Fall risk factors and exercise in Parkinson's disease

Abstract

Many people with Parkinson’s disease fall frequently and recurrently. The consequences of falls can be devastating, far reaching and costly. Unfortunately, medications for Parkinson’s disease do not appear to prevent falls. The overall aim of the studies in this thesis was to evaluate and explore exercise interventions with the potential to reduce fall risk in people with Parkinson’s disease. Leg muscle weakness, freezing of gait and reduced balance are risk factors for falls which are potentially remediable with exercise in people with Parkinson’s disease. However, there is a paucity of research into the effects of exercise training on fall risk in this group. A randomised controlled trial with blinded assessment was conducted to assess the effect on fall risk of a six-month exercise program which targeted these risk factors compared with usual care in people with Parkinson’s disease. Forty-eight participants with Parkinson’s disease who had fallen or were at risk of falling were randomised to the exercise or control group. The exercise group attended a monthly exercise class and performed exercises at home, such that exercises were performed three times per week. Both groups received falls prevention advice. The primary outcome measure was a Parkinson’s disease fall risk score (% risk of falling) – an algorithm consisting of weighted contributions from knee extensor muscle strength of the weaker leg, balance in standing and freezing of gait. Secondary outcome measures included measures of the targeted risk factors as well as physical abilities, fear of falling and quality of life. The exercise group showed a 7% greater improvement than the control group in the Parkinson’s disease falls risk score, but this was not statistically significant (95% Confidence Interval (95% CI) -20 to 5) and the clinical relevance of this small reduction is uncertain. There were statistically significant improvements in the exercise group compared to the control group for two secondary outcomes which were not part of the falls risk score: Freezing of Gait Questionnaire (mean between-group difference = -2.8, 95% CI -5.4 to -0.3) and timed sit to stand (mean between-group difference = -1.9 s, 95% CI -3.6 to -0.2). There were non-significant trends toward greater improvements in the exercise group for other measures that were not part of the falls risk score, including muscle strength (stronger leg P = 0.06), fast walking speed (P = 0.21) and fear of falling (P = 0.10), but not for balance or quality of life. The exercise group had no major adverse events. Therefore, a minimally-supervised exercise program for mobile people with Parkinson’s disease who are at risk of falling might reduce overall risk of falling and improve muscle strength and can improve freezing and sit to stand speed. The results of this study have informed the implementation of a larger randomised controlled trial to assess whether this relatively small reduction in fall risk translates into actual falls prevented. Reduced balance is a commonly experienced risk factor for falls in people with Parkinson’s disease. However, the effect of exercise and motor training on balance in people with Parkinson’s disease was unclear and had not been subjected to meta-analysis. A systematic review with random effects meta-analysis was conducted to determine the effects of exercise and motor training on balance-related activity performance in people with Parkinson’s disease. Meta-regression was used to investigate if the total dose of exercise and the presence of highly-challenging balance training are associated with the size of the effect of intervention on balance-related activities. Seven electronic databases were searched in September 2009. Trials were included if they were published randomised controlled trials of an intervention designed for people with Parkinson’s disease that compared exercise and/or motor training with a no intervention or placebo control group, and were evaluated with a measure of balance. The primary outcome measures were balance-related activity performance and falls. The balance-related activity performance measure involved pooling the single most comprehensive balance measure from each trial and included (in order of priority): the Berg Balance Scale, the Timed Up and Go, gait velocity/time, turning time, sit to stand time, Functional Reach and single leg stand time. The outcomes were included in this order to prioritise outcomes the author considered to be the most global measures of balance or balance-related activity performance. Secondary outcome measures included these individual balance measures as discrete measures as well as step/stride length and cadence. The balance-related activity performance meta-analysis included 15 trials with 747 participants and the falls meta-analysis included 2 trials with 250 participants. The pooled estimate of the effect showed that exercise and motor training significantly improved balance-related activity performance (Hedges’ g = 0.34, 95% CI 0.11 to 0.57, P = 0.004) but there was no evidence of an effect on the proportion of fallers (risk ratio = 1.02; 95% CI 0.66 to 1.58, P = 0.94). Exercise and motor training was found to have a small positive effect on gait velocity and step/stride