Introduction
Rationale and objective
Methods
Systematic review protocol
Eligibility criteria for study characteristics
Results
Study selection and synthesis
Study characteristics and results for pre-clinical studies
Authors | Study title | Subjects | Intervention |
---|---|---|---|
Goes et al., 2013 [21] | Neuroprotective effects of swimming training in a mouse model of Parkinson’s disease induced by 6-hydroxydopamine | • 2 groups (n = 20 each): 6-OHDA, saline | • 20–60 min/day, 5 days/week for 4 weeks |
• 2 treatment cohorts (n = 10 each): swimming training, no exercise | |||
• Starting 4 days after toxin administration | |||
Gorton et al., 2010 [17] | Exercise effects on motor and affective behavior and catecholamine neurochemistry in the MPTP-lesioned mouse | • 2 groups (n = 24 each): MPTP, saline | • Up to 1 hr/day, 5 days/week for 4 weeks |
• 3 treatment cohorts (n = 8/group): forced exercise, voluntary exercise, no exercise | |||
• Starting 5 days after toxin administration | |||
Tajiri et al., 2010 [18] | Exercise exerts neuroprotective effects on Parkinson's disease model of rats | • 1 group (n = 60): 6-OHDA | • 30 min/day, 5 days/week for 4 weeks |
• 2 treatment cohorts (n = 30 each): forced exercise, no exercise | |||
• Starting 1 day after toxin administration | |||
Aguiar et al., 2009 [19] | Physical exercise improves motor and short-term social memory deficits in reserpinized rats | • 4 groups (n = 24 each): high/low dose reserpine or high/low dose saline | • 20–25 min/day, 5 days/week for 4 weeks |
• Starting 4 weeks before toxin administration | |||
• 3 treatment cohorts± (n = 8/group):forced exercise, voluntary exercise, no exercise | |||
Pothakos et al., 2009 [20] | Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson's disease with severe neurodegeneration | • 2 groups (n = 29 each): probenecid/MPTP (model of chronic PD), probenecid only | • 40 min/day, 5 days/week for 8–12 weeks |
• Starting 1 week before, 5 weeks during, 8–12 weeks after toxin administration | |||
• 2 treatment cohorts (n = 5-10/group): forced endurance exercise, no exercise – for probenicid/MPTP group only | |||
Fisher et al., 2004 [16] | Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- lesioned mouse basal ganglia | • 2 groups (n = 60 each): MPTP, saline | • Up to 2x 30 min/day, 5 days/week for 4 weeks |
• 2 treatment cohorts (n = 20/group): forced exercise, no exercise* | |||
• Starting 4 days after toxin administration |
Study | Behavioral outcomes | Neurobiological outcomes | Major sources of risk of bias |
---|---|---|---|
Goes et al., 2013 [21] |
Forced exercise following onset of experimental PD:
|
Changes in the striatum from forced exercise following onset of experimental PD:
| Performance bias: sedentary control animals were not exposed to the swimming training program, the warm water or handled to be dried off following each session. |
• Decreased marker of depression (tail suspension) | • Decreased interleukin 1-beta levels (proinflammatory cytokines) | ||
• Improved motor coordination (decreased falls on Rotarod test) | • Attenuated inhibition of glutathione peroxidase activity, decreased glutathione reductase and glutathione S-transferase activity (all markers of oxidative stress) | ||
• Improved long-term memory, but not short-term memory in object recognition test | |||
• Increased dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid levels | |||
Gorton et al., 2010 [17] |
Forced and voluntary exercise following onset of experimental PD:
|
Forced and voluntary exercise following onset of experimental PD:
| Performance bias: each animal was only evaluated on one test. |
• Improved motor learning (Rotarod) | • Had no effect on levels of DA in the striatum and serotonin in the amygdala compared to saline controls | ||
• Reduced anxiety in elevated plus maze (passive avoidance task, authors linked to cognition/memory) | |||
• Forced and voluntary exercise increased DA in the striatum to similar levels following MPTP or saline administration | |||
• Had no effect on markers of depression, sucrose preference and tail suspension (MPTP lesion also had no effect) | |||
• Forced exercise increased 5HT in the nucleus accumbens in MPTP-treated mice compared to saline controls | |||
Tajiri et al., 2010 [18] |
Exercise following onset of experimental PD:
|
Exercise following onset of experimental PD:
| Information bias: exercise was started soon (24 hrs) after toxin administration, so the lesion may not represent a complete PD-like model. |
• Improved cylinder test, amphetamine-induced rotational test (authors linked to cognitive-related behavior) | • Preserved nigrostriatal dopamine neurons (increased tyrosine hydroxylase-positive fibers) | ||
• Increased migration of new-born neural stem/progenitor cells toward striatum | |||
• Up-regulated neurotrophic factors, BDNF and GDNF, in the striatum | |||
Aguiar et al., 2009 [19] |
