Could different types of exercise (e.g. aerobic versus strength training) offer different outcomes from a neurological or symptomatic standpoint?

Since research in healthy persons show very specific responses and adaptations to exercise protocols, I expect such specific adaptations in persons with PD.  For instance, since strength is adversely affected in persons with PD, one should expect a specific adaptation of increased strength due to resistance training in persons with PD.  Since other factors such as the rate of force development can be affected by specific training in healthy persons, such subtle manipulations of acute training variables should be examined in the context of PD.

We are in our 3^rd year of conducting a study comparing the efficacy of 3 exercise models for gait-related disability in PD.  While the results of this study will not be known for some time yet, there are a number of things we have learned along the way.

1)    As the Research Question suggests, there is an important distinction between symptomatic benefits and neuronal adaptations.  Nonetheless, both of these routes may result in disease modification (although this term is more often used to infer neuronal changes).  From the standpoint of the scientist, considerable excitement would result from even scant evidence of neuronal adaptation, no less neuroprotection.  But from the patient’s perspective, delay of loss of ambulation is the key to maintaining independent function- whether it is related to symptomatic relief or neuronal adaptation.

2)    In our study, PD patients are randomized to 1) aerobic treadmill exercise, 2) treadmill walking without aerobic stimulus, or 3) muscle strengthening exercise (lower body).  These 3 exercise models reflect different profiles of effects e.g. aerobic exercise should result in the greatest degree of cardiovascular conditioning and resistance exercise should result in the greatest improvement in leg strength.  Interestingly, treadmill walking without aerobic stimulus may be the most interesting arm of the study since if simple gait repetition is effective, this suggests that neuronal adaptations result from locomotor training.

3)     It does seem likely that different types of exercise will have different results.  And it is also likely that different neurologic disorders will benefit from different exercise approaches.  In respect to PD, our patient’s descriptions of heaviness of the limbs and fatigue are likely to reflect a level of increased effort to perform a given amount of work (as compared to a healthy adult).  In other words, the presence of parkinsonism is likely to respond to types of exercise in a disease-specific manner that we would anticipate to be different than the response of an individual with a paretic limb.

4)    The questioner mentions measurement of outcomes in exercise trials.  Outcome measures need to be carefully chosen and well matched to the selected exercise approach.  For example in our study, preliminary data analysis has not shown effects of exercise on the motor UPDRS.  Of course, there are very few points of the motor UPDRS devoted to gait, so this is not an ideal measure for a treadmill exercise trial.

5)    Overall, when describing the study of exercise to people with PD, I often describe a “laundry list” of scientific questions that will require multiple studies as we go forward. 

• Is exercise effective for PD symptoms?
• What symptoms respond best?
• At what point in the course of PD, is exercise most effective?
• What intensity and duration of exercise is required?
• How long do the effects last?
• What type(s) of exercise are effective?
• Is exercise effective for both motor and non-motor symptoms?
• Does exercise delay disability?

We have our work cut out for us!

I would agree with the remarks made by Brian Schilling. What you train is what will improve, and this likely applies to PD as well. We currently perform a large MJ Fox sponsored trial in 700 patients, examining whether behavioural changes - increasing overall daily activities - have beneficial clinical effects in PD. We first need large and adequately powered studies to examine the merits of isolated interventions before we can start comparing them.

Another aspect to consider is the central vs. peripheral effect of exercise, and the effects beyond the neuromuscular system.  Strength training may improve measures of bone density, which may help to reduce fractures from potential falls in this population. This again stresses the develpment of very specific exercise programs based on research on the acute training variables (mode,rest periods, load, etc.)

Interesting discussion.   Our work has shown that pedaling rate is important in motor improvements.  We also showed upper extremity improvements with a lower extremity exercise-- interesting in terms of neural drive.  We are now looking more carefully into the rate and intensity of cycling and how that affects motor function.  Right now, it appears that this type of exercise can reduce tremor but it does not have as great of an effect on gait and posture.  I would predict that different types of exercise are necessary depending on the primary symptoms of the individual. 

