previous attempts to longitudinally study a hypothesized progressive impairment in brain structures. While Gliem et al 7 did not find a greater volume loss over time in DM1 for either gray or white matter tissue, Conforti et al found a progression in white matter lesions along with greater brain atrophy assessed by the ventricular/brain ratio.…”

“…CNS studies with a focus on brain pathology have defined DM1 as a combination of tauopathy, spliceopathy, and RNAopathy, all of which contribute to neurodegeneration 1 . Furthermore, from a neuropsychological perspective, recent findings suggest that cognitive functions suffer a decline in several areas, beyond that expected in normal aging 2–6 …”

Targeting Myotonic Dystrophy Type 1 with Metformin

“…In particular, congenital and childhood-onset DM1 patients suffer mental retardation, whereas patients with the adult-onset forms may show varying degrees of cognitive dysfunction, where a positive correlation between triplet expansion length and patients’ age is observed. Nowadays, there are data supporting an age-dependent progressive cognitive decline in DM1 patients [ 35 ], that correlates with brain atrophy [ 36 ].…”

Brief assessment of cognitive function in myotonic dystrophy: Multicenter longitudinal study using computer‐assisted evaluation

“…The 12‐year study of 16 DM1 patients did not show significant longitudinal changes 35 . In a much larger longitudinal study comparing DM1 participants and controls, significant changes occurred after 11 years, but only on measures that assessed visual‐spatial/construction abilities and visual memory, 6 whereas performance on measures of attention, reaction time, verbal abilities, verbal memory, and executive functioning did not change significantly. In fact, the only significant change over time in our study was apparent improvement of executive function from baseline to 3 months, as determined by the GMLT, which suggested a learning or practice effect.…”