Forced and voluntary exercise before onset of experimental PD:
| Neurobiological outcomes not assessed | Information bias: behavioral testing was soon (24 hrs) after the reserpine administration, so the lesion may not represent a complete PD-like model. |
• Improved motor deficits following a high dose of reserpine | |||
• Improved short-term social memory (tested through olfactory discrimination), with no deficit on motor or olfactory function from the low dose of reserpine | |||
Pothakos et al., 2009 [20] | Endurance exercise before and following onset of experimental chronic PD: |
Endurance exercise before and after onset of experimental chronic PD:
| Selection biases: there was not a group that received exercise and probenecid. There was also not a control group with only a saline injection. The effects of the control solution, probenecid, on cognition are not known. |
• Reversed balance and gait performance, restored regular movement | • Did not raise striatal DA (n = 6) | ||
• Did not reverse loss of tyrosine-hydroxylase fibers in substantia nigra (pars compacta) | |||
• Had no effect on learning (cued Morris water maze), amphetamine-stimulated locomotion or motor coordination | |||
Fisher et al., 2004 [16] |
Exercise following onset of experimental PD:
|
Exercise following onset of experimental PD:
| Information bias: the learning paradigm for behavioral results (learning to stay on the treadmill) relied substantially on motor capacity. |
• Improved velocity and endurance on treadmill | • Had no effect on tyrosine hydroxylase | ||
• Sensory feedback not needed over time for behavioral response (i.e., maintaining a forward position on treadmill), authors suggested indicative of learning | • Up-regulated dopamine D2 receptor mRNA expression | ||
• Down-regulated striatal DAT | |||
• Reversed increased nerve terminal glutamate in striatum (as a result of MPTP) |
Major sources of risk of bias for pre-clinical studies
Study characteristics and results for clinical studies
Study
|
Can exercise improve a marker of cognitive function?
|
Quality of evidence
2
|
Strength of recommendation
3
|
---|---|---|---|
Studies that specifically measured executive function (n = 4)
| |||
McKee et al. 2013 [29] | Yes | Moderate | Strong |
Cruise et al. 2011 [26] | Yes | Moderate | Strong |
Ridgel et al. 2011 [28] | Yes | Moderate | Strong |
Tanaka et al. 2009 [27] | Yes | Moderate | Strong |
Studies that measured unspecified aspects of cognition (n = 4)
| |||
Dos Santos Mendes et al. 2012 [25] | Yes | Low | Weak |
Pompeu et al. 2012 [24] | Yes | Low | Weak |
Müller et al. 2010 [23] | Yes | Low | Weak |
Baatile et al. 2000 [22] | Yes | Low | Weak |
Authors | Study title | Subjects | Intervention | Study design |
---|---|---|---|---|
Studies that specifically measured executive function (n = 4)
| ||||
McKee et al. 2013 [29] | The Effects of Adapted Tango on Spatial Cognition and Disease Severity in Parkinson’s Disease | Total n = 33 PD | • Tango or education lessons | Randomized controlled trial |
• n = 15 tango | • Sessions 90 minutes long, 20 sessions over 12 weeks, follow-up after 10–12 weeks | |||
• n = 13 control | ||||
Cruise et al. 2011 [26] | Exercise and Parkinson's: benefits for cognition and quality of life | Total n = 28 PD | • Moderate-to-high-intensity anabolic and aerobic exercise or usual care | Single-blind randomized controlled trial |
• n = 15 exercise | ||||
• n = 13 control | • Sessions 1 hr/day, 2x/week for 12 weeks | |||
Ridgel et al. 2011 [28] | Changes in executive function after acute bouts of passive cycling in Parkinson's disease | Total n = 19 PD | • Low-intensity passive aerobic exercise (cycling) | Randomized controlled trial, cross-over |
• Sessions 1/week for 4 weeks | ||||
Tanaka et al. 2009 [27] | Benefits of physical exercise on executive functions in older people with Parkinson's disease | Total n = 20 PD | • Moderate-intensity multimodal exercise training (aerobic, resistance, coordination and balance) or usual care | Controlled trial* |
• n = 10 exercise | ||||
• n = 10 control | ||||
• Sessions 1 hr/day, 3x/week for 24 weeks, intensity increased every 4 weeks | ||||
Studies that measured unspecified aspects of cognition (n = 4)
| ||||
Dos Santos Mendes et al. 2012 [25] | Motor learning, retention and transfer after virtual-reality-based training in Parkinson's disease - effect of motor and cognitive demands of games: a longitudinal, controlled clinical study | Total n = 27 | • Low-intensity Wii FitTM training, involving motor shifts and cognitive skills | Longitudinal pre-post trial |
• n = 16 PD | ||||
• n = 11 healthy control | • Sessions 1 hr/day, 2x/week for 7 weeks, follow-up at 60 days | |||
Pompeu et al. 2012 [24] | Effect of Nintendo WiiTM-based motor and cognitive training on activities of daily living in patients with Parkinson's disease: A randomised clinical trial | Total n = 32 PD | • Both groups: low-intensity stretching, strengthening | Single-blind randomized controlled trial |
