Journal of Movement Disorders最新文献

Objective: Cognitive impairment is common in Parkinson's disease (PD), with few pharmacological options. We evaluated the effects of a digital cognitive training program (SUPERBRAIN), previously effective in Alzheimer's risk populations, on cognitive function in PD.

Methods: Twenty-nine patients with PD and mild cognitive impairment (PD-MCI) from four clinics were randomized to intervention (n=16) or control (n=7). The intervention group completed a 12-week, home-based, tablet cognitive training program (25-30 min/day, 7 days/week). Cognitive outcomes were assessed using the Seoul Neuropsychological Screening Battery pre- and post-intervention.

Results: Adherence was 79.4%. The intervention group showed significant improvements in the Seoul Verbal Learning Test (SVLT) delayed recall and controlled oral word association test, with no changes in controls. ANCOVA confirmed a greater SVLT improvement in the intervention group ((F-statistics = 7.15, P-value = 0.015, partial η² = 0.28).

Conclusions: SUPERBRAIN is feasible and improves cognitive function in PD-MCI.

Introduction: Studies outlining the genetic architecture of Parkinson's disease in India are sparse, and juvenile parkinsonism is underrepresented in the literature. The objective was to study the clinical, therapeutic, and genetic profile of patients with juvenile parkinsonism and to correlate phenotypic-genotypic characteristics.

Methods: This retrospective chart review was conducted in patients with suspected genetically mediated juvenile parkinsonism (onset≤21 years), who have undergone genetic testing at a tertiary care center in India from 2015-2024. The available phenotypic-genotypic characteristics were evaluated and compared between gene(+) and gene(-) patients.

Results: Forty patients (22 males, 55%) with juvenile parkinsonism were included with mean age at onset and presentation of 15.85±4.96 years and 26.37±10.11 years respectively. The mean duration of illness was 10.43±10.49 years. A positive family history was present in 40% and consanguinity in 45%. Bradykinesia was the most common motor symptom (95%) and cognitive impairment was the commonest non-motor symptom (17.5%). Pathogenic/likely pathogenic variants were identified in 27 patients (67.5 %), with variants in PRKN being the most common (n=8) followed by PLA2G6 (n=7). Gene(+) cases had significantly more severe disease with better levodopa response, more frequent familial consanguinity, oculomotor abnormality, motor fluctuations and dyskinesia. PARK-PLA2G6 patients had significantly more dystonia, gaze restriction, pyramidal signs, severe disease at presentation, with lesser LEDD and motor fluctuations compared to PARK-PRKN patients.

Conclusion: More than two-thirds (67.5%) of the juvenile parkinsonism patients in our cohort had an underlying monogenetic cause. PARK-PRKN, PARK-PLA2G6, and PARK-SYNJ1 are the common causes of genetically mediated juvenile parkinsonism in India.

Recent neuropathological and imaging studies support the concept of "brain-first vs. body-first" Parkinson's disease (PD), based on the α-Synuclein Origin site and Connectome model. The body-first phenotype is characterized by early involvement of the peripheral autonomic nervous system, particularly the cardiac sympathetic nerves and enteric nerves. ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) myocardial scintigraphy is a well-established method for evaluating cardiac sympathetic innervation. This review explores the potential of ¹²³I-MIBG scintigraphy as a biomarker to differentiate body-first phenotype from brain-first phenotype. Reduced ¹²³I-MIBG uptake has been observed in idiopathic REM sleep behavior disorder, pure autonomic failure, and incidental Lewy body disease-conditions strongly associated with prodromal or early-stage PD. Postmortem and biopsy evidence indicate α-synuclein accumulation in cardiac nerves and other peripheral sites, consistent with a bottom-up progression. α-Synuclein seed amplification assays further corroborate the association between peripheral α-synuclein burden and reduced ¹²³I-MIBG uptake. While ¹²³I-MIBG myocardial scintigraphy is a promising tool, its limitations include cost, limited availability, and potential confounding from underlying cardiac conditions. Nonetheless, early detection of cardiac sympathetic denervation via ¹²³I-MIBG imaging may enhance diagnosis, support subtype classification, and improve understanding of PD pathogenesis.