Table 2.
Studies Comparing the Effect of Exercise vs Exercise of a Different Type and/or Dose on Outcomes Indicative of Parkinson’s Disease Progression. Studies Are Organized by Outcome Measures.
| Study | Participants † | Intervention group 1 | Intervention group 2 | Between group differences ‡ |
|---|---|---|---|---|
| Clinical outcomes (“off” MDS/UPDRS scores) | ||||
| Beck et al. (2018)61,b | n = 47 (39) Age: 70.8 ± 8.9 Sex (M/F): 31/8 PD duration: 6.9 ± 4.6 Disease severity (off): MDS-UPDRS-III 31.4 ± 10.9 |
Multimodal exercise: Walking, balance, stretching, and coordination exercises, with external focus of attention 60 min × 3/wk × 11 wk |
Multimodal exercise: Walking, balance, stretching, and coordination exercises, with internal focus of attention 60 min × 3/wk × 11 wk |
UPDRS “off” - Reduced UPDRS-III scores at 6 and 24 mo |
| Corcos et al. (2013) 44 | n = 48 Age: 58.8 ± 5.1 Sex (M/F): 28/20 PD duration: 6.5 ± 4.4 Disease severity (off): HY 2.3 ± 0.5, UPDRS-III 34.6 ± 11.7 |
Strength exercise: Alternating bimonthly between 3 sets of 8 or 2 sets of 12 for 11 upper (30%-40% 1RM) and lower (50%-60% 1RM) limb muscle groups 75 min × 2/wk × 104 wk |
Multimodal exercise: Balance exercise, low intensity strength training, stretching 75 min × 2/wk × 104 wk |
UPDRS “off” - No difference in the reduction in UPDRS-III scores at 6 mo - Reduced UPDRS-III scores at 12, 18, and 24 mo |
| Dibble et al. (2015) 45 | n = 41 Age: 68.4 ± 12.2 Sex (M/F): 25/16 PD duration: 6.8 ± 4.4 Disease severity (off): UPDRS-III 25.0 ± 9.2 |
Multimodal exercise: Strength and fitness training at RPE of 13 (ie, “somewhat hard”), and lower limb eccentric resistance training 60 min × 2/wk × 12 wk |
Multimodal exercise: Strength and fitness training at RPE of 13 (ie, “somewhat hard”) 60 min × 2/wk × 12 wk |
UPDRS “off” - No difference in UPDRS-III scores at 6 mo |
| Jansen et al. (2021) 67 | n = 29 Age: 62.8 ± 9.8 Sex (M/F): 14/15 PD duration: 3.5 ± 4.5 Disease severity (off): HY 2.0 ± 0, MDS-UPDRS-III 34.5 ± 10.6 |
Aerobic exercise: Cycling (60%-80% heart rate reserve) at forced high cadence 55 min × 3/wk × 8 wk |
Aerobic exercise: Cycling (60%-80% heart rate reserve) at preferred cadence 55 min × 3/wk × 8 wk |
MDS-UPDRS “off” - No difference in reduced MDS-UPDRS-III scores at 8 wk |
| Perez de la Cruz (2017)51,b | n = 30 Age: 67.2 ± 7.9 Sex (M/F): 13/16 PD duration: 6.5 ± 2.9 Disease severity (off): HY 2.8 ± 0.7, UPDRS-III 15.2 ± 7.3 |
Aquatic exercise: Aquatic Ai Chi (includes balance and flexibility exercises) 45 min × 2/wk × 10 wk |
Multimodal exercise: Strength, aerobic, balance, and stretching exercises on land 45 min × 2/wk × 10 wk |
UPDRS “off” - Reduced UPDRS-III scores at 10 and 14 wk - Reduced UPDRS-total scores at 14 wk |
| Ridgel et al. (2009)52,b | n = 10 Age: 61.2 ± 6.0 Sex (M/F): 8/2 PD duration: 6.2 ± 5.7 Disease severity (off): UPDRS-III 48.7 ± 14.1 |
Aerobic exercise: Cycling at forced high cadence (30% faster than preferred cadence) 60 min × 3/wk × 8 wk |
Aerobic exercise: Cycling at preferred cadence 60 min × 3/wk × 8 wk |
UPDRS “off” - Reduced UPDRS-III scores at 8 wk |
| Schenkman et al. (2018)27,a | n = 88 Age: 63.5 ± 9.5 Sex (M/F): 49/39 PD duration: 0.5 ± 0.7 Disease severity (off): HY 1.7 ± 0.5, UPDRS-III 16.5 ± 7.0 |
Aerobic exercise: High intensity treadmill training (80%-85% heart rate maximum) 45 min × 4/wk × 26 wk |
Aerobic exercise: Moderate intensity treadmill training at (60%-65% heart rate maximum) 45 min × 4/wk × 26 wk |
