Table 1.
Studies Comparing the Effect of Exercise vs Control (ie, No or Sham Exercise) on Outcomes Indicative of Parkinson’s Disease Progression. Studies Are Organized by Outcome Measures.
| Study | Participants † | Intervention group | Control group | Between group differences ‡ |
|---|---|---|---|---|
| Clinical outcomes (“off” MDS/UPDRS scores) | ||||
| Duncan and Earhart (2012) 46 | n = 62 Age: 69.9 ± 9.0 Sex (M/F): 35/27 PD duration: 6.1 ± 5.1 Disease severity (off): HY 2.6 ± 0.5, MDS-UPDRS-III 46.3 ± 10.5 |
Dance: Tango 60 min × 2/wk × 52 wk |
No exercise |
MDS-UPDRS “off” - Reduced MDS-UPDRS-III scores at 3, 6, and 12 mo |
| Duncan and Earhart (2014)66,d | n = 10 Age: 67.8 ± 9.1 Sex (M/F): 8/2 PD duration: 8.8 ± 6.0 Disease severity (off): HY 2.4 ± 0.4, MDS-UPDRS-III 48.4 ± 19.6 |
Dance: Tango 60 min × 2/wk × 104 wk |
No exercise |
MDS-UPDRS “off” - Reduced MDS-UPDRS-III scores at 12 and 24 mo |
| Frazzitta et al. (2015) 47 | n = 40 (31) Age: 68.5 ± 7.1 Sex (M/F): 21/19 PD duration: NR Disease severity (off): HY 1.2 ± 0.3, MDS-UPDRS-III 13.6 ± 4.6 |
Multimodal exercise: Multidisciplinary intensive rehabilitation (stretching, balance, gait, and aerobic treadmill training) 60 min × 10/wk × 8 wk |
No exercise |
UPDRS “off” - Reduced UPDRS-III scores at 6 and 24 mo |
| Jung et al. (2020),37,a Hasegawa et al. (2020)36,a,e | n = 93 (86) Age: 68.8 ± 7.6 Sex (M/F): 58/28 PD duration: 6.5 ± 5.0 Disease severity (off): HY 2.3 ± 0.5, MDS-UPDRS-III 42.3 ± 12.2 |
Multimodal exercise: Agility boot camp (gait training, strength training, functional exercises, Tai Chi, and boxing) 90 min × 3/wk × 6 wk |
No exercise |
MDS-UPDRS “off” - No difference in MDS-UPDRS-III scores |
| Schenkman et al. (2018) 27 | n = 128 Age: 63.6 ± 9.7 Sex (M/F): 73/55 PD duration: 0.5 ± 0.7 Disease severity (off): HY 1.7 ± 0.4, UPDRS-III 16.6 ± 7.0 |
Aerobic exercise: High intensity treadmill training (80%-85% heart rate maximum) Aerobic exercise: Moderate intensity treadmill training (60%-65% heart rate maximum) 45 min × 4/wk × 26 wk |
No exercise |
UPDRS “off” - Smaller increase in UPDRS-III scores at 6 mo UPDRS “off” - No difference in increased UPDRS-III scores at 6 mo |
| van der Kolk et al. (2019) 28 | n = 130 Age: 59.4 ± 8.8 Sex (M/F): 80/50 PD duration: 3.9 ± 4.2 Disease severity (off): HY 2.0 ± 0.2, MDS-UPDRS-III 28.4 ± 15.3 |
Aerobic exercise: Moderate-high intensity cycling (50%-80% heart rate reserve) 30-45 min × 3/wk × 26 wk |
Sham exercise: Stretching 30-45 min × 3/wk × 26 wk |
MDS-UPDRS “off” - Smaller increase in MDS-UPDRS-III scores at 6 mo |
| Vergara-Diaz et al. (2018)74,a | n = 32 Age: 63.9 ± 6.1 Sex (M/F): 16/16 PD duration: 2.9 ± 2.3 Disease severity (off): HY 2.2 ± 0.2, UPDRS-III 23.5 ± 9.2 |
Balance exercise: Tai Chi 55 min × 3/wk × 26 wk |
No exercise |
UPDRS “off” - Smaller increase in UPDRS-III scores at 6 mo |
| Neurochemical outcomes (trophic factors, inflammatory markers, oxidative stress factors) | ||||
| Bloomer et al. (2008)35,a,c | n = 16 Age: 59.0 ± 2.5 Sex (M/F): 8/8 PD duration: NR Disease severity (on): HY 1.5 ± 0.5 |
Strength exercise 2×/wk × 8 wk |
No exercise |
Oxidative stress (blood essay) - No differences in concentration of all antioxidative factors (GPx, SOD, catalase, TEAC) - Decreased concentration of oxidative factor (H2O2) |
| Cheung et al. (2018)43,a | n = 20 Age: 64.7 ± 7.6 Sex (M/F): NR PD duration: 4.8 ± 2.9 Disease severity (on): HY 2.0 ± 0.8; UPDRS-III 25.0 ± 7.0 |
Balance exercise: Hatha yoga 60 min × 2/wk × 12 wk |
No exercise |
Oxidative stress (blood essay) - No difference in concentration of antioxidative factors (catalase, SOD, GPX, GSH, GSH:GSSG ratio) - No difference in concentration of oxidative factors (MDA, protein carbonylation) |
