Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis.

BACKGROUND: Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear. OBJECTIVES: To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs). SEARCH METHODS: An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. A third author was involved in case of disagreements. We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements. Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach. MAIN RESULTS: We included 154 RCTs with a total of 7837 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 60 (2721 participants), and 48 (3029 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results. We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson's Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39). Severity of motor signs The evidence from the NMA (60 studies; 2721 participants) suggests that dance and gait/balance/functional training probably have a moderate beneficial effect on the severity of motor signs (dance: mean difference (MD) -10.18, 95% confidence interval (CI) -14.87 to -5.36; gait/balance/functional training: MD -7.50, 95% CI -11.39 to -3.48; moderate confidence), and multi-domain training probably has a small beneficial effect on the severity of motor signs (MD -5.90, 95% CI -9.11 to -2.68; moderate confidence). The evidence also suggests that endurance, aqua-based, strength/resistance, and mind-body training might have a small beneficial effect on the severity of motor signs (endurance training: MD -5.76, 95% CI -9.78 to -1.74; aqua-based training: MD -5.09, 95% CI -10.45 to 0.40; strength/resistance training: MD -4.96, 95% CI -9.51 to -0.40; mind-body training: MD -3.62, 95% CI -7.24 to 0.00; low confidence). The evidence is very uncertain about the effects of "Lee Silverman Voice training BIG" (LSVT BIG) and flexibility training on the severity of motor signs (LSVT BIG: MD -6.70, 95% CI -16.48 to 3.08; flexibility training: MD 4.20, 95% CI -1.61 to 9.92; very low confidence). Quality of life The evidence from the NMA (48 studies; 3029 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -15.15, 95% CI -23.43 to -6.87; moderate confidence). The evidence also suggests that mind-body, gait/balance/functional, and multi-domain training and dance might have a small beneficial effect on QoL (mind-body training: MD -7.22, 95% CI -13.57 to -0.70; gait/balance/functional training: MD -6.17, 95% CI -10.75 to -1.59; multi-domain training: MD -5.29, 95% CI -9.51 to -1.06; dance: MD -3.88, 95% CI -10.92 to 3.00; low confidence). The evidence is very uncertain about the effects of gaming, strength/resistance, endurance, and flexibility training on QoL (gaming: MD -8.99, 95% CI -23.43 to 5.46; strength/resistance training: MD -6.70, 95% CI -12.86 to -0.35; endurance training: MD -6.52, 95% CI -13.74 to 0.88; flexibility training: MD 1.94, 95% CI -10.40 to 14.27; very low confidence). Adverse events Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we observed little evidence of differences between exercise types. AUTHORS' CONCLUSIONS: We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.

Can Physical Exercise Be Considered as a Promising Enhancer of Global Cognition in People with Parkinson's Disease? Results of a Systematic Review and Meta-Analysis.

Background: Physical exercise interventions are known to improve quality of life, motor and non-motor symptoms in people with Parkinson's disease (PD). However, systematic reviews and meta-analyses on cognitive outcomes are rare. Objective: To perform a systematic review and meta-analysis of physical exercise intervention effects compared with passive and active control groups (CGs) on global cognition in people with PD. Methods: A literature search was performed for randomized controlled trials (RCTs) on physical exercise interventions in PD using nine databases. We included RCTs reporting global cognition outcomes. A meta-analysis was performed using random-effects models and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Bias was assessed with the revised Cochrane Risk of Bias tool and the certainty of evidence was rated using the GRADE approach. Results: Seventeen studies (ten with passive, seven with active CGs) were included in the systematic review. Exercise interventions varied considerably between studies. The meta-analysis included nine studies with 236 people with PD (seven with passive, two with active CGs). The SMD was 0.33 (95% CI 0.00; 0.65) demonstrating a small effect (p = 0.05) in favor of physical exercise. Compared with passive CGs, physical exercise had a small non-significant effect (SMD = 0.22, 95% CI -0.14;0.58, p = 0.24). Compared with active CGs, physical exercise had a medium significant effect (SMD = 0.72, 95% CI 0.12;1.33, p = 0.02). Conclusions: Physical exercise may increase global cognition in people with PD, but the evidence is very uncertain. Further large-scale RCTs are needed to confirm this finding and to identify the most effective type of physical exercise for improving cognition.