UPDRS “off” - NR. Appears that there are no differences in UPDRS-III scores |
| Vivas et al. (2011)76,b | n = 12 Age: 67.0 ± 5.5 Sex (M/F): 7/5 PD duration: 6.0 ± 2.9 Disease severity (off): HY 2.5 ± 0.5, UPDRS-total 41.1 ± 12.7 |
Aquatic exercise: Trunk mobility, balance, and transfer training in the pool 45 min × 2/wk × 4 wk |
Multimodal exercise: Trunk mobility, balance, and transfer training on land 45 min × 2/wk × 4 wk |
UPDRS “off” - Reduced UPDRS-total scores at 1 mo |
| Xiao and Zhuang (2016)55,b | n = 96 Age: 67.3 ± 15.2 Sex (M/F): 67/29 PD duration: 5.8 ± 0.5 Disease severity (off): HY 2.2 ± 1.6, UPDRS-III 27.2 ± 15.9 |
Aerobic exercise: Walking 30 min × 7/wk × 26 wk |
Multimodal exercise: Qigong and walking Qigong: 45 min × 4/wk; Walking 30 min × 7/wk; x26 wk |
UPDRS “off” - Reduced UPDRS-III scores at 6 mo |
| Neurochemical outcomes (trophic factors, inflammatory markers, oxidative stress factors) | ||||
| Landers et al. (2019) 49 | n = 27 Age: 64.0 ± 8.9 Sex (M/F): 19/8 PD duration: 4.8 ± 4.6 Disease severity (off): HY 2 ± 0.4, MDS-UPDRS-III 36.4 ± 13.7 |
Multimodal exercise: Moderate to high intensity aerobic exercises (70%-80% estimated heart rate maximum), resistance exercises (50%-80% 1RM), balance exercises, and flexibility exercises. 90 min × 3-4/wk × 8 wk |
Multimodal exercise: Low to moderate intensity aerobic exercises (50%-65% estimated heart rate maximum), resistance exercises (<50% 1RM), balance exercises, and flexibility exercises. 60 min × 3-4/wk × 8 wk |
Trophic factor - No difference in BDNF at 8 wk and at 6-mo follow-up. - BDNF concentration returned to baseline levels in both groups at 6-mo follow-up. Inflammatory markers - No differences in anti-inflammatory cytokines (IL10, IL10: TNF-α, IL6) at 8 wk and at 6-mo follow-up. - No differences in pro-inflammatory cytokines (TNF-α) 8 wk and at 6-mo follow-up. - All anti-inflammatory cytokines returned to baseline levels, whereas pro-inflammatory cytokines (TNF-α) continued to increase to a higher level in both groups at 6-mo follow-up. Oxidative stress - No differences in the concentration of antioxidative factor (SOD1) at 8 wk and at 6-mo follow-up. - Antioxidative factor (SOD1) returned to baseline levels in both groups at 6-mo follow-up. |
| Li et al. (2022)77,a | n = 63 (54) Age: 62.3 ± 5.6 Sex (M/F): 39/24 PD duration: 4.9 ± 3.2 Disease severity (on): HY 1.9 ± 0.5, UPDRS-III 21.4 ± 10.2 |
Balance exercise: Tai Chi 60 min × 2/wk × 52 wk |
Aerobic exercise: Brisk walking (50%-60% heart rate maximum) 60 min × 2/wk × 52 wk |
Trophic factor - No difference in VEGF, basic FGF, or PDGF-BB Inflammatory markers - No difference in most pro-inflammatory (TNF-α, 93% of interleukins) or anti-inflammatory cytokines - A few pro-inflammatory markers were downregulated (7% of interleukins, MCP-1, MIP-1a) - Two anti-inflammatory markers (GM-CSF, eotaxin) were upregulated |
| Sajatovic et al. (2017)34,b | n = 30 Sex (M/F): 19/11 Age: 70.0 ± 7.9 PD duration: 6.8 ± 5.3 Disease severity (on): HY 2.5 ± 0.7 MDS-UPDRS-III 33.8 ± 9.1 |
Multimodal exercise: Aerobic and resistance exercises with supervision 40 min × 3/wk × 24 wk |
Multimodal exercise: Written instruction for the same aerobic and resistance exercises as Intervention-1, performed without supervision 40 min × 3/wk × 24 wk |
Trophic factor - No differences in BDNF concentration at 12 wk (midway through intervention) or 24 wk. Inflammatory markers - No differences in pro-inflammatory cytokines (TNF-α), and anti-inflammatory cytokines (IL-6) at 12 wk (midway through intervention) and 24 wk. |
