Effects and Mechanisms of Exercise on Brain-Derived Neurotrophic Factor (BDNF) Levels and Clinical Outcomes in People with Parkinson's Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson's disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors. METHOD: A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson's disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included. RESULTS: A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I2 = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as "good" in three trials, "fair" in one trial, and "poor" in one trial. CONCLUSION: Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF.

Delivering Multidisciplinary Rehabilitation Care in Parkinson's Disease: An International Consensus Statement.

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative disorder impacting everyday function and quality of life. Rehabilitation plays a crucial role in improving symptoms, function, and quality of life and reducing disability, particularly given the lack of disease-modifying agents and limitations of medications and surgical therapies. However, rehabilitative care is under-recognized and under-utilized in PD and often only utilized in later disease stages, despite research and guidelines demonstrating its positive effects. Currently, there is a lack of consensus regarding fundamental topics related to rehabilitative services in PD. OBJECTIVE: The goal of the international Parkinson's Foundation Rehabilitation Medicine Task Force was to develop a consensus statement regarding the incorporation of rehabilitation in PD care. METHODS: The Task Force, comprised of international multidisciplinary experts in PD and rehabilitation and people directly affected by PD, met virtually to discuss topics such as rehabilitative services, existing therapy guidelines and rehabilitation literature in PD, and gaps and needs. A systematic, interactive, and iterative process was used to develop consensus-based statements on core components of PD rehabilitation and discipline-specific interventions. RESULTS: The expert-based consensus statement outlines key tenets of rehabilitative care including its multidisciplinary approach and discipline-specific guidance for occupational therapy, physical therapy, speech language pathology/therapy, and psychology/neuropsychology across all PD stages. CONCLUSIONS: Rehabilitative interventions should be an essential component in the comprehensive treatment of PD, from diagnosis to advanced disease. Greater education and awareness of the benefits of rehabilitative services for people with PD and their care partners, and further evidence-based and scientific study are encouraged.

(HIIT-The Track) High-Intensity Interval Training for People with Parkinson's Disease: Individual Response Patterns of (Non-)Motor Symptoms and Blood-Based Biomarkers-A Crossover Single-Case Experimental Design.

INTRODUCTION: Physical exercise is receiving increasing interest as an augmentative non-pharmacological intervention in Parkinson's disease (PD). This pilot study primarily aimed to quantify individual response patterns of motor symptoms to alternating exercise modalities, along with non-motor functioning and blood biomarkers of neuroplasticity and neurodegeneration. MATERIALS & METHODS: People with PD performed high-intensity interval training (HIIT) and continuous aerobic exercise (CAE) using a crossover single-case experimental design. A repeated assessment of outcome measures was conducted. The trajectories of outcome measures were visualized in time series plots and interpreted relative to the minimal clinically important difference (MCID) and smallest detectable change (SDC) or as a change in the positive or negative direction using trend lines. RESULTS: Data of three participants were analyzed and engaging in physical exercise seemed beneficial for reducing motor symptoms. Participant 1 demonstrated improvement in motor function, independent of exercise modality; while for participant 2, such a clinically relevant (positive) change in motor function was only observed in response to CAE. Participant 3 showed improved motor function after HIIT, but no comparison could be made with CAE because of drop-out. Heterogeneous responses on secondary outcome measures were found, not only between exercise modalities but also among participants. CONCLUSION: Though this study underpins the positive impact of physical exercise in the management of PD, large variability in individual response patterns to the interventions among participants makes it difficult to identify clear exercise-induced adaptations in functioning and blood biomarkers. Further research is needed to overcome methodological challenges in measuring individual response patterns.

Graded peak cycle ergometer test for cognitively impaired patients with Parkinson's disease: a pilot study.