| Dias Belchior et al. (2017)63,a | n = 22 (18) Age: 68.1 ± 11.7 Sex (M/F): 11/7 PD duration: 5.6 ± 4.1 Disease severity (off): HY 2.5 ± 0 |
Aerobic exercise: Treadmill gait training 30 min × 2/wk × 8 wk |
No exercise |
Trophic factor (blood essay) - No difference in serum BDNF concentration Oxidative stress (blood essay) - No difference in concentration of antioxidative factors (GSH) |
| DiFrancisco-Donoghue et al. (2012) 64 | n = 41 (36) Age: 68.0 ± 7.0 Sex (M/F): 20/17 PD duration: 8.2 ± 5.2 Disease severity (on): HY 2.0 ± 0 |
Multimodal exercise: Moderate-high intensity aerobic exercises (60%-70% VO2 max), and strength exercises (50%-80% 1RM) 40 min × 2/wk × 6 wk |
No exercise |
Oxidative stress (blood essay) - Increased concentration of antioxidative factors (GSH, and GSH:GSSG ratio) |
| Frazzitta et al. (2014) 8 | n = 25 (24) Age: 66.2 ± 4.6 Sex (M/F): NR PD duration: 8.0 ± 4.1 Disease severity (on): UPDRS-III 16.1 ± 3.0 |
Multimodal exercise: Low-moderate intensity aerobic treadmill exercises at (≤60% heart rate reserve), flexibility, balance and functional exercises. 60 min × 15/wk × 4 wk |
No exercise |
Trophic factor (blood essay) - Increased serum BDNF concentration |
| Freidle et al. (2022)56,d | n = 95 Age: 71.0 ± 6.1 Sex (M/F): 60/35 PD duration: 4.3 ± 5.7 Disease severity (on): HY 2.2 ± 0.4, MDS-UPDRS-III 31.5 ± 11.1 |
Balance exercise: Progressive balance training including dual-tasking 60 min × 2/wk × 10 wk |
No exercise |
Trophic factor (blood essay) - No difference in serum BDNF concentration |
| Li et al. (2022) 77 | n = 95 Age: 62.2 ± 6.0 Sex (M/F): 58/37 PD duration: 4.7 ± 2.9 Disease severity (on): HY 2.0 ± 0.4, UPDRS-III 20.7 ± 8.8 |
Balance exercise: Tai Chi Aerobic exercise: Brisk walking (50%-60% heart rate maximum) 60 min × 2/wk × 52 wk |
No exercise |
Trophic factor (blood essay) - Increased PDGF-BB - No difference in VEGF or basic FGF Inflammatory markers (blood essay) - No difference in most pro-inflammatory (TNF-α, and 71% of interleukins) or anti-inflammatory cytokines - Some pro-inflammatory markers were downregulated (29% of interleukins, MCP-1, MIP-1a, and MIP-1β) - One anti-inflammatory marker (GM-CSF) was upregulated Trophic factor (blood essay) - No difference in VEGF, basic FGF, or PDGF-BB Inflammatory markers (blood essay) - No difference in pro-inflammatory cytokines (TNF-α, interleukins, other factors) |
| O’Callaghan et al. (a) (2020)38,b | n = 32 (27) Sex (M/F): 17/10 Age: 67.4 ± 7.9 PD duration: NR Disease severity (on): HY 2.0 ± 0.2 |
Multimodal exercise: Moderate-high intensity aerobic and resistance exercises (60%-80% heart rate maximum) 45-60 min × 3/wk × 12 wk |
No exercise |
Trophic factor (blood essay) - No difference in serum BDNF concentration Inflammatory markers (blood essay) - Reduction in some pro-inflammatory cytokines |
| O’Callaghan et al. (b) (2020)38,b | n = 20 (17) Sex (M/F): 9/8 Age: 68.9 ± 7.3 PD duration: NR Disease severity (on): HY 2.3 ± 0.5 |
Strength exercise: High intensity interval power training (≥85% maximum heart rate) 45-60 min × 3/wk × 12 wk |
No exercise |
Trophic factor (blood essay) - Increased serum BDNF concentration |
| Szymura et al. (2020) 73 | n = 29 Sex (M/F): 19/10 Age: 65.7 ± 7.5 PD duration: NR Disease severity (on): HY 2.4 ± 0.5 |
Balance exercise: Moderate intensity balance training (60%-70% maximum heart rate) 60 min × 3/wk × 12 wk |
No exercise |
Trophic factor (blood essay) - Increased serum BDNF concentration - No between group differences in other circulating trophic factors (IGF-1, β-NGF) Inflammatory markers (blood essay) - Increased concentration of some anti-inflammatory cytokines (TGF-β1, fractalkine) - No difference in other anti-inflammatory cytokines (IL-6, IL-10, CD200) - No difference in pro-inflammatory cytokines (TNF-α) |