| Soke et al. (2021) 72 | n = 40 (29) Age: 57.6 ± 8.6 Sex (M/F): 19/10 PD duration: 7.9 ± 4.4 Disease severity (off): HY 2.3 ± 0.5, UPDRS-III 31.2 ± 11.3 |
Multimodal exercise: Treadmill training (60%-80% heart rate maximum) and task-oriented circuit training 83 min × 3/wk × 8 wk |
Aerobic exercise: Treadmill training (60%-80% heart rate maximum) 30 min × 3/wk × 8 wk |
Trophic factors - No differences in BDNF, GDNF, IGF-1, or VEGF concentrations Inflammatory markers - No differences in pro-inflammatory cytokines (TNF-α) and anti-inflammatory cytokines (IL-1b) |
| Neuroimaging outcomes (brain structure, volume, activation and functional connectivity, dopamine receptor binding) | ||||
| Droby et al. (2020)65,c | n = 42 (37) Age: 73.2 ± 6.6 Sex (M/F): 22/15 PD duration: 9.0 ± 6.3 Disease severity (on): HY 2.5 ± 0.4, UPDRS-III 27.8 ± 12.4 |
Aerobic exercise: Treadmill training in virtual reality environment (dual tasking) at 80% of overground speed 45 min × 3/wk × 6 wk |
Aerobic exercise: Treadmill training without virtual reality at 80% of overground speed 45 min × 3/wk × 6 wk |
Brain connectivity (rs-fMRI: intra-network connectivity analysis) - Improved functional connectivity in the sensorimotor and cerebellar networks (ie, improved attentional resource allocation for maintaining automated motor sequences) - No difference in functional connectivity in the dorsal attention, lateral motor, executive control, salience, frontostriatal, or basal ganglia networks (ie, no change in gait control via higher motor and cognitive pathways which bypass the striatum, or in the striatum itself) |
| Hajebrahimi et al. (2022) 57 | n = 30 (24) Age: 65.9 ± 9.1 Sex (M/F): 19/5 PD duration: NR Disease severity (on): UPDRS-III 14.5 ± 8.2 |
Multimodal exercise: Balance and leg strengthening exercises using Nintendo Wii™ 60 min × 3/wk × 4 wk |
Multimodal exercise: Stretching, balance and leg strengthening exercises 60 min × 3/wk × 4 wk |
Brain connectivity (rs-fMRI: intra-network connectivity analysis) - Increased activation of precuneus in the DMN network |
| Kim et al. (2022) 58 | n = 44 Age: 68.1 ± 8.2 Sex (M/F): 13/31 PD duration: 9.0 ± 5.2 Disease severity (on): HY 3.0 ± 0, MDS-UPDRS-III 36.6 ± 11.9 |
Aerobic exercise: Treadmill walking with exoskeleton, auditory cues and feedback on performance 45 min × 3/wk × 4 wk |
Aerobic exercise: Treadmill walking 45 min × 3/wk × 4 wk |
Brain connectivity (rs-fMRI: intra-network and inter-network connectivity analysis) - Increased activation of the precuneus within the default mode network (intra-network) - Decreased coupling between the visual and dorsal attention, the bilateral central executive, and the auditory and medial temporal, networks (ie, less reliance on compensatory attentional pathways) (inter-networks analysis) |
| Maidan et al. (2018)69,b,c | n = 64 Sex (M/F): 45/19 Age: 71.7 ± 1.2 PD duration: 9.3 ± 1.1 Disease severity (on): UPDRS-III 33.2 ± 2.6 |
Aerobic exercise: Treadmill training in virtual reality environment (dual tasking) at 80% of overground speed 45 min × 3/wk × 6 wk |
Aerobic exercise: Treadmill training without virtual reality at 80% of overground speed 45 min × 3/wk × 6 wk |
Brain activation (fNIRS: activation detection) - Improved cortical inhibition in the right prefrontal cortex (ie, improved automaticity). - No differences in cortical inhibition in the left prefrontal cortex. |
| Maidan et al. (2017)70,c | n = 34 Age: 71.4 ± 1.6 Sex (M/F): 23/11 PD duration: 9.8 ± 1.5 Disease severity (on): MDS-UPDRS-III 28.9 ± 3.5 |
