Altered Impulsivity Across Drug-Naïve Parkinsonism, Isolated Rapid Eye Movement Sleep Behavior Disorder, and Their High-Risk Relatives.

OBJECTIVE: To determine multidimensional impulsivity levels across different early stages of α-synucleinopathy. METHODS: This cross-sectional study investigated motor and decisional impulsivity levels using a panel of computerized tasks among drug-naïve parkinsonism patients, isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) patients and their first-degree relatives (iRBD-FDRs), and control participants. Trait impulsivity and impulse control behaviors were assessed by self-reported questionnaires. RESULTS: A total of 27 drug-naïve parkinsonism patients, 157 iRBD patients, 66 iRBD-FDRs, and 82 control participants were recruited. Parkinsonism and iRBD patients had fewer numbers of extracted beads in beads task 1 and 2 (both p < 0.001), and a higher rate of irrational choice in task 1 (p = 0.046) before making decisions, and fewer numbers of pumps of unexploded blue balloons in the balloon analog risk task (p = 0.004) than control participants, indicating a higher level of reflection impulsivity and a lower level of risk taking, respectively. iRBD patients had more no-go errors in the go/no-go task than control participants (padjusted = 0.036), suggesting a higher level of motor impulsivity. iRBD-FDRs with dream-enactment behaviors had fewer numbers of extracted beads (p = 0.047) in beads task 2 than FDRs without dream-enactment behaviors, suggesting a possible higher level of reflection impulsivity. INTERPRETATION: A complex construct of altered impulsivity with decreased risk taking, but increased reflection and motor impulsivity, has already occurred at the prodromal and early stages of α-synucleinopathy, which have implications for underlying pathophysiology and clinical management of α-synucleinopathy, especially for impulse control behaviors upon dopaminergic drug treatment. ANN NEUROL 2024;95:544-557.

Objective and subjective sleep in patients with non-seasonal major depressive disorder and eveningness - Results from a randomized controlled trial of bright light therapy.

STUDY OBJECTIVES: This study examines the (dis)agreement between objective and subjective sleep and their prospective changes in a randomized controlled trial of bright light therapy (BLT) in patients with major depressive disorder (MDD) and eveningness. METHODS: A total of 93 adults were randomized to receive either 30-min daily of 10,000 lux BLT or 50lux placebo dim red light therapy (DRL group) for a total of 5 weeks. Actigraphic data were collected at the baseline and during the last week of treatment. (Dis)Concordance of diary and actigraphic sleep parameters were assessed by partial correlations and Bland-Altman plots, and the associations between these discrepancies to depression severity was assessed by linear regression models. Changes of sleep parameters were assessed by linear mixed models. RESULTS: Significant correlations were found between subjective sleep timings and chronotype to actigraphic parameters. Discrepancies between diary- and actigraphic-measures were observed, and patients with more severe depressive symptoms were associated with a greater under-estimation of total sleep time (TST). A greater advance in the diary-based time to fall sleep and rise time were achieved in the BLT group as compared to the DRL group, while diary-based wake after sleep onset (WASO), TST and sleep efficiency (SE) comparably improved with time in both groups. There was no significant difference between the two groups in the actigraphic parameters after treatment. CONCLUSIONS: In this study, we found that depression severity influenced subjective report of sleep. BLT led to a greater advance in subjective sleep timings when compared to the placebo group.

Early- and late-onset of isolated rapid eye movement sleep behavior disorder: A retrospective cohort study.

OBJECTIVE: Age at onset of neurodegenerative disease has significant implications in differentiating disease profiles. We aimed to determine whether age at onset could identify clinical and neurodegenerative profiles in patients with isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) - a prodromal stage of α-synucleinopathies. METHODS: In this retrospective cohort study, the time of the first episode of dream-enactment behaviors that the patient/bed-partners recalled at the time of the patient's first visit to sleep clinic was collected. The distribution of age at onset was examined and patients were dichotomized into early- and late-onset groups based on the intersection point of underlying two Gaussian distributions of onset age. RESULTS: A total of 241 patients were included. The intersection of underlying two Gaussian models of onset age was 64.6 years, yielding 168 early- (median onset age: 58.0 years, range: 38.0-64.0) and 73 late-onset patients (median onset age: 70.0 years, range: 65.0-82.0). Among them, 154 of early- and 68 late-onset patients were followed-up. Late-onset patients had milder RBD symptoms, but worse sleep, cognition, olfactory and motor functions, and a higher risk of phenoconversion (adjusted hazard ratio (aHR) = 2.2, 95% confidence interval (CI) = 1.2-3.9), especially to probable dementia with Lewy bodies (DLB) (aHR = 8.9, 95% CI = 3.0-26.2), than early-onset patients. CONCLUSIONS: Late-onset iRBD was associated with a higher level of neurodegenerative markers and a quicker phenoconversion, especially to probable DLB. Age at onset of iRBD could help identify clinical features and predict prognosis of iRBD.

