Long-term effects of exercise and physical therapy in people with Parkinson disease

Mak, Kit Yi; Wong-Yu, Irene S.K.; Shen, Xia; Chung, Chloe Lau Ha

doi:10.1038/nrneurol.2017.128

Cited by 373 publications

(347 citation statements)

References 158 publications

Supporting

Mentioning

298

Contrasting

Unclassified

Order By: Relevance

“…Proposed mechanisms demonstrated in preclinical models include anti-inflammatory, antioxidant, promitochondrial, trophic, and anti-synuclein effects, and small studies in PD patients have shown increased cortical motor excitability, elevated striatal dopamine D2 receptor binding, increased serum levels of brainderived neurotrophic factor, and improvements in gray matter volumes (for a review, see ref. 68 ). Whether these findings truly represent central neuroplastic changes that will have a long-term impact on the natural history of the neurodegenerative process or simply central consequences of improved fitness and physical training will only be established when reliable biomarkers for the disease status become available.…”

Section: Other Treatment Categoriesmentioning

confidence: 99%

Disease Modification in Parkinson's Disease: Current Approaches, Challenges, and Future Considerations

2018

View full text Add to dashboard Cite

The greatest unmet therapeutic need in Parkinson's disease is the development of treatment that slows the relentless progression of the neurodegenerative process. The concept of "disease modification" encompasses intervention types ranging from those designed to slow the underlying degeneration to treatments directed at regenerating or replacing lost neurons. To date all attempts to develop effective disease-modifying therapy have failed. Many reasons have been proposed for these failures including our rudimentary understanding of disease pathogenesis and the assumption that each targeted mechanisms of disease apply to most patients with the same clinical diagnosis. Here we review all aspects of this broad field including general concepts and past challenges followed by a discussion of treatment approaches under the following 4 categories: (1) α-synuclein, (2) pathogenic mechanisms distinct from α-synuclein (most also potentially triggered by α-synuclein toxicity), (3) non-SNCA genetic subtypes of "PD," and (4) possible disease-modifying interventions not directly influencing the underlying PD pathobiology. We emphasize treatments that are currently under active clinical development and highlight a wide range of important outstanding questions and concerns that will need to be considered to advance the field of disease modification in PD. Critically, it is unknown whether the dysfunctional molecular pathways/organelles amenable to modification occur in a sequential fashion across most clinically affected individuals or manifest differentially in independent molecular subtypes of PD. It is possible that there is no "order of disruption" applicable to most patients but, rather, "type of disruption" applicable to subtypes dependent on unknown factors, including genetic variability and other causes for heterogeneity in PD. Knowing when (early vs late), which (eg, synaptic transmission, endosomal sorting and maturation, lysosomal degradation, mitochondrial biogenesis), and in whom (PD subtype) specific disrupted cell pathways are truly pathogenic versus compensatory or even protective, will be important in considering the use of single or combined ("cocktails") putative disease-modifying therapies to selectively target these processes. Beyond the current phase 2 or 3 studies underway evaluating treatments directed at oxidative stress (inosine), cytosolic Ca (isradipine), iron (deferiprone), and extracellular α-synuclein (passive immunization), and upcoming trials of interventions affecting c-Abl, glucagon-like peptide-1, and glucocerebrosidase, it might be argued that further trials in populations not enriched for the targeted pathogenic process are doomed to repeat the failures of the past. © 2018 International Parkinson and Movement Disorder Society.

show abstract

Section: Other Treatment Categoriesmentioning

confidence: 99%

Disease Modification in Parkinson's Disease: Current Approaches, Challenges, and Future Considerations

2018

View full text Add to dashboard Cite

show abstract

“…[9][10][11] Given the long prodromal stage of PD development, reverse causality cannot be excluded. Finally, the biological mechanisms underlying exercise and a lower PD risk are largely speculative, but may involve increased neuroplasticity and brain-derived neurotrophic factors 12 and a reduction in neuroinflammation. 10,13 Moderate coffee consumption (3-5 cups/day) is associated with lower risk of multiple CV outcomes.…”

