RESUMO
Background: In spinocerebellar ataxia type 3 (SCA3), volume loss has been reported in the basal ganglia, an iron-rich brain region, but iron content has not been examined. Recent studies have reported that patients with SCA6 have markedly decreased iron content in the cerebellar dentate, coupled with severe volume loss. Changing brain iron levels can disrupt cognitive and motor functions, yet this has not been examined in the SCAs, a disease in which iron-rich regions are affected. Methods: In the present study, we used quantitative susceptibility mapping (QSM) to measure tissue magnetic susceptibility (indicating iron concentration), structural volume, and normalized susceptibility mass (indicating iron content) in the cerebellar dentate and basal ganglia in people with SCA3 (n = 10) and SCA6 (n = 6) and healthy controls (n = 9). Data were acquired using a 7T Philips MRI scanner. Supplemental measures assessed motor, cognitive, and mood domains. Results: Putamen volume was lower in both SCA groups relative to controls, replicating prior findings. Dentate susceptibility mass and volume in SCA6 was lower than in SCA3 or controls, also replicating prior findings. The novel finding was that higher basal ganglia susceptibility mass in SCA6 correlated with lower cognitive performance and greater motor impairment, an association that was not observed in SCA3. Cerebellar dentate susceptibility mass, however, had the opposite relationship with cognition and motor function in SCA6, suggesting that, as dentate iron is depleted, it relocated to the basal ganglia, which contributed to cognitive and motor decline. By contrast, basal ganglia volume loss, rather than iron content, appeared to drive changes in motor function in SCA3. Conclusion: The associations of higher basal ganglia iron with lower motor and cognitive function in SCA6 but not in SCA3 suggest the potential for using brain iron deposition profiles beyond the cerebellar dentate to assess disease states within the cerebellar ataxias. Moreover, the role of the basal ganglia deserves greater attention as a contributor to pathologic and phenotypic changes associated with SCA.
RESUMO
Many Parkinson's disease (PD) patients notice that motor symptoms worsen during stress, and experience stress-related neuropsychiatric symptoms such as anxiety and depression. Here we investigated which personal and disease characteristics are associated with perceived stress in PD, which PD symptoms are sensitive to stress, and we assessed self-reported benefits of stress-reducing strategies such as mindfulness. We sent an online survey to the Fox Insight cohort (n = 28,385 PD patients, n = 11,413 healthy controls). The survey included specific questions about the influence of stress on PD symptoms, use of stress-reducing strategies, and several validated scales measuring perceived stress, anxiety, dispositional mindfulness, rumination, and self-compassion. We received completed surveys from 5000 PD patients and 1292 controls. Patients perceived more stress than controls. Among patients, stress was correlated with increased rumination (R = 0.65), lower quality of life (R = -0.56), lower self-compassion (R = -0.65), and lower dispositional mindfulness (R = -0.48). Furthermore, patients indicated that stress significantly worsened both motor symptoms - especially tremor - and non-motor symptoms. Physical exercise was most frequently used to reduce stress (83.1%). Mindfulness was practiced by 38.7% of PD respondents, who noticed improvement in both motor and non-motor symptoms. Among non-users, 43.4% were interested in gaining mindfulness skills. We conclude that PD patients experience greater levels of stress than controls, and that stress worsens both motor and non-motor symptoms. Mindfulness may improve PD symptom severity, with the strongest effects on anxiety and depressed mood. These findings justify further controlled studies to establish the merits of mindfulness and other stress-alleviating interventions.