Large-scale network dysfunction in α-Synucleinopathy: A meta-analysis of resting-state functional connectivity.

BACKGROUND: Although dysfunction of large-scale brain networks has been frequently demonstrated in patients with α-Synucleinopathy (α-Syn, i.e., Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy), a consistent pattern of dysfunction remains unclear. We aim to investigate network dysfunction in patients with α-Syn through a meta-analysis. METHODS: Whole-brain seed-based resting-state functional connectivity studies (published before September 1st, 2020 in English) comparing α-Syn patients with healthy controls (HC) were retrieved from electronic databases (PubMed, Web of Science, and EMBASE). Seeds from each study were categorized into networks by their location within a priori functional networks. Seed-based effect size mapping with Permutation of Subject Images analysis of between-group effects identified the network systems in which α-Syn was associated with hyperconnectivity (increased connectivity in α-Syn vs. HC) or hypoconnectivity (decreased connectivity in α-Syn vs. HC) within and between each seed-network. This study was registered on PROSPERO (CRD42020210133). FINDINGS: In total, 136 seed-based voxel-wise resting-state functional connectivity datasets from 72 publications (3093 α-Syn patients and 3331 HC) were included in the meta-analysis. We found that α-Syn patients demonstrated imbalanced connectivity among subcortical network, cerebellum, and frontal parietal networks that involved in motor functioning and executive control. The patient group was associated with hypoconnectivity in default mode network and ventral attention network that involved in cognition and attention. Additionally, the patient group exhibited hyperconnectivity between neural systems involved in top-down emotion regulation and hypoconnectivity between networks involved in bottom-up emotion processing. INTERPRETATION: These findings supported neurocognitive models in which network dysfunction is tightly linked to motor, cognitive and psychiatric symptoms observed in α-Syn patients. FUNDING: This study was partially supported by the Research Grants Council of Hong Kong (Grant No. RGC14116121).

Adjunctive bright light treatment with gradual advance in unipolar major depressive disorder with evening chronotype - A randomized controlled trial.

BACKGROUND: Unipolar non-seasonal depressed patients with concomitant evening chronotype were associated with poor clinical outcomes and higher non-remission rate. This study aims to examine the efficacy of adjunctive bright light therapy with gradual timing advance in a randomized, assessor and prescriber-blinded controlled trial. METHOD: Participants were randomly allocated to receive 5 weeks of either bright white light therapy (BLT) or dim red light (DRL) with the same advancement protocol. Participants were followed up till 5 months after treatment. Primary outcomes included (i) remission rate and (ii) the severity of depression. The analysis was conducted using Kaplan-Meier survival analysis, Cox proportional hazard analysis and linear mixed models. RESULTS: A total of 93 participants (46.4 ± 11.7 years old, 80% female) were randomized. The cumulative remission rate for the BLT and the DRL groups was 67.4% and 46.7%, respectively. Time to remission was shorter for the BLT group relative to the DRL group (log-rank test p = 0.024). Cox proportional hazard survival analysis showed that patients in the BLT group had a higher probability of achieving remission relative to patients in the DRL group [hazard ratio = 1.9 (95% CI = 1.1- 3.4), p = 0.026]. Further sensitivity analysis demonstrated greater improvement in 17-Hamilton Depression Score (group × time interaction, p = 0.04) in the BLT group for those who were adherent to light therapy. CONCLUSIONS: The use of bright light therapy with gradual advance protocol is an effective adjunctive treatment resulting in quicker and a higher rate of remission of depression in patients with non-seasonal unipolar depression and evening-chronotype.

An evaluation of the mental health impact of SARS-CoV-2 on patients, general public and healthcare professionals: A systematic review and meta-analysis.

BACKGROUND: The global impact of COVID-19 pandemic continues to affect the lives of billions of people with recurrent waves. Healthcare systems are struggling to manage pre-existing patient care and recurring covid-19 demands. As a result, we evaluated the mental health impact using systematic review and meta-analysis. METHODS: A comprehensive search was undertaken from April 2020 to 22nd January 2021 using multiple electronic databases. A systematic review protocol was developed and published on PROSPERO registration; CRD42020181481. A random-effects model was used to compute pooled estimates of anxiety, depression, PTSD, insomnia and suicidal thoughts. FINDINGS: Our search yielded 11,295 studies and of those 287 met the inclusion criteria. The meta-analysis of 206 studies revealed minimal differences in prevalence of anxiety, depression, and PTSD among HCPs compared with the public during the pandemic but higher prevalence of suicidal thoughts/ideation or self-harm (11% vs 5.8%) and lower prevalence of wellbeing (28.2% vs 52.6%) among the public compared to HCPs. INTERPRETATION: The pandemic has led to a high mental health burden especially amongst HCPs and higher suicidal ideation and lower wellbeing in general public which warrants further investigation and management globally. These findings highlight an emerging critical public health issue that requires urgent solutions.