length as well as a moderate effect on turning time. The greatest relative effects of exercise and motor training on balance-related activity performance tended to occur in programs with highly-challenging balance training (P = 0.16), but there was no evidence of an association with the total dose of exercise (P = 0.98). There were non-significant trends towards improvement for most other outcome measures. Therefore, exercise and motor training can improve the performance of balance-related activities in people with Parkinson’s disease. However, further research is required to determine if falls can be prevented using exercise approaches in this population. While leg muscle weakness is a risk factor for falls in people with Parkinson’s disease, muscle strength is not commonly considered to be affected by the disease process and muscle weakness is usually not apparent on clinical examination. However, people with Parkinson’s disease often report feeling weak. One of the reasons for this discrepancy is the presence of bradykinesia (slowness of movement), making it difficult to ascertain if people with Parkinson’s disease are truly weak, or just slow to develop muscle force. The measurement of muscle power (force × velocity of contraction) has the potential to clarify the relationship between muscle weakness and bradykinesia in people with Parkinson’s disease. Furthermore, in the general older population, muscle power appears to be a better predictor of falls and physical activity performance than muscle strength. While modern variable resistance technology has the ability to measure muscle strength without the interference of bradykinesia, as well as muscle power, these measurements had never been reported in people with Parkinson’s disease. A descriptive study with two parts was conducted utilising this technology. Part one aimed to determine if the leg extensor muscles of people with mild to moderate Parkinson’s disease are weaker and/or less powerful than a neurologically-normal control group, and determine the relative contributions of force and movement velocity to muscle power in people with Parkinson’s disease. The leg extensor muscle strength (N) and power (W) of 40 participants with Parkinson’s disease and 40 neurologically-normal participants of similar age and gender were assessed. The Parkinson’s disease group were 16% weaker (mean between-group difference = 172N, 95% CI 28 to 315) and 22% less powerful (mean between-group difference = 124 W, 95% CI 32 to 216) than the control group. Muscle power was disproportionately reduced at light to medium loads due to reduced movement speed, whereas at heavy loads this bradykinesia was no longer apparent. These results suggest that reduced muscle power at lighter loads arises from weakness and bradykinesia combined, but at heavier loads arises primarily from weakness. Part two aimed to examine the relationship of muscle strength/power with walking speed and past falls in people with Parkinson’s disease. Walking velocity over 10 m and the number of falls experienced in the prior 12 months was recorded for the 40 aforementioned participants with Parkinson’s disease. Muscle power was found to explain more than half the variance in walking velocity (R2 = 0.54) and remained significantly associated with walking velocity in models which included a measure of Parkinson’s disease severity. Furthermore, participants with low muscle power were 6 times more likely to report multiple falls in the prior 12 months than those with high muscle power (Odds Ratio = 6.0, 95% CI 1.1 to 33.3), although this association between falls and power was no longer significant in models which included Parkinson’s disease severity. However, muscle power was consistently found to explain as much or more of the variation in walking velocity, and was more strongly associated with past falls, than muscle strength. Adequate leg extensor muscle power therefore seems likely to be important for maximising mobility and reducing fall risk in people with Parkinson’s disease. A Parkinson’s disease fall risk score that includes leg muscle power instead of strength should be trialled, and the effect of muscle power training on walking speed and falls in people with Parkinson’s disease warrants investigation. Overall, the research presented in this thesis provides three pieces of evidence related to exercise and fall risk in people with Parkinson’s disease. Firstly, exercise interventions can improve freezing of gait and are likely to improve muscle weakness and balance in people with Parkinson’s disease. Improvements in these potentially remediable risk factors for falls may lead to a reduction in the overall risk of falling in this group. Secondly, it appears that muscle weakness and reduced muscle power are due, in part, to the disease process itself. Finally, reduced muscle power is likely to also be a risk factor for falls in Parkinson’s disease and may be more important to address with exercise interventions than muscle weakness. These results provide evidence to assist clinicians and researchers in devising exercise programs for people with Parkinson’s disease. Any reduction in falls in this group will improve the quality of life of people with Parkinson’s disease and their carers and help to reduce pressure on health care systems.