Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia

Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2. Objectives: Our goal was to investigate the effects of genetic variants on risk and time to LID. Methods: We performed a genome-wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores (PRS) including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1612 PD patients with and 3175 without LID. Results: We found that GBA1 variants were associated with LID risk (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.21-2.26; P = 0.0017) and LRRK2 variants with reduced time to LID onset (hazard ratio [HR] = 1.42; 95% CI, 1.09-1.84; P = 0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (OR = 1.27; 95% CI, 1.03-1.56; P = 0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HR = 1.38; 95% CI, 1.07-1.79; P = 0.0128; HR = 1.38; 95% CI = 1.06-1.78; P = 0.0147). Conclusions: This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients

Effects of Combining Diaphragm Training with Electrical Stimulation on Balance, Pain, and Function in Athletes with Chronic Low Back Pain : A Randomized Clinical Trial

Abstract Background: It is unknown how diaphragm training combined with electrical stimulation affect balance, core stability, pain, and function in athletes with chronic low back pain (CLBP). This study aimed to explore the effects of combining diaphragm training with electrical stimulation on core stability, dynamic balance, pain, and function in young athletes with nonspecific CLBP.Methods: The design was a randomized clinical trial A total of 24 young adult athletes (12 women, 12 men) with non-specific CLBP were randomly allocated into experimental and control group. The experimental group received diaphragm training plus Transcutaneous Electrical Nerve Stimulation (TENS), while the control group received only TENS. Both groups underwent 12 sessions over a 4-week period. Static stability, dynamic balance, pain, and function were measured pre- and post-intervention.Results: Significant improvements in pain and function scores were found in both groups after completing the interventions. However, only the experimental group showed significant improvements in the static stability and dynamic balance post-intervention. The experimental group showed greater improvements in pain and static stability. No significant differences in function or dynamic balance were observed between the groups. Conclusions: The present study indicates that diaphragm training plus TENS can improve static stability, dynamic balance, function, and pain in young athletes with non-specific CLBP. It seems beneficial to add diaphragm training to rehabilitation programs for athletes with CLBP.Trial registration: The trial was retrospectively registered at the Iranian Registry of Clinical Trials on www.irct.ir (Identification number: IRCT20090228001719N8).</jats:p

Effects of combining diaphragm training with electrical stimulation on pain, function, and balance in athletes with chronic low back pain: a randomized clinical trial

Abstract Background It is unknown how diaphragm training combined with electrical stimulation affects pain, function, static stability, and balance in athletes with chronic low back pain (CLBP). This study aimed to explore the effects of combining diaphragm training with electrical stimulation on pain, function, static stability, and dynamic balance in athletes with nonspecific CLBP. Methods The design was a randomized clinical trial. A total of 24 amateur athletes (12 women, 12 men, mean age: 35.2 ± 9.8) with nonspecific CLBP were randomly allocated into two groups. The experimental group (n = 12) received diaphragm training plus Transcutaneous Electrical Nerve Stimulation (TENS), while the control group (n = 12) received TENS alone. Both groups underwent 12 sessions over a four-week period. Static stability, dynamic balance, pain, and function were measured pre- and post-intervention. Results Analysis of variance 2 × 2 revealed greater improvements in pain (p &lt; 0.001), static stability (p &lt; 0.001), and dynamic balance (p &lt; 0.01) in the experimental group compared to the control group. Function was improved in both groups following the interventions (p &lt; 0.001), and there was a trend of a larger improvement in the experimental group than the control group (p = 0.09). Fisher’s exact test showed that the experimental group reported ≥50% improvement only in the pain score, not function, compared to the group that received TENS alone (p = 0.005). Conclusions Pain, function, static stability, and dynamic balance were improved in both groups following 12 intervention sessions. However, pain, static stability, and dynamic balance were improved to a greater extent in diaphragm training plus TENS than TENS alone in amateur athletes with CLBP. Therefore, it seems beneficial to add diaphragm training to the rehabilitation program for athletes with nonspecific CLBP. Trial registration The trial was retrospectively registered in the Iranian Registry of Clinical Trials (www.irct.ir) on September 10, 2020 as IRCT20090228001719N8. </jats:sec

Effects of Combining Diaphragm Training With TENS&amp;nbsp;on Balance, Pain, and Function in Athletes With Chronic Low Back Pain: A Randomized Clinical Trial

Abstract Background: there is a lack of evidence about the effects of diaphragm training combined with TENS on balance, pain, and function in athletes with CLBP.Objectives: This study aimed to investigate the effects of combining diaphragm training with electrical stimulation on core stability, dynamic balance, pain, and function in young athletes with nonspecific CLBP.Design: Randomized clinical trialMethod: A total of 24 young adult athletes (12 women, 12 men) with non-specific CLBP were randomly allocated into experimental and control group. The experimental group received diaphragm training plus Transcutaneous Electrical Nerve Stimulation (TENS), while the control group received only TENS. Both groups underwent 12 sessions over a 4-week period. Static stability, dynamic balance, pain, and function were measured pre- and post-intervention.Results: Significant improvements in pain and function scores were found in both groups after completing the interventions. However, only the experimental group showed significant improvements in the static stability and dynamic balance post-intervention. The experimental group showed greater improvements in pain and static stability. No significant differences in function or dynamic balance were observed between the groups. Conclusions: The present study indicates that diaphragm training plus TENS can improve static stability, dynamic balance, function, and pain in young athletes with non-specific CLBP. It seems beneficial to add diaphragm training to rehabilitation programs for athletes with CLBP.The trial was retrospectively registered at the Iranian Registry of Clinical Trials on www.irct.ir (Identification number: IRCT20090228001719N8).</jats:p