Experiences of fatigued persons with multiple sclerosis with multimodal agility-based exercise training and the ReFEx study protocol: a qualitative extension of a feasibility study.

OBJECTIVES: (1) To explore experiences of fatigued persons with multiple sclerosis (pwMS) with a new multimodal agility-based exercise training (MAT) framework and (2) to investigate the demands of the Rehabilitation, Fatigue, and Exercise (ReFEx) study protocol, which compares high-frequency MAT and 'traditional' strength and endurance training (SET) to identify possible adaptations for a powered randomised controlled trial (RCT). DESIGN: A qualitative interview study nested within a feasibility RCT, comparing MAT and SET. SETTING: Neurological inpatient rehabilitation centre in Germany. PARTICIPANTS: Twenty-two pwMS were recruited for the feasibility study. Six were selected from MAT and SET, respectively, for semistructured face-to-face interviews prior to discharge, following a purposive sampling strategy. Participants had low physical disability but were at least moderately fatigued. INTERVENTIONS: During inpatient rehabilitation (4-6 weeks) MAT participants attended group-based and manual-based MAT sessions in the gym (5×/week, 30 min) and the pool (3×/week, 30 min). SET participants exercised individually on a cycle ergometer (5×/week, 22 min) and on strength training machines (3×/week, 30 min). RESULTS: Three key categories emerged from the interviews: (1) facilitators regarding MAT were variety and playfulness, group setting and challenging exercises. Barriers regarding MAT were feeling overburdened, feeling pressured in the group setting and the wish to perform 'traditional' strength training (not part of MAT). (2) MAT benefits were of physical and psychological nature, with improved balance stated the most. (3) Demands described the perceived exertion during MAT and SET, reflecting that there is no accumulation of fatigue during the intervention. CONCLUSIONS: MAT is appreciated by pwMS and includes facilitators less attainable with 'traditional' SET. Evaluation of MAT in a powered RCT is indicated, if rest breaks postsession, and screening for negative self-evaluation and social comparison are considered. Future (qualitative) research should investigate the important factors of inpatient rehabilitation contributing to fatigue reduction in pwMS. TRIAL REGISTRATION NUMBER: DRKS00023943; German Clinical Trials Register.

Cost-Effectiveness Analyses of Non-Pharmacological and Non-Surgical Interventions in Idiopathic Parkinson's Disease: A Systematic Review.

Background: Interest in non-pharmacological/non-surgical interventions to treat Parkinson's disease (PD) has substantially increased. Although a few health-economic studies have been conducted, summary information on the cost-effectiveness is still scarce. Objective: To give an overview of cost-effectiveness analyses (CEA) focusing on non-pharmacological/non-surgical interventions in PD patients. Methods: A systematic literature search was conducted in five databases. Studies were included that provided cost-effectiveness analysis (CEA) or cost-utility analysis (CUA) of non-pharmacological/non-surgical interventions in PD patients. Study quality was assessed with the Drummond and CHEERS 2022 checklists respectively, for economic evaluation. Results: N = 9 studies published between 2012-2023 were identified. Most studies undertook a CUA (n = 5); n = 3 reported a combination of CEA and CUA, and n = 1 a pure CEA. Most studies (n = 6) examined physical exercise. The CEA studies identified additional costs of 170€ -660€  for the improvement of one single unit of a clinical outcome and savings of 18.40€ -22.80€  per score gained as measured with established instruments. The four studies that found significant quality of life benefits show large variations in the incremental cost effectiveness ratio (ICER) of 3,220€ -214,226€  per quality-adjusted life year (QALY); notably interventions were heterogenous regarding content and intensity. Conclusions: Despite increasing numbers of non-pharmacological/non-surgical intervention trials in PD patients, health-economic evaluations are rare. The examined intervention types and health-economic results vary greatly. Together with the heterogeneity of the health-economic studies these factors limit the conclusions that can be drawn. Further research and a standardization of methods is needed to allow decision makers to make meaningful interpretations, and to allocate scarce resources.

"There is only one motive fun." Perspectives of participants and providers of physical exercise for people with Parkinson's disease.