BACKGROUND: Cognitive decline affects up to 50% of patients with Parkinson's disease (PD) in the course of the disease and may be amenable to exercise interventions. To accurately set adequate training intensities, standardized exercise testing is required but such testing takes considerable time and effort. The aim of this pilot study was to investigate the feasibility of a graded peak cycle ergometer exercise test in cognitively impaired patients with Parkinson's Disease (PD), and to define whether age-predicted maximal heart rate (HRmax) matched measured HRmax. METHODS: A convenience sample of seven patients with PD (Hoehn and Yahr: 2-4, and cognitive impairment (Montreal Cognitive Assessment (MoCA) ≤ 26) completed a graded peak cycle ergometer test to voluntary exhaustion. Borg Rating of Perceived Exertion was used to record the individual's perception of exertion. Pre-defined age-predicted HRmax (calculated as 208-(0.7 × age) was compared with the measured HRmax using Bland-Altman plot and a two-one-sided test. RESULTS: All PD patients completed the graded exercise test between 8-12 minutes, showing therefore 100% compliance to the test protocol. No adverse events occurred. Predicted HRmax and measured HRmax did not differ. CONCLUSION: We demonstrate feasibility of graded peak cycle ergometer testing in PD patients with cognitive impairment. The good correspondence of age-predicted HRmax equation with measured HRmax, in this small sample, may in the future provide clinicians with a tool to define training intensities in cognitively impaired PD, without cardiac disease. However, further research is needed to confirm these results.

Exercise-induced increase in blood-based brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis: A systematic review and meta-analysis of exercise intervention trials.

BACKGROUND: Exercise training may affect the blood levels of brain-derived neurotrophic factor (BDNF), but meta-analyses have not yet been performed comparing pre- and post-intervention BDNF concentrations in patients with multiple sclerosis (PwMS). OBJECTIVE: To perform a meta-analysis to study the influence of exercise on BDNF levels and define components that modulate them across clinical trials of exercise training in adults living with multiple sclerosis (MS). METHOD: Five databases (PubMed, EMBASE, Cochrane Library, PEDro database, CINAHL) were searched up to June 2021. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 13 articles in the meta-analysis, including 271 subjects. To investigate sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. We performed the meta-analysis to compare pre- and post-exercise peripheral levels of BDNF in PwMS. RESULTS: Post-exercise concentrations of serum BDNF were significantly higher than pre-intervention levels (Standardized Mean Difference (SMD): 0.33, 95% CI: [0.04; 0.61], p-value = 0.02). Meta-regression indicated that the quality of the included studies based on the PEDro assessment tool might be a source of heterogeneity, while no significant effect was found for chronological age and disease severity according to the expanded disability status scale. CONCLUSION: This systematic review and meta-analysis shows that physical activity increases peripheral levels of BDNF in PwMS. More research on the effect of different modes of exercise on BDNF levels in PwMS is warranted.

Mild Traumatic Brain Injury Is Associated With Increased Dual-Task Cost During Ambulation: A Preliminary Study.

OBJECTIVE: The aim of the study was to determine the impact of dual-task conditions on mobility after mild traumatic brain injury. DESIGN: Eleven adults with mild traumatic brain injury within 1 wk of injury and 10 age- and sex-matched healthy controls completed gait trials with a single-task condition and three separate dual-task conditions: counting by 1 (low), serial subtraction by 3 (medium), and alternating letters and numbers (high). Dual-task cost was calculated as dual-task cost = ([dual-task performance] - [single-task performance]) / [single-task performance] × 100%. RESULTS: Participants with mild traumatic brain injury ambulated slower than control subjects (P < 0.001). Significant differences in dual-task cost were noted for both group (P < 0.001) and dual-task condition (P = 0.005). Dual-task cost was greater for those with mild traumatic brain injury compared with controls with significant group differences for the low and high cognitive loads (P < 0.05). Only 1 of the 11 individuals with mild traumatic brain injury and 1 of the 10 controls demonstrated gait speed less than 80 cm/sec, which is predictive of community mobility, during any dual-task condition. Dual-task cost exceeded 11.9%, previously determined to be the minimal detectable change in healthy adults, for 9 of the 11 individuals with mild traumatic brain injury compared with 3 of the 10 controls. CONCLUSIONS: Dual-task cost may be a more sensitive measure for impairment during dual-task conditions than gait speed after mild traumatic brain injury.