| Neuroimaging outcomes (brain structure, volume, activation and functional connectivity, dopamine receptor binding) | ||||
| Albrecht et al. (2021)60,d | n = 95 (65) Age: 70.4 ± 6.0 Sex (M/F): 40/25 PD duration: 5.1 ± 4.1 Disease severity (on): HY 2.2 ± 0.4, MDS-UPDRS-III 29.9 ± 12 |
Balance exercise: Progressive balance training including dual-tasking 60 min × 2/wk × 10 wk |
No exercise |
Brain structure (structural MRI: volume-based morphometry and structural covariance network analysis) - Increased connectivity between the bilateral thalami and right cerebellum in the structural covariance network Brain volume - No difference in gray matter volume |
| Fisher et al. (2013) 7 | n = 4 Age: 55.0 ± 4.0 Sex (M/F): 3/1 PD duration: NR Disease severity (off): UPDRS-III 15.0 ± 2.5 |
Aerobic exercise: Moderate-high intensity treadmill training at (>3 METs and/or >75% age-adjusted heart rate maximum) 60 min × 3/wk × 8 wk |
No exercise |
Dopamine receptor binding potential (PET scan) - Increased dopamine-D2 receptor binding potential |
| Freidle et al. (2022)56,d | n = 95 Age: 71.0 ± 6.1 Sex (M/F): 60/35 PD duration: 4.3 ± 5.7 Disease severity (on): HY 2.2 ± 0.4, MDS-UPDRS-III 31.5 ± 11.1 |
Balance exercise: Progressive balance training including dual-tasking 60 min × 2/wk × 10 wk |
No exercise |
Brain activation (t-fMRI: activation detection) - No difference in activation in the striatum, primary motor cortex, premotor cortex, supplementary motor area, anterior cingulate cortex, or dorsolateral prefrontal cortex |
| Johansson et al. (2022)48,d | n = 57 Age: 59.4 ± 9.6 Sex (M/F): 37/20 PD duration: 3.8 ± 3.0 Disease severity (off): MDS-UPDRS-III 28.3 ± 14.0 |
Aerobic exercise: Moderate-high intensity cycling (50%-80% heart rate reserve) 38 min × 3/wk × 26 wk |
Sham exercise: Stretching + relaxation 38 min × 3/wk × 26 wk |
Brain connectivity (rs-fMRI: [a] seed-based connectivity analysis, [b] intra-network connectivity analysis) - [a] Right corticostriatal-sensorimotor connectivity shifted anteriorly - [b] Improved right frontoparietal-dorsolateral prefrontal connectivity (ie, improved cognitive control) Brain volume and structure ([c] structural and [d] diffusion MRI) - [c] Reduced loss of global brain volume - [c] No change in localized gray matter volume - [d] No change in substantia nigra tissue integrity |
| King et al. (2020)68,a,d | n = 46 Age: 68.6 ± 7.5 Sex (M/F): NR PD duration: 8.4 ± 5.1 Disease severity (off): HY 2.5 ± 0.8, MDS-UPDRS-III 47.2 ± 13.0 |
Multimodal exercise: Agility boot camp (gait training, strength training, functional exercises, Tai Chi, and boxing) 80 min × 3/wk × 6 wk |
No exercise |
Brain connectivity (rs-fMRI: region to region connectivity analysis) - Reduced right pedunculopontine-supplementary motor area connectivity (ie, reduced maladaptive response associated with FOG) |
| Sacheli et al. (2019)53,c | n = 35 Age: 67.2 ± 7.2 Sex (M/F): 22/13 PD duration: 4.5 ± 3.5 Disease severity (off): MDS-UPDRS-III 24.6 ± 12.0 |
Aerobic exercise: High intensity cycling (60%-80% VO2 max) 50 min × 3/wk × 12 wk |
Sham exercise: Stretching 3×/wk × 12 wk |
Dopamine release (PET scan) - Increased dopamine release only in the caudate in the better hemisphere - No difference in dopamine release in the caudate of the worse hemisphere, or in the putamen of both hemispheres. Dopamine receptor binding potential (PET scan) - Increased D2/3 receptor availability in the middle and posterior putamen of both hemispheres. Brain activation (t-fMRI: activation detection) - Significant higher BOLD signal increment in the ventral striatum of both hemispheres when performing a reward task with 75% probability of winning (ie, increased responsivity of the mesolimbic reward pathways). |