PURPOSE: To explore the perspectives of people with Parkinson's disease (PD) and exercise providers regarding facilitating factors, barriers, needs, and demands relating to physical exercise for people with PD. MATERIALS AND METHODS: Focus group discussions or telephone interviews of 30 people with PD (with or without an active sports history) and 13 providers were conducted and analyzed using structuring content analysis. RESULTS: Factors facilitating participation in physical exercise included motivation-enhancing elements (enjoyment, group training environment) and providers with sufficient qualifications in PD-specific training demands. Identified barriers were lack of motivation, physical limitations, poor service accessibility, and inadequate matching of intervention groups based on capability or age. Providers found it difficult to design and conduct group trainings for people with PD with varying physical limitations. Having an active sports history before PD-onset was described as generally beneficial, though a competitive mindset could lead to frustration. People with PD reported needing their physicians to provide better education regarding physical exercise. CONCLUSION: Enjoyment of physical exercise is a key aspect of maintaining physical activity engagement, which should be considered more in research and clinical practice. Developing qualifications for providers could help to broaden and enhance the dissemination of PD-specific exercise approaches. Physicians should be trained to encourage physical exercise.Implications for rehabilitationPhysicians should highlight the benefits and be knowledgeable regarding the availability of physical exercise interventions for people with PD.Additional physical exercise providers should become qualified to work with people with PD.The joyfulness of physical exercise interventions is a key aspect of maintaining physical activity engagement for people with PD.

Higher Risk of Many Physical Health Conditions in Sexual Minority Men: Comprehensive Systematic Review and Meta-Analysis in Gay- and Bisexual-Identified Compared with Heterosexual-Identified Men.

Purpose: The purpose of this study was to provide a systematic review and, where possible, meta-analysis on the prevalence of physical health conditions in sexual minority men (SMM, i.e., gay- and bisexual-identified men) compared with heterosexual-identified men. Methods: A systematic literature search in the databases MEDLINE, Embase, CENTRAL, CINAHL, and Web of Science was conducted on epidemiological studies on physical health conditions, classified in the Global Burden of Disease project and published between 2000 and 2021. Meta-analyses comparing odds ratios were calculated. Results: In total, 23,649 abstracts were screened, and 32 studies were included in the systematic review. Main findings were that (1) Largest differences in prevalence by sexual identity were found for chronic respiratory diseases, particularly asthma: overall, SMM were significantly almost 50% more likely to suffer from asthma than heterosexual men. (2) Evidence of higher prevalence was also found for chronic kidney diseases and headache disorders in gay men and for hepatitis B/C in both gay and bisexual men. (3) We found an overall trend that bisexual men were more affected by some of the physical health conditions compared with gay men (e.g., cardiovascular diseases, asthma). However, regarding cancer, headache disorders, and hepatitis, gay men were more affected. Conclusion: We found evidence of physical health disparities by sexual identity, suggesting more health issues in SMM. Since some of these findings rely on few comparisons or small samples of SMM only, this review is intended to be a vehement plea for routinely including sexual identity assessment in health research and clinical practice.

Comprehensive systematic review and meta-analysis on physical health conditions in lesbian- and bisexual-identified women compared with heterosexual-identified women.

BACKGROUND: Sexual minority individuals experience discrimination, leading to mental health disparities. Physical health disparities have not been examined to the same extent in systematic reviews so far. OBJECTIVES: To provide a systematic review and, where possible, meta-analyses on the prevalence of physical health conditions in sexual minority women (i.e. lesbian- and bisexual-identified women) compared to heterosexual-identified women. DESIGN: The study design is a systematic review with meta-analyses. DATA SOURCES AND METHODS: A systematic literature search in MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science databases was conducted on epidemiologic studies on physical health conditions, classified in the Global Burden of Disease project, published between 2000 and 2021. Meta-analyses pooling odds ratios were calculated. RESULTS: In total, 23,649 abstracts were screened and 44 studies were included in the systematic review. Meta-analyses were run for arthritis, asthma, back pain, cancer, chronic kidney diseases, diabetes, headache disorders, heart attacks, hepatitis, hypertension, and stroke. Most significant differences in prevalence by sexual identity were found for chronic respiratory conditions, especially asthma. Overall, sexual minority women were significantly 1.5-2 times more likely to have asthma than heterosexual women. Furthermore, evidence of higher prevalence in sexual minority compared to heterosexual women was found for back pain, headaches/migraines, hepatitis B/C, periodontitis, urinary tract infections, and acne. In contrast, bisexual women had lower cancer rates. Overall, sexual minority women had lower odds of heart attacks, diabetes, and hypertension than heterosexual women (in terms of diabetes and hypertension possibly due to non-consideration of pregnancy-related conditions). CONCLUSION: We found evidence for physical health disparities by sexual identity. Since some of these findings rely on few comparisons only, this review emphasizes the need for routinely including sexual identity assessment in health research and clinical practice. Providing a more detailed picture of the prevalence of physical health conditions in sexual minority women may ultimately contribute to reducing health disparities.