Testosterone Therapy for the Treatment of Age-Related Hypogonadism: Risks with Uncertain Benefits.

Testosterone replacement therapy has been approved in the United States since the 1950s for men with "classical" hypogonadism. These men have specific and well-recognized hypothalamic, pituitary, or testicular conditions leading to deficient or absent endogenous testosterone. A more controversial treatment population is aging men, many with comorbidities, who have low serum testosterone concentrations compared with young healthy men and who do not have the well-recognized medical conditions that cause "classical" hypogonadism. Testosterone continues to be widely used in these men with "age-related hypogonadism" even though the benefits of testosterone for this use are uncertain and there are important risks, including a potential risk of major adverse cardiac events for the testosterone class, and two testosterone products with increases in blood pressure that can increase the risk of myocardial infarction and stroke. Given the uncertain clinical benefit of testosterone in men with "age-related hypogonadism" in the face of known and potential adverse outcomes, none of the testosterone products is FDA approved for such use.

Exercise interventions for older adults with Alzheimer's disease: a systematic review and meta-analysis protocol.

BACKGROUND: The growing societal and economic impact of Alzheimer's disease (AD) is further compounded by the present lack of disease-modifying interventions. Non-pharmacological intervention approaches, such as exercise, have the potential to be powerful approaches to improve or mitigate the symptoms of AD without added side effects or financial burden associated with drug therapies. Various forms and regiments of exercise (i.e., strength, aerobic, multicomponent) have been reported in the literature; however, conflicting evidence obscures clear interpretation of the value and impact of exercise as an intervention for older adults with AD. The primary objective of this review will be to evaluate the effects of exercise interventions for older adults with AD. In addition, this review will evaluate the evidence quality and synthesize the exercise training prescriptions for proper clinical practice guidelines and recommendations. METHODS: This systematic review and meta-analysis will be carried out by an interdisciplinary collective representing clinical and research stakeholders with diverse expertise related to neurodegenerative diseases and rehabilitation medicine. Literature sources will include the following: Embase, PsychINFO, OVID Medline, and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily. Inclusion criteria are participants with late onset AD and structured exercise interventions with prescribed duration, frequency, and intensity. The primary outcome of this study will center on improved or sustained cognitive functioning. Secondary outcomes will include institutionalization-related outcomes, ability in activities of daily living, mood and emotional well-being, quality of life, morbidity, and mortality. Analysis procedures to include measurement of bias, data synthesis, sensitivity analysis, and assessment of heterogeneity are described in this protocol. DISCUSSION: This review is anticipated to yield clinically meaningful insight on the specific value of exercise for older adults with AD. Improved understanding of diverse exercise intervention approaches and their specific impact on various health- and function-related outcomes is expected to guide clinicians to more frequently and accurately prescribe meaningful interventions for those affected by AD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020175016 .

Qualitative Examination of Voting Empowerment and Participation Among People Living With Traumatic Brain Injury.

OBJECTIVE: To examine political participation after traumatic brain injury (TBI). DESIGN: Qualitative, participatory research via interviews and observations. Each participant was interviewed to discuss their experience of voting in 2007 or 2008. Data were coded using Grounded Theory to develop themes, metacodes, and theories. SETTING: Community. PARTICIPANTS: A total of 57 individuals with history of TBI and 28 family members (N=85). MAIN OUTCOME MEASURES: Not applicable. RESULTS: Four themes emerged from the data: (1) people with TBI have barriers to voting; (2) the voting process can be improved for people with TBI; (3) voting is the responsibility of members of society; and (4) voting is one way we have a voice in society. CONCLUSIONS: The data support the importance of voting as an American right regardless of the presence of disability. While persons with TBI report voting represents their freedom and voice, there may be barriers that can threaten or limit their voice.

High-Intensity Interval Cycle Ergometer Training in Parkinson's Disease: Protocol for Identifying Individual Response Patterns Using a Single-Subject Research Design.

