A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease.

BACKGROUND: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD). OBJECTIVE: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). METHODS: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. RESULTS: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. CONCLUSIONS: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. TRIAL REGISTRATION: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 - Sept 13, 2022.

Transcutaneous spinal direct current stimulation improves locomotor learning in healthy humans.

BACKGROUND: Ambulation is an essential aspect of daily living and is often impaired after brain and spinal cord injuries. Despite the implementation of standard neurorehabilitative care, locomotor recovery is often incomplete. OBJECTIVE: In this randomized, sham-controlled, double-blind, parallel design study, we aimed to determine if anodal transcutaneous spinal direct current stimulation (anodal tsDCS) could improve training effects on locomotion compared to sham (sham tsDCS) in healthy subjects. METHODS: 43 participants underwent a single backwards locomotion training (BLT) session on a reverse treadmill with concurrent anodal (n = 22) or sham (n = 21) tsDCS. The primary outcome measure was speed gain measured 24 h post-training. We hypothesized that anodal tsDCS + BLT would improve training effects on backward locomotor speed compared to sham tsDCS + BLT. A subset of participants (n = 31) returned for two additional training days of either anodal (n = 16) or sham (n = 15) tsDCS and underwent (n = 29) H-reflex testing immediately before, immediately after, and 30 min post-training over three consecutive days. RESULTS: A single session of anodal tsDCS + BLT elicited greater speed gain at 24 h relative to sham tsDCS + BLT (p = 0.008, two-sample t-test, adjusted for one interim analysis after the initial 12 subjects). Anodal tsDCS + BLT resulted in higher retention of the acquired skill at day 30 relative to sham tsDCS + BLT (p = 0.002) in the absence of significant group differences in online or offline learning over the three training days (p = 0.467 and p = 0.131). BLT resulted in transient down-regulation of H-reflex amplitude (Hmax/Mmax) in both test groups (p < 0.0001). However, the concurrent application of anodal-tsDCS with BLT elicited a longer lasting effect than sham-tsDCS + BLT (p = 0.050). CONCLUSION: tsDCS improved locomotor skill acquisition and retention in healthy subjects and prolonged the physiological exercise-mediated downregulation of excitability of the alpha motoneuron pool. These results suggest that this strategy is worth exploring in neurorehabilitation of locomotor function.

The effect of mindfulness meditation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.

There is a growing interest in the effectiveness of mindfulness meditation for sleep disturbed populations. Our study sought to evaluate the effect of mindfulness meditation interventions on sleep quality. To assess for relative efficacy, comparator groups were restricted to specific active controls (such as evidenced-based sleep treatments) and nonspecific active controls (such as time/attention-matched interventions to control for placebo effects), which were analyzed separately. From 3303 total records, 18 trials with 1654 participants were included. We determined the strength of evidence using four domains (risk of bias, directness of outcome measures, consistency of results, and precision of results). At posttreatment and follow-up, there was low strength of evidence that mindfulness meditation interventions had no effect on sleep quality compared with specific active controls (ES 0.03 (95% CI -0.43 to 0.49)) and (ES -0.14 (95% CI -0.62 to 0.34)), respectively. Additionally, there was moderate strength of evidence that mindfulness meditation interventions significantly improved sleep quality compared with nonspecific active controls at postintervention (ES 0.33 (95% CI 0.17-0.48)) and at follow-up (ES 0.54 (95% CI 0.24-0.84)). These preliminary findings suggest that mindfulness meditation may be effective in treating some aspects of sleep disturbance. Further research is warranted.