Multimodal agility-based exercise training (MAT) versus strength and endurance training (SET) to improve multiple sclerosis-related fatigue and fatigability during inpatient rehabilitation: a randomized controlled pilot and feasibility study [ReFEx].

BACKGROUND: Multimodal agility-based exercise training (MAT) is a group-based exercise training framework for persons with multiple sclerosis (pwMS) with a potential to impact fatigue and fatigability. In a mixed-methods design, this study evaluated the feasibility of implementing MAT in an inpatient rehabilitation setting and the feasibility of a randomized controlled trial (RCT) study protocol with 'traditional' strength and endurance training (SET) as an active control condition. Secondarily, preliminary outcome data was acquired. METHODS: PwMS with low to moderate disability and self-reported fatigue were randomly allocated to either MAT or SET when starting inpatient rehabilitation (4-6 weeks). The MAT-participants exercised in a group following a MAT-manual (sessions were gym- (5x/week) and pool-based (3x/week)). SET-participants exercised individually 5x/week on a cycle ergometer, and 3x/week on strength training machines. Feasibility assessments focused on processes, resources, management, time, and scientific domains. Assessed clinical outcomes at admission and discharge included perceived fatigue, motor and cognitive fatigability, cognitive performance, motor function, and balance confidence. Perceived fatigue was reassessed 1, 4, and 12 weeks after discharge. Feasibility was determined regarding predetermined progression criteria. RESULTS: Twenty-two participants were randomized. Both groups performed the minimum number of sessions (> 18), and retention was adequate (73-91%). SET-participants performed more sessions than MAT-participants (30.8 vs. 22.7) and stayed longer in the facility (34.2 vs. 31.6 days). Non-eligibility of admitted pwMS was high (74% non-eligible), mainly due to high EDSS and inability to attend pool-based sessions. Consequently, recruitment (1.8/month) was slower than the predetermined progression criterium. Baseline assessments took longer than required (only 50% completed within 3 days). Short-term fatigue reduction was similar for both groups. Motor fatigability also improved in both groups, whereas cognitive fatigability deteriorated. In MAT, average improvement in walking endurance (43.9 m) exceeded minimal important change values for individuals (> 26.9 m). CONCLUSIONS: Progressing to a definitive RCT necessitates adaptation of eligibility criteria. In the present design it will also be difficult to attain similar dosing of interventions. A multicenter RCT focused only on gym-based MAT might be another option to assess the effect of MAT. The primary outcome measure should be able to measure change in perceived fatigue more robustly. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00023943, date of registration: 23 September 2021.

Training cognition in older male prisoners: lessons learned from a feasibility study.