Section: Factors That Have Concordant Associationsmentioning

confidence: 99%

Understanding the Links Between Cardiovascular Disease and Parkinson's Disease

et al. 2019

View full text Add to dashboard Cite

Studies investigating the associations between genetic or environmental factors and Parkinson's disease (PD) have uncovered a number of factors shared with cardiovascular disease, either as risk factors or manifestations of cardiovascular disease itself. Older age, male sex, and possibly type 2 diabetes are examples. On the other hand, coffee consumption and physical activity are each associated with a lower risk of both PD and cardiovascular disease. This observation raises questions about the underlying pathophysiological links between cardiovascular disease and PD. There is evidence for common mechanisms in the areas of glucose metabolism, cellular stress, lipid metabolism, and inflammation. On the other hand, smoking and total/low‐density lipoprotein cholesterol appear to have opposite associations with cardiovascular disease and PD. Thus, it is uncertain whether the treatment of cardiovascular risk factors will impact on the onset or progression of PD. The available data suggest that a nuanced approach is necessary to manage risk factors such as cholesterol levels once the associations are better understood. Ultimately, the choice of therapy may be tailored to a patient's comorbidity profile. This review presents the epidemiological evidence for both concordant and discordant associations between cardiovascular disease and PD, discusses the cellular and metabolic processes that may underlie these links, and explores the implications this has for patient care and future research. © 2019 International Parkinson and Movement Disorder Society

show abstract

“…Additionally, impaired gait negatively affects a person's social participation, which can further reduce quality of life (Hammarlund, Andersson, Andersson, Nilsson, & Hagell, 2014). Gait training is therefore an integral approach within PD rehabilitation, and there is strong evidence that improvements in walking can be maintained up to 6 months after training has ceased (Mak, Wong‐Yu, Shen, & Chung, 2017). Assessment of walking is not only an essential marker of rehabilitation effectiveness, but can also potentially identify those at risk for physical inactivity or falls who require targeted preventive efforts (Canning, Paul, & Nieuwboer, 2014).…”

Section: Introductionmentioning

confidence: 99%

Patient‐reported and performance‐based measures of walking in mild–moderate Parkinson's disease

et al. 2018

View full text Add to dashboard Cite

BackgroundKnowledge of the relationships between patient‐reported and performance‐based walking measures in Parkinson's disease (PD) should inform clinical decision‐making. The Walk‐12G reliably captures perceived walking difficulties but has not been compared to performance‐based walking in laboratory or free‐living settings or across different groups.ObjectivesTo investigate the relationship between patient‐reported walking difficulties (Walk‐12G) and performance‐based walking in laboratory and free‐living conditions and to determine whether the Walk‐12G can distinguish between the subgroups, (i) people with/without PD and (ii) mild/moderate disease stages.MethodsForty‐seven people without and 49 people with PD (Hoehn and Yahr stage II and III) were assessed in relation to patient‐reported walking difficulties (Walk‐12G scale); spatiotemporal gait characteristics (Pace; Rhythm; Asymmetry; Variability; and Postural control) using a laboratory‐based electronic walkway; and walking behavior (mean steps/day and minutes of brisk walking/day) using accelerometers in free‐living conditions.ResultsThe Walk‐12G correlated moderately with the spatiotemporal domain step velocity (r = −0.46) and walking behavior, measured as mean steps/day (r = −0.46). Weaker correlations were observed for step length and minutes spent in brisk walking (r = −0.36 and r = −0.35, respectively). Poor correlations were observed for all other spatiotemporal domains. The Walk‐12G could distinguish between people with and without PD (Effect size, r = 0.82) and between those at mild/moderate disease stages (r = 0.34).ConclusionsPerceived walking difficulties showed weak to moderate associations with performance‐based measures of walking in mild–moderate PD. As the strongest associations were observed for step velocity and walking behavior, targeting these specific gait aspects could improve perceived walking difficulties in daily life.

show abstract

Long-term effects of exercise and physical therapy in people with Parkinson disease

Cited by 373 publications

References 158 publications

Disease Modification in Parkinson's Disease: Current Approaches, Challenges, and Future Considerations

Disease Modification in Parkinson's Disease: Current Approaches, Challenges, and Future Considerations

Understanding the Links Between Cardiovascular Disease and Parkinson's Disease

Patient‐reported and performance‐based measures of walking in mild–moderate Parkinson's disease

Contact Info

Product

Resources

About