Background: To date, no medication has slowed the progression of Parkinson’s disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline. Methods: This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60–65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80–85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity. Discussion: SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health. Trial registration: ClinicalTrials.govNCT04284436. Registered on February 25, 2020.

Introduction. Understanding how exercise affects individuals with varying levels of functional ability will provide further insight into the role of exercise during the aging process. It will also aid in the development of exercise programs that are appropriate for a wider spectrum of older adults. Specifically it was the primary aim of this study to determine and compare the effects of 10 weeks of community-based exercise on the cardiovascular endurance, muscular strength, flexibility, and balance fitness components of older adult women with high and moderate-low levels of physical function. Methods. Participants were placed in either the high functioning (n = 13) or moderate/low functioning (n = 17) groups based on their level of physical functioning. Fitness components were measured by the Senior Fitness Test and physical function was determined by the Composite Physical Function scale. Results. The results of the 3 × 2 mixed ANOVA statistical analysis showed no significant interaction effect for time ⁎ group for any of the six subtests (chair stand, arm curls, 2-minute step, chair sit-and-reach, back scratch, and 6-foot up-and-go) of the SFT. However, the main effect of time was significant for all fitness components and the main effect of group was significant for all fitness components except lower extremity flexibility. Discussion. Community-based exercise programs offering a variety of exercise types to people with varying levels of functional ability can be useful in maintaining or improving fitness and independence. These programs may also be capable of improving the self-efficacy of lower functioning older adults toward performing daily tasks.

Gait dysfunction and postural instability are two debilitating symptoms in persons with Parkinson's disease (PD). Tai Chi exercise has recently gained attention as an attractive intervention for persons with PD because of its known potential to reduce falls and improve postural control, walking abilities, and safety at a low cost. The purpose of this report is to investigate the effect of Tai Chi exercise on dynamic postural control during gait initiation and gait performance in persons with idiopathic PD, and to determine whether these benefits could be replicated in two different environments, as complementary projects. In these two separate projects, a total of 45 participants with PD were randomly assigned to either a Tai Chi group or a control group. The Tai Chi groups in both projects completed a 16-week Tai Chi exercise session, while the control groups consisted of either a placebo (i.e., Qi-Gong) or non-exercise group. Tai Chi did not significantly improve Unified Parkinson's Disease Rating Scale Part III score, selected gait initiation parameters or gait performance in either project. Combined results from both projects suggest that 16 weeks of class-based Tai Chi were ineffective in improving either gait initiation, gait performance, or reducing parkinsonian disability in this subset of persons with PD. Thus the use of short-term Tai Chi exercise should require further study before being considered a valuable therapeutic intervention for these domains in PD.

Parkinson's disease (PD), an intractable condition impairing motor and cognitive function, is imperfectly treated by drugs and surgery. Two priority issues for many people with PD are OFF-time and cognitive impairment. Even under best medical management, three-fourths of people with PD experience “OFF-time” related to medication-related motor fluctuations, which severely impacts both quality of life and cognition. Cognitive deficits are found even in newly diagnosed people with PD and are often intractable. Our data suggest that partnered dance aerobic exercise (PDAE) reduces OFF-time on the Movement Disorders Society Unified Parkinson Disease Rating Scale-IV (MDS-UPDRS-IV) and ameliorates other disease features, which motivate the PAIRED trial. PDAE provides AE during an improvisational, cognitively engaging rehabilitative physical activity. Although exercise benefits motor and cognitive symptoms and may be neuroprotective for PD, studies using robust biomarkers of neuroprotection in humans are rare. We propose to perform a randomized, controlled trial in individuals with diagnosed mild–moderate PD to compare the efficacy of PDAE vs. walking aerobic exercise (WALK) for OFF-time, cognition, and neuroprotection. We will assess neuroprotection with neuromelanin-sensitive MRI (NM-MRI) and iron-sensitive (R2*) MRI sequences to quantify neuromelanin loss and iron accumulation in substantia nigra pars compacta (SNc). We will use these biomarkers, neuromelanin loss, and iron accumulation, as tools to chart the course of neurodegeneration in patients with PD who have undergone long-term (16 months) intervention. We will randomly assign 102 individuals with mild–moderate PD to 16 months of PDAE or WALK. The 16-month intervention period will consist of Training (3 months of biweekly sessions) and Maintenance (13 months of weekly sessions) phases. We will assess participants at baseline, 3 months (immediately post-Training), and 16 months (immediately post-Maintenance) for OFF-time and behaviorally and physiologically measured cognition. We will acquire NM-MRI and R2* imaging data at baseline and 16 months to assess neuroprotection. We will (1) examine effects of Training and Maintenance phases of PDAE vs. WALK on OFF-time, (2) compare PDAE vs. WALK at 3 and 16 months on behavioral and functional MRI (fMRI) measures of spatial cognition, and (3) compare PDAE vs. WALK for effects on rates of neurodegeneration.