With increasing numbers of older prisoners, effective strategies for preventing and treating age-associated diseases, such as cognitive disorders, are needed. As pharmacological therapies are limited, non-pharmacological interventions are increasingly recognized as potential treatment strategies. One approach is cognitive training (CT). However, no study has investigated CT in the prison setting. Thus, this one-arm feasibility trial aims to analyze the feasibility of (i) the study protocol and (ii) the implementation of multimodal CT for older prisoners. Eighteen older male prisoners from two specific divisions for older prisoner participated in 12 weekly CT sessions using the NEUROvitalis program. The feasibility analysis included recruitment, dropout, and CT participation rates, and motivation for and satisfaction with CT (using 6-point Likert-scales). The study protocol demonstrated sufficient feasibility with high recruitment rates between 46 and 50%. Therefore, the CT implementation was successful: Only one prisoner ceased participation; all others completed the CT sessions (i.e., attended > 75% of the sessions). Prisoners reported high CT motivation and satisfaction, and would recommend CT. This is the first study to demonstrate CT feasibility in older prisoners. Although more research is needed, these results are a starting point for expanding services to include cognitively enhancing activities for older prisoners.This one-arm feasibility study was pre-registered in the German Clinical Trials Register (DRKS; ID: DRKS00020227).), Registered 11 Mai 2021 https://drks.de/search/de/trial/DRKS00020227 .

Improved connectivity and cognition due to cognitive stimulation in Alzheimer's disease.

Background: Due to the increasing prevalence of Alzheimer's disease (AD) and the limited efficacy of pharmacological treatment, the interest in non-pharmacological interventions, e.g., cognitive stimulation therapy (CST), to improve cognitive dysfunction and the quality of life of AD patients are on a steady rise. Objectives: Here, we examined the efficacy of a CST program specifically conceptualized for AD dementia patients and the neural mechanisms underlying cognitive or behavioral benefits of CST. Methods: Using neuropsychological tests and MRI-based measurements of functional connectivity, we examined the (neuro-) psychological status and network changes at two time points: pre vs. post-stimulation (8 to 12 weeks) in the intervention group (n = 15) who received the CST versus a no-intervention control group (n = 15). Results: After CST, we observed significant improvement in the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale, cognitive subsection (ADAS-cog), and the behavioral and psychological symptoms of dementia (BPSD) scores. These cognitive improvements were associated with an up-regulated functional connectivity between the left posterior hippocampus and the trunk of the left postcentral gyrus. Conclusion: Our data indicate that CST seems to induce short-term global cognition and behavior improvements in mild to moderate AD dementia and enhances resting-state functional connectivity in learning- and memory-associated brain regions. These convergent results prove that even in mild to moderate dementia AD, neuroplasticity can be harnessed to alleviate cognitive impairment with CST.

Resting state EEG as biomarker of cognitive training and physical activity's joint effect in Parkinson's patients with mild cognitive impairment.

BACKGROUND: Cognitive decline is a major factor for the deterioration of the quality of life in patients suffering from Parkinson's disease (PD). Recently, it was reported that cognitive training (CT) in PD patients with mild cognitive impairment (PD-MCI) led to an increase of physical activity (PA) accompanied by improved executive function (EF). Moreover, PA has been shown to alter positively brain function and cognitive abilities in PD. Both observations suggest an interaction between CT and PA. OBJECTIVES: A previous multicenter (MC) study was slightly significant when considering independent effects of interventions (CT and PA) on EF. Here, we use MC constituent single center data that showed no effect of interventions on EF. Thus, this exploratory study considers pooling data from both interventions to gain insight into a recently reported interaction between CT and PA and provide a proof of principle for the usefulness of resting state EEG as a neurophysiological biomarker of joint intervention's effect on EF and attention in PD-MCI. METHODS: Pre- and post-intervention resting state EEG and neuropsychological scores (EF and attention) were obtained from 19 PD-MCI patients (10 (CT) and 9 (PA)). We focused our EEG analysis on frontal cortical areas due to their relevance on cognitive function. RESULTS: We found a significant joint effect of interventions on EF and a trend on attention, as well as trends for the negative correlation between attention and theta power (pre), the positive correlation between EF and alpha power (post) and a significant negative relationship between attention and theta power over time (post-pre). CONCLUSIONS: Our results support the role of theta and alpha power at frontal areas as a biomarker for the therapeutic joint effect of interventions.

Classification Of MeMory InTerventions: Rationale and developmental process of the COMMIT tool.