| Neurophysiological outcomes (cortical inhibition, muscle activation patterns underlying bradykinesia) | ||||
| Fisher et al. (2008) 6 | n = 30 Age: 62.9 ± 12.1 Sex (M/F): 19/11 PD duration: 1.1 ± 0.9 Disease severity (on): HY 1.9 ± 0.4; UPDRS-III 28.6 ± 8.9 |
Aerobic exercise: Moderate-high intensity treadmill training (>3 METs and/or >75% age-adjusted heart rate maximum) Multimodal exercise: Low intensity flexibility, balance, resistance, and functional exercises (≤3 METs and/or ≤50% age-adjusted heart rate maximum) 45 min × 3/wk × 8 wk |
No exercise |
Cortical inhibition (TMS with EMG-measured MEP) - Increased maximum CSP in both brain hemispheres (ie, greater cortical inhibition indicative of more normal cortical function) Cortical inhibition (TMS with EMG-measured MEP) - No difference in maximum CSP in both brain hemispheres (ie, no change in cortical inhibition) |
| Silva-Batista et al. (2017) 71 | n = 37 Age: 64.5 ± 9.4 Sex (M/F): 29/8 PD duration: 10.2 ± 4.5 Disease severity (on): HY 2.5 ± 0.4, UPDRS-III 44.6 ± 10.3 |
Strength exercise: Progressive resistance training (8-12 RM of 5 upper and lower limb muscle groups) Multimodal exercise: Progressive resistance training (8-12 RM of 5 upper and lower limb muscle groups) performed on unstable surfaces 50 min × 2/wk × 12 wk |
No exercise |
EMG measures of bradykinesia - Increased presynaptic inhibition (ie, reduced bradykinesia) - No change in disynaptic reciprocal inhibition (ie, no change in rigidity) EMG measures of bradykinesia - Increased presynaptic inhibition and disynaptic reciprocal inhibition (ie, improved muscle coordination), to levels similar to healthy people |
Abbreviations: BDNF, brain-derived neurotrophic factor; β-NGF, beta nerve growth factor; CD200, cluster of differentiation-200; CSP, cortical silent period; EMG, electromyography; FGF, fibroblast growth factor; GM-CSF, granulocyte macrophage colony stimulating factor; GPX, glutathione peroxidase; GSH, glutathione; GSH:GSSG ratio, glutathione and oxidized glutathione ratio; H2O2, hydrogen peroxide; HY, Hoehn and Yahr scale; IGF-1, insulin-like growth factor 1; IL-6, interleukin 6; IL-10, interleukin 10; MDA, malondialdehyde; MDS-UPDRS-III, Movement Disorder Society Unified Parkinson’s Disease Rating Scale motor section; MEP, motor evoked potential; MET, metabolic equivalent; NR, not reported; PDGF-BB, platelet derived growth factor BB; PET, positron emitted tomography; rs-fMRI, resting state functional magnetic resonance imaging; SOD, superoxide dismutase; t-fMRI, task-based functional magnetic resonance imaging; TEAC, trolox equivalent antioxidant capacity; TGF-β1, transforming growth factor beta 1; TMS, transcranial magnetic stimulation; TNF-α, tumor necrosis factor alpha; UPDRS-III, Unified Parkinson’s Disease Rating Scale motor section; VEGF, vascular endothelial growth factor.
†
n: number randomized. If participant characteristics are reported only for those who completed, this n is reported in brackets. Age and PD duration were measured in years. Values are reported as number, or mean ± SD.
‡
Changes indicate the effect of exercise for the intervention group/s relative to the control group. Outcomes were measured at post-test upon completion of the intervention period, unless otherwise specified.
a
Studies which did not specify exercise intensity.
b
Two trials were reported in O’Callaghan et al. 38 Each trial was conducted at different time points with different groups of PD participants.
c
Studies which did not report session duration for the intervention and/or control group/s.