Recent stroke studies have shown that the ipsi-lesional thalamus longitudinally and significantly decreases after stroke in the acute and subacute stages. However, additional considerations in the chronic stages of stroke require exploration including time since stroke, gender, intracortical volume, aging, and lesion volume to better characterize thalamic differences after cortical infarct. This cross-sectional retrospective study quantified the ipsilesional and contralesional thalamus volume from 69 chronic stroke subjects’ anatomical MRI data (age 35–92) and related the thalamus volume to time since stroke, gender, intracortical volume, age, and lesion volume. The ipsi-lesional thalamus volume was significantly smaller than the contra-lesional thalamus volume (t(68) = 13.89, p < 0.0001). In the ipsilesional thalamus, significant effect for intracortical volume (t(68) = 2.76, p = 0.008), age (t(68) = 2.47, p = 0.02), lesion volume (t(68) = − 3.54, p = 0.0008), and age*time since stroke (t(68) = 2.46, p = 0.02) were identified. In the contralesional thalamus, significant effect for intracortical volume (t(68) = 3.2, p = 0.002) and age (t = − 3.17, p = 0.002) were identified. Clinical factors age and intracortical volume influence both ipsi- and contralesional thalamus volume and lesion volume influences the ipsilesional thalamus. Due to the cross-sectional nature of this study, additional research is warranted to understand differences in the neural circuitry and subsequent influence on volumetrics after stroke.

We have previously shown that aerobic exercise improves measures of verbal fluency in older adults, and such an improvement is correlated with improved cardiovascular reserve (i.e., estimates of VO2). Due to increasing popularity in computer-based cognitive training, we explored whether the addition of cognitive training to aerobic exercise would further enhance the beneficial cognitive impact of exercise. Therefore, this study sought to test the hypothesis that a cognitive training regimen alone would directly improve executive function and that this effect would be potentiated with the addition of aerobic exercise. The interventions lasted 12 weeks, and cognitive assessments were taken immediately prior to and after the interventions. We found that only the groups employing aerobic exercise showed improvements in verbal fluency (semantic and letter) and cardiovascular fitness with no other executive functions being significantly impacted. Cognitive training alone was associated with decreased verbal fluency. These data replicate previous findings which indicate that aerobic exercise may have a remedial or mitigating effect of cognitive decline. In addition, they provide evidence that the addition of concurrent cognitive training to an aerobic exercise program does not provide synergistic improvement in executive functions.