ABSTRACTOver the last decades, numerous memory interventions have been developed to mitigate memory decline in normal ageing. However, there is a large variability in the success of memory interventions, and it remains poorly understood which memory intervention programs are most effective and for whom. This is partially explained by the heterogeneity of memory intervention protocols across studies as well as often poor reporting of the study design. To facilitate a reporting framework that enables researchers to systemize the content and design of memory intervention paradigms, we developed the Classification Of MeMory InTerventions (COMMIT) tool using a 3-stage developmental process. Briefly, COMMIT was based on qualitative content analysis of already existing memory intervention studies published between April 1983 and July 2020, and iteratively validated by both internal and external expert panels. COMMIT provides an easily-applicable interactive tool that enables systematic description of memory intervention studies, together with instructions on how to use this classification tool. Our main goal is to provide a tool that enables the reporting and classification of memory interventions in a transparent, comprehensible, and complete manner, to ensure a better comparability between memory interventions, and, to ultimately contribute to the question which memory intervention shows the greatest benefits.

Physical Exercise as a Potential Treatment for Fatigue in Parkinson's Disease? A Systematic Review and Meta-Analysis of Pharmacological and Non-Pharmacological Interventions.

BACKGROUND: Fatigue is one of the most common and debilitating non-motor symptoms among patients with Parkinson's disease (PD) and significantly impacts quality of life. Therefore, effective treatment options are needed. OBJECTIVE: To provide an update on randomized controlled trials (RCTs) including pharmacological and non-pharmacological (but non-surgical) treatments that examine the effects of fatigue on PD patients. METHODS: We searched the MEDLINE, EMBASE, PsycINFO, CENTRAL, and CINAHL databases for (cross-over) RCTs on pharmacological and non-pharmacological interventions for treating fatigue in PD patients until May 2021. Meta-analyses for random-effects models were calculated when two or more studies on the same treatment option were available using standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: Fourteen pharmacological and 16 non-pharmacological intervention RCTs were identified. For pharmacological approaches, a meta-analysis could only be performed for modafinil compared to placebo (n = 2) revealing a non-significant effect on fatigue (SMD = - 0.21, 95% CI - 0.74-0.31, p = 0.43). Regarding non-pharmacological approaches, physical exercise (n = 8) following different training approaches versus passive or placebo control groups showed a small significant effect (SMD = - 0.37, 95% CI - 0.69- - 0.05, p = 0.02) which could not be demonstrated for acupuncture vs. sham-acupuncture (SMD = 0.16, 95% CI - 0.19-0.50, p = 0.37). CONCLUSION: Physical exercise may be a promising strategy to treat fatigue in PD patients. Further research is required to examine the efficacy of this treatment strategy and further interventions. Future studies should differentiate treatment effects on physical and mental fatigue as the different underlying mechanisms of these symptoms may lead to different treatment responses. More effort is required to develop, evaluate, and implement holistic fatigue management strategies for PD patients.

A systematic review on prognostic factors and models for changes in quality of life and depressive symptoms after multi-domain cognitive training in healthy older adults: Who benefits?

BACKGROUND: As we age, cognitive abilities decline which can lead to a decrease in quality of life (QoL) and an increase in depressive symptoms even in healthy (i.e., non-clinical) older adults. Cognitive trainings (CT) are a promising approach to not only improve cognition, but also QoL and mood. However, it is unclear which prognostic factors are associated with changes in QoL and depression after CT. OBJECTIVE: To identify prognostic factors and models of changes in QoL and depressive symptoms after a multi-domain CT in healthy older adults. METHODS: MEDLINE, Web of Science Core Collection, CENTRAL and PsycInfo were systematically searched for multi-domain CT studies in healthy older adults until August 2022. Studies investigating prognostic factors and/or models on QoL and depressive symptoms were included. Risk of bias was assessed using the QUIPS and the PROBAST tool. RESULTS: Our search revealed N = 12,916 studies, of which only 6 could be included in the review. Prognostic factors included were sociodemographics, cognitive reserve, cognitive baseline level, and cognitive change. However, data were too rare and heterogenous regarding the assessment measures of QoL and depressive scores, the used multi-domain CT and the investigated prognostic factors to draw clear conclusions or conduct meta-analyses. CONCLUSION: There is an urgent need for research on prognostic factors and models of changes in QoL and depressive symptoms after CT in healthy older participants as they could help to tailor interventions to individuals in terms of future precision medicine approaches.

Effects of motor-cognitive training on dual-task performance in people with Parkinson's disease: a systematic review and meta-analysis.