Aerobic exercise: Treadmill training in virtual reality environment (dual tasking) at 80% of overground speed 45 min × 3/wk × 6 wk |
Aerobic exercise: Treadmill training without virtual reality at 80% of overground speed 45 min × 3/wk × 6 wk |
Brain activation (t-fMRI: activation detection) - Reduced activation of right Brodmann area 10 and inferior frontal gyrus (ie, increased efficiency of cognitive networks) - Greater activation of left anterior cerebellum and middle temporal gyrus (ie, worse sensory integration for gait control) |
| Shah et al. (2016) 78 | n = 27 Age: 56.9 ± 8.3 Sex (M/F): 17/10 PD duration: 3.7 ± 4.1 Disease severity (off): MDS-UPDRS-III 24.8 ± 9.8 |
Aerobic exercise: Cycling (60%-80% heart rate reserve) at forced high cadence 60 min × 3/wk × 8 wk |
Aerobic exercise: Cycling (60%-80% heart rate reserve) at preferred cadence 60 min × 3/wk × 8 wk |
Brain connectivity (t-fMRI and rs-fMRI: seed based connectivity analysis) - No difference in thalamus-cortical connectivity (ie, no change in sensory integration to modulate motor output) |
| Silva-Batista et al. (2020) 54 , Vieira-Yano et al. (2021)75,d | n = 40 (32) Age: 65.6 ± 9.8 Sex (M/F): 21/11 PD duration: 8.8 ± 4.8 Disease severity (on): HY 3.1 ± 0.4, UPDRS-III 48.7 ± 11.0 |
Multimodal exercise: Progressive resistance training (of 7 upper and lower limb muscle groups) performed on unstable surfaces 85 min × 3/wk × 12 wk |
Multimodal exercise: Gait and balance training, resistance training with free weights, stretching 85 min × 3/wk × 12 wk |
Brain activation (t-fMRI: activation detection) - Increased BOLD activation of right middle-inferior temporal gyrus, mesencephalic locomotor region (which correlated to reduced NFOG-Q scores) and cerebellar locomotor region (ie, increased compensation for lack of gait automaticity) - No difference in SMA activation - Increased activation of right cerebellar locomotor region (which correlated to improved automaticity of stride length) |
| Neurophysiological outcomes (cortical inhibition, muscle activation patterns underlying bradykinesia) | ||||
| Calabrò et al. (2019)41,b | n = 50 Age: 71.5 ± 8 Sex (M/F): NR PD duration: 9.7 ± 3 Disease severity (on): UPDRS-III 30 ± 4 |
Multimodal exercise: Treadmill walking with auditory cues, overground gait, daily activity, and biomechanical training 195 min × 5/wk × 8 wk |
Multimodal exercise: Treadmill walking without auditory cues, overground gait, daily activity, and biomechanical training 195 min × 5/wk × 8 wk |
Cortical synchrony (EEG) - Improved ERS and ERD during gait (ie, greater cortical synchrony) - Increased TRCoh estimations (ie, greater inter-regional cortical connectivity) |
| Cheng et al. (2018)42,a,b | n = 18 Sex (M/F): 14/4 Age: 67.7 ± 7.8 PD duration: 5.8 ± 2.8 Disease severity (on): HY 1.4 ± 0.4 |
Aerobic exercise [a]: High intensity treadmill walking at RPE 14-15 (ie, “hard”), and overground walking training Multimodal exercise [b]: High intensity balance and strengthening exercises at RPE 14-15 (ie, “hard”), and overground walking training 40 min × 2-3/wk × 5 wk |
Multimodal exercise: Seated upper limb resistance exercise and overground walking training 40 min × 2-3/wk × 5 wk |
Cortical synchrony (EEG) - Improved β-ERD (ie, reduced cortical desynchrony) - No difference in α-ERD Cortical synchrony (EEG) - Improved β-ERD (ie, reduced cortical desynchrony) - No difference in α-ERD Cortical synchrony (EEG; [a] vs [b]) - [a vs b] No difference in β-ERD or α-ERD |