Many patients with Parkinson's disease (PD) suffer from cognitive dysfunction (especially executive and visuospatial) (Uc et al., 2005). Even in the absence of dementia, cognitive dysfunction in PD can impair critical activities of daily living such as driving (Uc et al., 2007; Uc et al., 2006a; Uc et al., 2006b).  There is increasing evidence of beneficial effects of aerobic exercise on cognition in normal aging (Angevaren et al., 2008) and Alzheimer’s disease (Lautenschlager et al., 2008). Modest increases in cardiovascular fitness with aerobic exercise (e.g., brisk walking) reduce decline in executive functions and visuospatial abilities in the elderly, possibly by enhanced neuroplasticity due to increase of trophic factors and reduction of inflammatory processes in the brain (Colcombe et al., 2004). A meta-analysis shows that resistance training can augment the cognitive benefits of aerobic exercise in aging (Colcombe et al., 2003). Preliminary studies indicate that patients with mild-moderate PD can tolerate aerobic exercise programs and show improvements in cardiovascular fitness and motor function (Bergen et al., 2002; Juncos et al., 2006; Rodrigues et al., 2006; Burini et al., 2006).

 We found in a cross-sectional pilot study of mild-moderate PD (Hoehn-Yahr stage I-III, not demented) that cardiovascular fitness (as indexed by VO₂max) was an independent predictor of executive functions, visuospatial abilities, and mobility (Uc et al., 2008). Cardiovascular fitness was associated with brain activation patterns on functional MRI (fMRI), and regional volume differences on voxel based morphometric (VBM)MRI that correlated with better cognitive performance (Uc et al., 2008).

Currently, we are conducting a preliminary clinical trial funded by the US Department of Veterans Affairs to determine if aerobic exercise intervention in mild-moderate (non-demented, ambulatory) PD demonstrates sufficient cardiovascular and neurobiological effects to merit a subsequent definitive clinical trial to test its efficacy on improving cognitive performance (ClinicalTrials.gov Identifier: NCT00784563, PI: Uc). We are measuring the neurobiologic effects of this intervention (brisk walking, x3/week for 6 months) using fMRI, VBM-MRI, homocysteine, trophic factors, and markers of inflammation. Our study also aims to determine the best aerobic exercise regimen (continuous vs. interval, group vs. home- based) for a future Phase III trial. Other research questions may include if to combine aerobic exercise with another modality (e.g., resistance) or exercise imparts its potential effect on cognition by symptomatic and/or neuroprotective effects.

Juncos JL, Haber M, Hass CS, Waddell D, Gregor R, Wolf SL. A controlled study of aerobic exercise and Chinese exercise modalities in Parkinson disease. Neurology 2006; 314- [abstract]

Uc EY, Doerschug K, Mehta S, Rizzo M, Erickson K, Darling W, Anderson S, Rodnitzsky R, Mine J, Kramer A, Grabowski T. Cardioivascular fitness and cognition in mild-moderate Parkinson's disease. Neurology 2008; A290 [abstract]

In response to Michael Rogan's comments on the impact of PD specific cognitive / psychological symptoms on adherence to exercise - we have found that depression, apathy, lack of motivation etc...can certainly impact participation and adherence to exercise.  In a study funded by the Davis Phinney Foundation, we (Marie Saint-Hilaire, BU; Cathi Thomas, BU; Lee Dibble, Univ of Utah; Gammon Earhart, Wash U; Matt Ford, UAB) are investigating the exercise habits, attitudes and beliefs of people with PD and the barriers and facilitators of exercise.  For example, we are exploring some of the following questions:

Do people with PD believe that exercise will lead to improvements in quality of life, mobility etc...or do they believe they may get worse by exercising? 

Do people with PD feel they are capable of exercising despite their symptoms? 

What are the barriers that limit participation in exercise in people with PD - is it their disease specific physical impairments such as rigidity and bradykinesia or nonmotor impairments such as apathy or depression or their beliefs about the limited benefits of exercise in the presence of their disease?  

In addition, the following questions need to be answered to optimize exercise adherence:

If cardiovascular exercise is an important component of exercise - does it matter if it is treadmill walking, overground walking, biking, swimming etc.....Choosing the type of exercise the patient most enjoys will likely enhance adherence over time. 

Is 2 or 3 times a week of exercise just as effective as 5 times per week - we'll be more successful getting people to exercise 2 or 3 times per week rather than 5 times per week.

Does chronic exercise need to be delivered consistently over time or are "bouts" of exercise over a given number of weeks, a couple of times per year sufficient to achieve the desired result?

Is group treatment more effective than individual treatment to enhance adherence? In our experience implementing community exercise programs for people with PD, it is often easier for those with apathy or depression to "show up" at an appointment to exercise compared to exercising independently.  

Answers to these questions in addition to those posed by Lisa Shulman will advance our ability to use exercise as an effective tool to improve the lives of those with PD.