• n = 16 exercise & Wii | ||||
• Experimental group: Wii FitTM -based motor/cognitive training | ||||
• n = 16 exercise no Wii | ||||
Control group: balance exercises without feedback or cognitive stimulation | ||||
• Sessions 1 hr/day, 2x/wk for 7 weeks, follow-up at 60 days | ||||
Müller et al. 2010 [23] | Effect of exercise on reactivity and motor behaviour in patients with Parkinson's disease | Total n = 22 PD | • Single bout of high-intensity endurance aerobic exercise (heart rate-targeted cycling) or rest following L-dopa administration | Randomized controlled feasibility trial, cross-over |
• Randomized order 1 day apart | ||||
Baatile et al. 2000 [22] | Effect of exercise on perceived quality of life of individuals with Parkinson's disease | Total n = 6 PD | • Low-intensity aerobic exercise program with Nordic walking poles (PoleStriding) | Nonrandomized feasibility trial, no control |
• Sessions 3x/week for 8 weeks |
Study | Behavioral outcomes | Major sources of risk of bias |
---|---|---|
Studies that specifically measured executive function (n = 4)
| ||
McKee et al. 2013 [29] | • Tango improved disease severity (UPDRS-III) and spatial cognition/mental imagery (Brooks Spatial Task) more than education group, maintained gains 10–12 weeks post-intervention | • Detection bias: study was underpowered (n = 23 tango, n = 8 education) to evaluate some main effects within groups, so main effect of time was evaluated |
Cruise et al. 2011 [26] | • Exercise improved verbal fluency and spatial working memory on Cambridge Neuropsychological Test Automated Battery | • Selection bias: the control group received usual care, no control for the effect of social interaction with exercise |
• Exercise was of “possible benefit” on semantic fluency and mood | • Information bias: the variable intensity level of the intervention could have affected outcomes | |
• Exercise did not benefit spatial or pattern recognition, quality of life, had no negative impact | ||
Ridgel et al. 2011 [28] | • Time to complete Trail Making Test A & B (tests executive function) decreased after passive cycling | • Selection bias: no control |
• Information bias: the same test pattern was used pre- and post-intervention, although practice effects were attempted to be controlled through pre-test training with the task | ||
• Performance improved on Trail Making Test B following passive cycling | ||
Tanaka et al. 2009 [27] | • Exercise improved executive function for “Categories Completed” (i.e., capacity for abstraction) and “Preservative Errors” (i.e., mental flexibility) on the Wisconsin Card Sorting Task | • Selection bias: small sample size, no long-term follow-up, not purely randomized |
•Information bias: no mention of medication administration; only one participant in the group had a heart rate monitor, so the intensity was targeted towards the group and not the individual | ||
• No interactions for confounding variables: concentrated attention, trait or state anxiety, depression | ||
Studies that measured unspecified aspects of cognition (n = 4)
| ||
Dos Santos Mendes et al. 2012 [25] | • PD showed no deficit in learning or retention on 7/10 games, deficits related to cognitive demands of tasks | • Selection bias: the baseline physical fitness of the subjects was not compared |
• PD had worse performance than healthy individuals on 5 tests | • Performance bias: no PD controls not performing intervention, no control for enjoyment or motivation | |
• PD could transfer learning to an untrained motor task at follow-up | ||
Pompeu et al. 2012 [24] | • Both groups improved UPDRS-II, MoCA and balance, no additional advantage from Wii FitTM | • Information bias: the baseline physical fitness of the subjects was not compared, so potential for differences between groups |
• Improved scores on Wii FitTM games, maintained at follow-up | ||
• No differences in outcomes between groups pre- to post-intervention or in follow-up | ||
Müller et al. 2010 [23] | • Reaction time increased after rest and decreased after exercise, movement time decreased after exercise | • Selection bias: no PD control group, no healthy controls |
• Information bias: one-day washout period (24 hours) may not have been long enough; pilot trial | ||
• Number of correct answers decreased after rest | ||
• Tapping rate increased after exercise | • Detection bias: unclear how reactivity was measured | |
• Peg insertion interval time decreased after exercise (complex movement sequences, visual and spatial cognition, sorting and planning) | ||
Baatile et al. 2000 [22] | • Improved UPDRS score (only total score significant) | • Selection bias: limited sample size, no control group; pilot trial |
• Improved PDQ-39 score, most improved in cognition component | • Information bias: exercise intensity not standardized |