Motor-cognitive training in Parkinson's disease (PD) can positively affect gait and balance, but whether motor-cognitive (dual-task) performance improves is unknown. This meta-analysis, therefore, aimed to establish the current evidence on the effects of motor-cognitive training on dual-task performance in PD. Systematic searches were conducted in five databases and 11 studies with a total of 597 people (mean age: 68.9 years; mean PD duration: 6.8 years) were included. We found a mean difference in dual-task gait speed (0.12 m/s (95% CI 0.08, 0.17)), dual-task cadence (2.91 steps/min (95% CI 0.08, 5.73)), dual-task stride length (10.12 cm (95% CI 4.86, 15.38)) and dual-task cost on gait speed (- 8.75% (95% CI - 14.57, - 2.92)) in favor of motor-cognitive training compared to controls. The GRADE analysis revealed that the findings were based on high certainty evidence. Thus, we can for the first time systematically show that people with PD can improve their dual-task ability through motor-cognitive training.

Multidomain cognitive training increases physical activity in people with Parkinson's disease with mild cognitive impairment.

INTRODUCTION: Cognitive impairment in Parkinson's disease (PD), especially in patients with mild cognitive impairment (PD-MCI), coincides with less physical activity. Cognitive trainings (CT) have been found to promote laboratory environment-based movement. Knowledge about their effect in natural home-based environment, reflecting everyday function, is sparse. This explorative study investigated short-term effects of CT on physical activity assessed by home-based accelerometry, and its relation to change of cognitive function over time and non-cognitive outcomes in patients with PD-MCI. Cognitive and non-cognitive correlates of movement parameters at pretest were evaluated as well. METHODS: Eighteen patients with PD-MCI of the TrainParC study were analyzed. Those patients received either a 6-week multidomain group CT or physical training (PT). Physical activity and sedentary behavior were assessed with wearable accelerometers worn up to seven days pre- and post-training. RESULTS: Patients in the CT group displayed significantly greater increases in active periods after training than patients assigned to PT. In the CT group, increases in executive functioning were associated with increases in active periods and decreases in active mean bout length after training. At pretest, reduced working memory correlated with longer sedentary mean bout length, and impairment in activities of daily living (ADL) correlated with a higher number of sedentary periods. CONCLUSION: Study data revealed that CT can increase physical activity in patients with PD-MCI, possibly due to effects on executive functions, which needs further investigation in larger sample sizes. Lower working memory performance and ADL impairment might be associated with a more inactive lifestyle in patients with PD-MCI.

Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis.

BACKGROUND: Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear. OBJECTIVES: To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs). SEARCH METHODS: An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. A third author was involved in case of disagreements.  We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements. Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach. MAIN RESULTS: We included 156 RCTs with a total of 7939 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 71 (3196 participants), and 55 (3283 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results. We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39). Severity of motor signs The evidence from the NMA (71 studies; 3196 participants) suggests that dance has a moderate beneficial effect on the severity of motor signs (mean difference (MD) -10.32, 95% confidence interval (CI) -15.54 to -4.96; high confidence), and aqua-based, gait/balance/functional, and multi-domain training might have a moderate beneficial effect on the severity of motor signs (aqua-based: MD -7.77, 95% CI -13.27 to -2.28; gait/balance/functional: MD -7.37, 95% CI -11.39 to -3.35; multi-domain: MD -6.97, 95% CI -10.32 to -3.62; low confidence). The evidence also suggests that mind-body training and endurance training might have a small beneficial effect on the severity of motor signs (mind-body: MD -6.57, 95% CI -10.18 to -2.81; endurance: MD -6.43, 95% CI -10.72 to -2.28; low confidence). Flexibility training might have a trivial or no effect on the severity of motor signs (MD 2.01, 95% CI -4.82 to 8.98; low confidence). The evidence is very uncertain about the effects of strength/resistance training and "Lee Silverman Voice training BIG" (LSVT BIG) on the severity of motor signs (strength/resistance: MD -6.97, 95% CI -11.93 to -2.01; LSVT BIG: MD -5.49, 95% CI -14.74 to 3.62; very low confidence). Quality of life The evidence from the NMA (55 studies; 3283 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -14.98, 95% CI -23.26 to -6.52; moderate confidence). The evidence also suggests that endurance training might have a moderate beneficial effect, and that gait/balance/functional and multi-domain training might have a small beneficial effect on QoL (endurance: MD -9.16, 95% CI -15.68 to -2.82; gait/balance/functional: MD -5.64, 95% CI -10.04 to -1.23; multi-domain: MD -5.29, 95% CI -9.34 to -1.06; low confidence). The evidence is very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on QoL (mind-body: MD -8.81, 95% CI -14.62 to -3.00; gaming: MD -7.05, 95% CI -18.50 to 4.41; strength/resistance: MD -6.34, 95% CI -12.33 to -0.35; dance: MD -4.05, 95% CI -11.28 to 3.00; LSVT BIG: MD 2.29, 95% CI -16.03 to 20.44; flexibility: MD 1.23, 95% CI -11.45 to 13.92; very low confidence). Adverse events Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we observed little evidence of differences between exercise types. AUTHORS' CONCLUSIONS: We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.