Background: People with Parkinson's disease (PD) experience not only motor problems but also non-motor problems that seriously impede their daily functioning and quality of life. The current pharmacologic treatment of PD is symptomatic, and alternative rehabilitation treatments, which preferably also have a disease-modifying effect and promote neuroplasticity, are needed. Recent studies suggest that high-intensity interval training (HIIT) is promising for promoting neuroplasticity in human PD, with short training time and reduced burden. Biomarkers for neuroplasticity such as brain-derived neurotrophic factor (BDNF) and neurodegeneration (including neurofilament NfL and α-synuclein) may play a role, but their response to HIIT is not well-investigated. Objectives: The aims of this study were (1) to study the effects of 4 weeks of HIIT compared with 4 weeks of continuous aerobic exercise on motor and non-motor outcomes of PD and (2) to investigate the association between HIIT, motor/non-motor performances changes, and blood biomarker levels for neuroplasticity and neurodegeneration. Study Design: Single-subject research design with alternating treatment setup (ABACA) and frequent repeated measurements was used. Each participant received different intervention conditions (B/C) interspersed with baseline periods (A, i.e., ABACA or ACABA), and frequent repeated assessment of outcome measures is done to quantify within-subject, individual response patterns with sufficient power for data analysis. Blood samples were collected once a week in the baseline and training phases (A1 and B/C) and once every 2 weeks in the washout phases (A2 and A3). Intervention: Four subjects with PD on stable dopaminergic medication, two in Hoehn-Yahr stage 1-2, and two in Hoehn-Yahr stage 2.5-3 followed an ABACA or ACABA schedule, consisting of blocks with 30-min sessions of "B" (HIIT) or 50-min sessions of "C" [continuous aerobic exercise (CAE)] 3×/week for 4 weeks, separated by baseline "A" periods of 8 weeks for a total duration of 28 weeks. Outcome Measures: Outcome measures include disease status [Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)], blood biomarkers (BDNF, Nfl, and α-synuclein), measures for functional mobility (including an activity tracker), and activities of daily living, as well as cognition, mood, biorhythm (sleeping problems), and quality of life. Data Analysis: Visual analysis of trends in level, slope, and variability in response patterns was carried out, confirmed by longitudinal regression analysis with phase (ABACA) as the independent variable.

Use of an instrumented dual-task timed up and go test in children with traumatic brain injury.

BACKGROUND: Wearable sensors have allowed researchers to instrument tests of gait-related mobility, including the widely used timed 'up-and-go' test (TUG). Currently, there is a lack of instrumented test data on whether children with moderate to severe traumatic brain injury (TBI) perform differently on the TUG compared to typically developed (TD) controls during a cognitive-motor task. RESEARCH QUESTION: The aim was to explore the effects of a cognitive-motor task on TUG subcomponents among children with TBI compared to TD children. METHODS: This observational cross-sectional study included 12 children with moderate to severe TBI (6 males and 6 females, age 10.5 ±â€¯1.5 years of age) and 10 age and sex-matched TD controls (5 males and 5 females, 10.4 ±â€¯1.3 years of age). Each participant completed 6 trials of the TUG wearing a single inertial measurement unit sensor at a self-selected walking pace while listening to an array of 10 randomly presented single digits during each TUG trial. RESULTS: Total time to complete the TUG was not significantly different between groups. The cognitive-motor task led to significantly lower mean turn and peak turn angular velocity values during the turn-around-the-cone and turn-before-sitting TUG subcomponents in children with TBI compared to the TD controls (p ≤ 0.05). Additionally, the cognitive-motor task led to significantly lower values for maximum torso flexion to extension angle, peak flexion and extension angular velocity and peak vertical acceleration for the sit-to-stand subcomponent (p < 0.05). Peak flexion angular velocity during the stand-to-sit subcomponent was lower for the TBI group compared to the children with TD (p < 0.05). SIGNIFICANCE: The study provides new insights into the performance of complex gait-related mobility tasks in the context of an instrumented TUG among children with moderate to severe TBI. Our results highlight the potential benefits of outfitting pediatric inpatients with an IMU while completing the TUG.