Effects of combining diaphragm training with electrical stimulation on pain, function, and balance in athletes with chronic low back pain: a randomized clinical trial

Background: It is unknown how diaphragm training combined with electrical stimulation affects pain, function, static stability, and balance in athletes with chronic low back pain (CLBP). This study aimed to explore the effects of combining diaphragm training with electrical stimulation on pain, function, static stability, and dynamic balance in athletes with nonspecific CLBP. Methods: The design was a randomized clinical trial. A total of 24 amateur athletes (12 women, 12 men, mean age: 35.2 ± 9.8) with nonspecific CLBP were randomly allocated into two groups. The experimental group (n = 12) received diaphragm training plus Transcutaneous Electrical Nerve Stimulation (TENS), while the control group (n = 12) received TENS alone. Both groups underwent 12 sessions over a four-week period. Static stability, dynamic balance, pain, and function were measured pre- and post-intervention. Results: Analysis of variance 2 × 2 revealed greater improvements in pain (p < 0.001), static stability (p < 0.001), and dynamic balance (p < 0.01) in the experimental group compared to the control group. Function was improved in both groups following the interventions (p < 0.001), and there was a trend of a larger improvement in the experimental group than the control group (p = 0.09). Fisher’s exact test showed that the experimental group reported ≥50% improvement only in the pain score, not function, compared to the group that received TENS alone (p = 0.005). Conclusions: Pain, function, static stability, and dynamic balance were improved in both groups following 12 intervention sessions. However, pain, static stability, and dynamic balance were improved to a greater extent in diaphragm training plus TENS than TENS alone in amateur athletes with CLBP. Therefore, it seems beneficial to add diaphragm training to the rehabilitation program for athletes with nonspecific CLBP. Trial registration: The trial was retrospectively registered in the Iranian Registry of Clinical Trials (www.irct.ir) on September 10, 2020 as IRCT20090228001719N8. Keywords: Back pain, Diaphragm muscle, Breathing exercises, Transcutaneous electrical nerve stimulatio

Integrating digital gait data with metabolomics and clinical data to predict outcomes in Parkinson’s disease

Parkinson’s disease (PD) presents diverse symptoms and comorbidities, complicating its diagnosis and management. The primary objective of this cross-sectional, monocentric study was to assess digital gait sensor data’s utility for monitoring and diagnosis of motor and gait impairment in PD. As a secondary objective, for the more challenging tasks of detecting comorbidities, non-motor outcomes, and disease progression subgroups, we evaluated for the first time the integration of digital markers with metabolomics and clinical data. Using shoe-attached digital sensors, we collected gait measurements from 162 patients and 129 controls in a single visit. Machine learning models showed significant diagnostic power, with AUC scores of 83–92% for PD vs. control and up to 75% for motor severity classification. Integrating gait data with metabolomics and clinical data improved predictions for challenging-to-detect comorbidities such as hallucinations. Overall, this approach using digital biomarkers and multimodal data integration can assist in objective disease monitoring, diagnosis, and comorbidity detection

Education as Risk Factor of Mild Cognitive Impairment: The Link to the Gut Microbiome

peer reviewedBackground: With differences apparent in the gut microbiome in mild cognitive impairment (MCI) and dementia, and risk factors of dementia linked to alterations of the gut microbiome, the question remains if gut microbiome characteristics may mediate associations of education with MCI. Objectives: We sought to examine potential mediation of the association of education and MCI by gut microbiome diversity or composition. Design: Cross-sectional study. Setting: Luxembourg, the Greater Region (surrounding areas in Belgium, France, Germany). Participants: Control participants of the Luxembourg Parkinson’s Study. Measurements: Gut microbiome composition, ascertained with 16S rRNA gene amplicon sequencing. Differential abundance, assessed across education groups (0–10, 11–16, 16+ years of education). Alpha diversity (Chao1, Shannon and inverse Simpson indices). Mediation analysis with effect decomposition was conducted with education as exposure, MCI as outcome and gut microbiome metrics as mediators. Results: After exclusion of participants below 50, or with missing data, n=258 participants (n=58 MCI) were included (M [SD] Age=64.6 [8.3] years). Higher education (16+ years) was associated with MCI (Odds ratio natural direct effect=0.35 [95% CI 0.15–0.81]. Streptococcus and Lachnospiraceae-UCG-001 genera were more abundant in higher education. Conclusions: Education is associated with gut microbiome composition and MCI risk without clear evidence for mediation. However, our results suggest signatures of the gut microbiome that have been identified previously in AD and MCI to be reflected in lower education and suggest education as important covariate in microbiome studies.MCI-BIOME_20193. Good health and well-bein