Cognitive training for older prisoners: a qualitative analysis of prisoners' and staff members' perceptions.

Introduction: Correctional institutions are challenged by increasing numbers of older prisoners. Existing literature highlights the vulnerability of this group that is reflected by various somatic and mental health issues including cognitive dysfunctions. Although cognitive training studies in various target groups of older people have been conducted, there is lack of data regarding cognitive training in older prisoners. A structured cognitive group training program ("NEUROvitalis Prison") with 12 weekly sessions was offered to male prisoners in Germany. Methods: Post intervention an exploratory qualitative study was conducted. Prisoners (N = 18) and staff (N = 4) perspectives were explored by conducting face-to-face semi-structured interviews. Audiotaped data were fully transcribed and deductive-inductive content analyses applied. Results: Both the prisoners and the staff perceived the cognitive training as very positive and stimulating. Moreover, the importance of the training was pronounced in terms of an increase in self-esteem and understanding of cognition and aging in the prisoners. Discussion: Our data indicate that cognitive training may be a feasible and valuable intervention for older prisoners that will be appreciated by both inmates and staff. The qualitative data provide substantial insight into the experiences with the applied cognitive training program. Moreover, valuable modifications for future conduct can be derived.

Randomised controlled pilot and feasibility study of multimodal agility-based exercise training (MAT) versus strength and endurance training (SET) to improve multiple sclerosis-related fatigue and fatigability during inpatient rehabilitation (ReFEx): study protocol.

INTRODUCTION: Subjective fatigue and objectively assessed fatigability are common symptoms in persons with multiple sclerosis (pwMS). Recent work has suggested a positive effect of balance and motor control training (BMCT) in reducing fatigue. It is unclear whether this effect can also be attained during inpatient rehabilitation. Multimodal agility-based exercise training (MAT) has been developed as a framework that incorporates BMCT with added agility components but has not been applied to pwMS. Therefore, this study will evaluate the feasibility of a randomised controlled trial comparing MAT against strength and endurance training (SET) for the improvement of MS-related fatigue and fatigability in a German neurological rehabilitation centre. METHODS AND ANALYSIS: A total of 24 pwMS (Expanded Disability Status Scale ≤5.0, Fatigue Scale for Motor and Cognitive Functions ≥53) will be randomly assigned to either SET or land and water-based MAT for 4-6 weeks during inpatient rehabilitation. Assessments of subjective fatigue, motor and cognitive fatigability, cognitive and cardiorespiratory performance, and balance confidence will be performed at admission and discharge. Subjective fatigue will also be assessed at 1, 4 and 12 weeks after discharge. Feasibility outcomes will include patients' acceptance of study procedures and interventions, recruitment rate, retention rate, time needed to complete baseline assessments, intervention adherence and fidelity. All quantitative outcomes will be reported descriptively. A total of 12 pwMS (6 per group) will be interviewed to gain insights into participants' experiences during study participation. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of the University of Bonn (reference number: 543/20). Dissemination of findings is planned via peer-reviewed journals, conferences and media releases. TRIAL REGISTRATION NUMBER: DRKS00023943.