Background: Epidemiological and objective studies report an association between sedentary time and lower risk of the metabolic syndrome (MetS) and its risk factors in young and middle-age adults. To date, there is a lack of objective data on the association between sedentary time and MetS among older adults. Methods: The association between objectively measured sedentary time (accelerometry) with MetS and MetS components was examined in a large sample of older adults with mobility limitations (N = 1198; mean age = 78.7 ± 5.3 years) enrolled in the Lifestyle Interventions and Independence for Elders (LIFE) study. Participants were divided into tertiles according to percentage of daily sedentary time, and the relation between sedentary time with MetS and MetS components was examined after adjusting for age, sex, ethnicity, and BMI. Results: Participants in the highest sedentary time tertile had significantly higher odds of MetS (OR = 1.54) (95% CI 1.13 to 2.11) in comparison with participants in the lowest tertile (p = 0.03). Participants in the highest sedentary time tertile had larger waist circumference (p = 0.0001) and lower HDL-C (p = 0.0003) than participants in the lowest sedentary time tertile. Conclusions: Sedentary time was strongly related to higher odds of MetS. These results, based on objectively measured sedentary time, suggest that sedentary time may represent an important risk factor for the development of MetS in older adults with high likelihood for disability.

The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

Objective: We have previously demonstrated that aerobic exercise improves upper extremity motor function concurrent with changes in motor cortical activity using task-based functional magnetic resonance imaging (fMRI). However, it is currently unknown how a 12-week aerobic exercise intervention affects resting-state functional connectivity (rsFC) in motor networks. Previous work has shown that over a 6-month or 1-year exercise intervention, older individuals show increased resting state connectivity of the default mode network and the sensorimotor network (Voss et al., 2010b; Flodin et al., 2017). However, the effects of shorter-term 12-week exercise interventions on functional connectivity have received less attention. Method: Thirty-seven sedentary right-handed older adults were randomized to either a 12-week aerobic, spin cycling exercise group or a 12-week balance-toning exercise group. Resting state functional magnetic resonance images were acquired in sessions PRE/POST interventions. We applied seed-based correlation analysis to left and right primary motor cortices (L-M1 and R-M1) and anterior default mode network (aDMN) to test changes in rsFC between groups after the intervention. In addition, we performed a regression analysis predicting connectivity changes PRE/POST intervention across all participants as a function of time spent in aerobic training zone regardless of group assignment. Results: Seeding from L-M1, we found that participants in the cycling group had a greater PRE/POST change in rsFC in aDMN as compared to the balance group. When accounting for time in aerobic HR zone, we found increased heart rate workload was positively associated with increased change of rsFC between motor networks and aDMN. Interestingly, L-M1 to aDMN connectivity changes were also related to motor behavior changes in both groups. Respective of M1 laterality, comparisons of all participants from PRE to POST showed a reduction in the extent of bilateral M1 connectivity after the interventions with increased connectivity in dominant M1. Conclusion: A 12-week physical activity intervention can change rsFC between primary motor regions and default mode network areas, which may be associated with improved motor performance. The decrease in connectivity between L-M1 and R-M1 post-intervention may represent a functional consolidation to the dominant M1. Topic Areas: Neuroimaging, Aging.

Objective: Locomotor adaptation enables safe, efficient navigation among changing environments. We investigated how healthy young (HYA) and older (HOA) adults and persons with Parkinson's disease (PD) adapt to walking on a split-belt treadmill, retain adapted gait parameters during re-adaptation, and store aftereffects to conventional treadmill walking. Methods: Thirteen PD, fifteen HYA, and fifteen HOA walked on a split-belt treadmill for ten minutes with one leg twice as fast as the other. Participants later re-adapted to the same conditions to assess retention of the split-belt gait pattern. After re-adaptation, we assessed aftereffects of this pattern during conventional treadmill walking. Results: Persons with PD exhibited step length asymmetry throughout many adaptation and adaptive learning conditions. Early adaptation was similar across groups, though HYA and HOA continued to adapt into late adaptation while PD did not. Despite pervasive step length asymmetry among conditions which were symmetric in HYA and HOA, persons with PD demonstrated significant step length aftereffects during conventional treadmill walking after split-belt walking. Conclusions: Though they may exhibit a default asymmetry under various walking conditions, persons with PD can adapt and store new walking patterns. Significance: Locomotor adaptation therapy may be effective in ameliorating asymmetric gait deficits in persons with PD.