Short communication: Lifetime musical activity and resting-state functional connectivity in cognitive networks.

BACKGROUND: Participation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear. OBJECTIVE: This cross-sectional study investigated the association between lifetime musical activity and resting-state functional connectivity (RSFC) in three higher-order brain networks: the Default Mode, Fronto-Parietal, and Salience networks. METHODS: We assessed 130 cognitively unimpaired participants (≥ 60 years) from the baseline cohort of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Lifetime musical activity was operationalized by the self-reported participation in musical instrument playing across early, middle, and late life stages using the Lifetime of Experiences Questionnaire (LEQ). Participants who reported musical activity during all life stages (n = 65) were compared to controls who were matched on demographic and reserve characteristics (including education, intelligence, socioeconomic status, self-reported physical activity, age, and sex) and never played a musical instrument (n = 65) in local (seed-to-voxel) and global (within-network and between-network) RSFC patterns using pre-specified network seeds. RESULTS: Older participants with lifetime musical activity showed significantly higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal as well as frontal regions, namely the right temporal pole and the right precentral gyrus extending into the superior frontal gyrus, compared to matched controls. There were no significant group differences in global RSFC within or between the three networks. CONCLUSION: We show that playing a musical instrument during life relates to higher RSFC of the medial prefrontal cortex with distant brain regions involved in higher-order cognitive and motor processes. Preserved or enhanced functional connectivity could potentially contribute to better brain health and resilience in OA with a history in musical activity. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00007966, 04/05/2015).

Gender Differences in Task Specific Dystonia: What Can we Learn from Musician's Dystonia?

BACKGROUND: Musician's Dystonia (MD) is a task specific, focal dystonia which usually occurs only at the instrument. The pathophysiology is not fully understood, but several risk factors like over-practice and genetic predisposition are known. Interestingly, 80% of those affected are men, which stands in contrast to the gender distribution in other focal dystonias, such as cervical dystonia. OBJECTIVES: Our aim was to evaluate the difference in women and men with regard to risk factors leading to MD. METHODS: We investigated known risk factors for MD in a large cohort of 364 MD patients by retrospectively collecting data on practice behavior and family history. RESULTS: In line with previous studies, we found a ratio of ~4:1 men to women. Age at onset of MD was significantly lower in women; however, subsequent analysis revealed that it was a positive family history (FH+) and not gender that was associated with a lower age at onset. Furthermore, we found that those with negative family history had accumulated more practice time until onset of MD. CONCLUSIONS: These results imply that the earlier age at onset in women did not depend on gender but was due to the higher proportion of a positive family history. In contrast, men were less likely to have a positive family history, suggesting that genetic factors may not be the primary reason for the higher prevalence of MD in men. Instead, differences in practice behaviors between men and women may contribute to this gender disparity.

The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis.

BACKGROUND: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients' safety and management. OBJECTIVES: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients. METHODS: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®. RESULTS: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue. CONCLUSIONS: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients.

The comorbidity and co-medication profile of patients with progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. OBJECTIVES: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. METHODS: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®. RESULTS: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions. CONCLUSIONS: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients.

Practice behaviors as trigger factor for the onset of Musicians' Dystonia.

Musician's Dystonia (MD) is a task-specific movement disorder that results in an involuntary cramping of muscles involved in playing an instrument such as the upper limbs or the embouchure. It is usually painless and occurs in general only at the instrument. The pathophysiology of MD is not completely understood. The present study aimed at assessing differences in practice behaviors between pianists affected by MD and Healthy Controls (HC) in the years preceding the onset of the disease. Thus, we investigated to what extent practice quantity can be considered a trigger of Musicians' Dystonia. The results showed that despite comparable practice behaviors in childhood, MD pianists incremented the amount of daily practice to a greater extent than their healthy colleagues, especially in the second and in the third decade of life. Thus, subsequent logistic regression analysis showed that high amounts of daily practice might significantly increase the risk of developing MD. Furthermore, gender-related differences in practice behaviors across groups were identified, indicating that male pianists from the MD group might not have practiced significantly more than HC male pianists before the onset of the disease. To the authors' knowledge, these are the first empirical evidence of the role of dysfunctional practice behaviors in triggering MD, which has clinical and educational implications.

Embouchure Dystonia as a Network Disease.

While the pathophysiology of embouchure dystonia, a sub-entity of musician's dystonia, is still not fully understood, recent research has shown that it involves alterations of several brain functions and networks. Maladaptive plasticity in sensorimotor integration, sensory perception, and deficient inhibitory mechanisms at cortical, subcortical, and spinal level seem to contribute to its pathophysiology. Furthermore, functional systems of the basal ganglia and the cerebellum are involved, clearly pointing toward a network disorder. We therefore propose a novel network model, based on electrophysiological and recent neuroimaging studies highlighting embouchure dystonia.