Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder.

BACKGROUND: Reduced cortical acetylcholinesterase activity, as measured by 11 C-donepezil positron emission tomography (PET), has been reported in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD). However, its progression and clinical implications have not been fully investigated. Here, we explored the relationship between longitudinal changes in brain acetylcholinesterase activity and cognitive function in iRBD. METHODS: Twelve iRBD patients underwent 11 C-donepezil PET at baseline and after 3 years. PET images were interrogated with statistical parametric mapping (SPM) and a regions of interest (ROI) approach. Clinical progression was assessed with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III). Cognitive function was rated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). RESULTS: From baseline to follow-up, the mean 11 C-donepezil distribution volume ratio (DVR) decreased in the cortex (p = 0.006), thalamus (p = 0.013), and caudate (p = 0.013) ROI. Despite no significant changes in the group mean MMSE or MoCA scores being observed, individually, seven patients showed a decline in their scores on these cognitive tests. Subgroup analysis showed that only the subgroup of patients with a decline in cognitive scores had a significant reduction in mean cortical 11 C-donepezil DVR. CONCLUSIONS: Our results show that severity of brain cholinergic dysfunction in iRBD patients increases significantly over 3 years, and those changes are more severe in those with a decline in cognitive test scores.

Prevalence and severity of freezing of gait in a Danish cohort of people with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a widespread neurodegenerative disorder characterised by wide range of symptoms. Freezing of gait (FoG), a transient feeling that the patient's feet are nailed to the floor, resulting in an inability to move, is a particularly distressful symptom. The assessment of FoG can be challenging. Often, clinicians are reliant on patients' subjective experiences and patient questionnaires such as the Freezing of Gait Questionnaire (FOGQ) and its updated version, the New FOGQ (NFOGQ).Until now, the NFOGQ has not been validated and piloted for use in Danish. Therefore, few attempts have been made to assess the prevalence and severity of FoG in Danish patients with PD. METHODS: This report describes a two-step process of adapting the NFOGQ into Danish and piloting its use among a cohort of patients with PD. A satisfactory translation (Danish NFOGQ) was produced and successfully piloted. RESULTS: The translation showed robust test-retest reliability after two weeks. Patients fully understood the questionnaire. Using the Danish NFOGQ in an online prevalence survey, we found that 35.7% of respondents had experienced FoG and that the prevalence correlated with disease duration. CONCLUSION: The Danish NFOGQ appears to be appropriate for assessing FoG in Danish patients with PD in both clinical and research settings. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Neuroinflammation and Immune Changes in Prodromal Parkinson's Disease and Other Synucleinopathies.

Multiple lines of clinical and pre-clinical research support a pathogenic role for neuroinflammation and peripheral immune system dysfunction in Parkinson's disease. In this paper, we have reviewed and summarised the published literature reporting evidence of neuroinflammation and peripheral immune changes in cohorts of patients with isolated REM sleep behaviour disorder and non-manifesting carriers of GBA or LRRK2 gene mutations, who have increased risk for Parkinsonism and synucleinopathies, and could be in the prodromal stage of these conditions. Taken together, the findings of these studies suggest that the early stages of pathology in Parkinsonism involve activation of both the central and peripheral immune systems with significant crosstalk. We consider these findings with respect to those found in patients with clinical Parkinson's disease and discuss their possible pathological roles. Moreover, those factors possibly associated with the immune response, such as the immunomodulatory role of the affected neurotransmitters and the changes in the gut-brain axis, are also considered.