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Radboud University, 30 oktober 2023, Promotores : Engelen, B.G.M. van, Knoop, H. Co-promotor : Raaphorst, J., Contains fulltext : 296449.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 220138.pdf (Publisher’s version ) (Closed access), Objective: In the autosomal dominant, multisystem, chronic progressive disease myotonic dystrophy type 1 (DM1), cognitive deficits may originate from disrupted functional brain networks. We aimed to use network analysis of resting-state electro-encephalography (EEG) recordings of patients with DM1 and matched unaffected controls to investigate changes in network organization in large-scale functional brain networks and correlations with cognitive deficits. Methods: In this cross-sectional study, 28 adult patients with genetically confirmed DM1 and 26 age-, sex- and education-matched unaffected controls underwent resting-state EEG and neuropsychological assessment. We calculated the Phase Lag Index (PLI) to determine EEG frequency-dependent functional connectivity between brain regions. Functional brain networks were characterized by applying concepts from graph theory and compared between-groups. Network topology was evaluated using the minimum spanning tree (MST). We evaluated correlations between network metrics and neuropsychological tests that showed statistically significant between-group differences. Results: Functional connectivity estimated as whole-brain median PLI for DM1 patients versus healthy controls was higher in theta band (0.141 [0.050] versus 0.125 [0.018], p = 0.029), and lower in the upper alpha band (0.154 [0.048] versus 0.182 [0.073], p = 0.038), respectively. Functional MST-constructed networks in DM1 patients were significantly dissimilar from healthy controls in the delta, (p = 0.009); theta, (p = 0.009); lower alpha, (p = 0.036); and upper alpha, (p = 0.008) bands. In evaluation of local MST network measures, trends toward networks with higher global integration in the theta band and lower global integration in the upper alpha band were observed. Compared to unaffected controls, DM1 patients performed worse on tests of attention, motor function, executive function and visuospatial memory. Visuospatial memory correlated with the global media

Contains fulltext : 201926.pdf (publisher's version ) (Open Access), The myriad of neuropsychiatric manifestations reported in myotonic dystrophy type 1 may have its origin in alterations of complex brain network interactions at the structural level. In this study, we tested the hypothesis that altered white matter microstructural integrity and network organisation were present in a cohort of individuals with DM1 compared to unaffected controls, which was expected to be associated with CNS related disease manifestations of DM1. We performed a cross-sectional neuropsychological assessment and brain MRI in 25 myotonic dystrophy type 1 (DM1) patients and 26 age, sex and educational level matched unaffected controls. Patients were recruited from the Dutch cohort of the OPTIMISTIC study, a concluded trial which had included ambulant, genetically confirmed DM1 patients who were severely fatigued. We applied graph theoretical analysis on structural networks derived from diffusion tensor imaging (DTI) data and deterministic tractography to determine global and local network properties and performed group-wise comparisons. Furthermore, we analysed the following variables from structural MRI imaging: semi-quantitative white matter hyperintensity load andwhite matter tract integrity using tract-based spatial statistics (TBSS). Structural white matter networks in DM1 were characterised by reduced global efficiency, local efficiency and strength, while the network density was compatible to controls. Other findings included increased white matter hyperintensity load, and diffuse alterations of white matter microstructure in projection, association and commissural fibres. DTI and network measures were associated (partial correlations coefficients ranging from 0.46 to 0.55) with attention (d2 Test), motor skill (Purdue Pegboard test) and visual-constructional ability and memory (copy subtest of the Rey-Osterrieth Complex Figure Test). DTI and network measures were not associated with clinical measures of fatigue (checklist individual strength, fatig

Contains fulltext : 201714.pdf (publisher's version ) (Closed access), Background: To gain insight into the prevalence of apathy, depression and anxiety symptoms in myotonic dystrophy type 1 (DM1) patients on the basis of a systematic review with a meta-analysis. Methods: One author systematically searched and selected studies from Embase, Medline, PsychInfo and Web of Science (index periods up to August 2018). Data extraction and bias assessment were performed independently by two authors. We calculated (1) a weighted pooled prevalence and (2) weighted pooled standardized mean difference (Hedges' g) from studies comparing DM1 patients to healthy and/or neuromuscular disease controls separately for symptoms of depression, anxiety and apathy. Results: The pooled prevalences of depression (26 studies, n = 1267 DM1 patients), anxiety (19 studies, n = 896) and apathy (5 studies, n = 428), were 18% (95%CI: 12-25), 16 (95%CI: 13-18) and 55% (95%CI: 55-60), respectively. Effect sizes (Hedges’ g) for depression, anxiety and apathy in DM1 patients compared to healthy controls were 1.04 (95%-CI: 0.71 to 1.37), 0.87 (95%-CI: 0.51 to 1.24) and 1.13 (95%-CI:0.54-1.71). Effect sizes for symptoms of depression, anxiety and apathy were 0.29 (95% CI: -0.12 to 0.70), 0.45 (95%-CI: -0.31 to 1.22) and 1.12 (95%-CI: 0.32-1.93) for DM1 patients versus neuromuscular disease controls. In most analyses, statistical heterogeneity was high. Conclusions: Estimated pooled prevalences of clinically significant levels of symptoms of depression, anxiety and apathy in DM1 are 19, 17 and 55% respectively. Symptoms of depression and anxiety in DM1 may reflect reactive adjustment to progressive impairment and restricted participation similar to other chronic neuromuscular disease. The literature on the prevalence and severity of apathy, although a clinically relevant and characteristic symptom of DM1, is relatively scarce.

Contains fulltext : 177996.pdf (publisher's version ) (Closed access), To examine the cognitive profile of patients with myotonic dystrophy type 1 (DM1) on the basis of a systematic review and meta-analysis of the literature. Embase, Medline and PsycInfo were searched for studies reporting >= 1 neuropsychological test in both DM1 patients and healthy controls. Search, data extraction and risk of bias analysis were independently performed by two authors to minimize error. Neuropsychological tests were categorized into 12 cognitive domains and effect sizes (Hedges' g) were calculated for each domain and for tests administered in >= 5 studies. DM1 participants demonstrated a significantly worse performance compared to controls in all cognitive domains. Effect sizes ranged from -.33 (small) for verbal memory to -1.01 (large) for visuospatial perception. Except for the domains global cognition, intelligence and social cognition, wide confidence intervals (CIs) were associated with moderate to marked statistical heterogeneity that necessitates careful interpretation of results. Out of the individual tests, the Rey-Osterrieth complex figure-copy (both non-verbal memory and visuoconstruction) showed consistent impairment with acceptable heterogeneity. In DM1 patients, cognitive deficits may include a variable combination of global cognitive impairment with involvement across different domains, including social cognition, memory and visuospatial functioning. Although DM1 is a heterogeneous disorder, our study shows that meta-analysis is feasible, contributes to the understanding of brain involvement and may direct bedside testing. The protocol for this study has been registered in PROSPERO (International prospective register of systematic reviews) under ID: 42016037415.