| David et al. (2016) 62 | n = 48 Age: 58.8 ± 5.1 Sex (M/F): 28/20 PD duration: 6.5 ± 4.4 Disease severity (off): HY 2.3 ± 0.5, UPDRS-III 34.6 ± 11.7 |
Strength exercise: Progressive resistance training: alternating bimonthly between 3 sets of 8 or 2 sets of 12 for 11 upper (30%-40% 1RM) and lower (50%-60% 1RM) limb muscle groups 75 min × 2/wk × 104 wk |
Multimodal exercise: Balance exercise, low intensity strength training, stretching 75 min × 2/wk × 104 wk |
EMG measures of bradykinesia - Increased peak velocity, increased first agonist burst duration and magnitude, and fewer agonist bursts prior to peak velocity (ie, improved bradykinesia) - No difference in antagonist burst magnitude |
| Fisher et al. (2008)6,a | n = 20 Age: 62.8 ± 12.4 Sex (M/F): 11/9 PD duration: 1.0 ± 0.8 Disease severity (on): HY 1.9 ± 0.4; UPDRS-III 29.1 ± 9.5 |
Aerobic exercise: Moderate-high intensity treadmill training at (>3 METs and/or >75% age-adjusted heart rate maximum) 45 min × 3/wk × 8 wk |
Multimodal exercise: Low intensity flexibility, balance, resistance, and functional exercises at (≤3 METs and/or ≤50% age-adjusted heart rate maximum) 45 min × 3/wk × 8 wk |
Cortical inhibition (TMS with EMG-measured MEP) - Increased maximum CSP in both brain hemispheres (ie, greater cortical inhibition indicative of more normal cortical function) |
| Jansen et al. (2021) 67 | n = 29 Age: 62.8 ± 9.8 Sex (M/F): 14/15 PD duration: 3.5 ± 4.5 Disease severity (off): HY 2.0 ± 0, MDS-UPDRS-III 34.5 ± 10.6 |
Aerobic exercise: Cycling at (60%-80% heart rate reserve) at forced high cadence 55 min × 3/wk × 8 wk |
Aerobic exercise: Cycling at (60-80% heart rate reserve) at preferred cadence 55 min × 3/wk × 8 wk |
EMG measures of bradykinesia - Improved maximal rate of force production of the moving hand (ie, reduced bradykinesia) - Improvements in the maximal rate of force production disappeared at follow-up 2 mo later - No difference in grip force delay, load force delay or total task time (ie, no change in interlimb coordination) |
| Liu et al. (2022) 59 | n = 28 Age: 67.9 ± 6.6 Sex (M/F): 16/12 PD duration: 6.9 ± 5.2 Disease severity (on): HY 1.8 ± 0.7, UPDRS-III 26.0 ± 10.9 |
Balance exercise: Square stepping in a smooth pattern 60 min x2/wk × 8 wk |
Multimodal exercise: Upper and lower limb strength training, postural education, and hand-eye coordination exercises 60 min x2/wk × 8 wk |
Cortical inhibition (TMS with EMG-measured MEP) - Increased maximum CSP (ie, greater cortical inhibition indicative of more normal cortical function) - Reduced SICI (ie, greater intracortical inhibition indicative of more normal function) |
| Marusiak et al. (2019) 50 | n = 20 Age: 73.0 ± 9.5 Sex (M/F): 9/11 PD duration: 8.5 ± 4.5 Disease severity (off): HY 2.3 ± 0.6 |
Multimodal exercise: Moderate intensity interval training on cycle ergometer (60%-75% heart rate maximum), and physiotherapy 60 min × 3/wk × 8 wk |
Multimodal exercise: Physiotherapy NR |
EMG measures of bradykinesia - Reduced muscle onset time, and increased rate of force development of the moving hand (ie, improved automatic adjustments) - Reduced delay between grip force development in both hands (ie, improved automatic bimanual coordination) |
| Pelosin et al. (2020)33,b,c | n = 24 Sex (M/F): 12/12 Age: 71.8 ± 3.6 PD duration: NR Disease severity (on): UPDRS-III 30.6 ± 10.3 |
Aerobic exercise: Treadmill training in virtual reality environment (dual tasking) at 80% of overground speed 45 min × 3/wk × 6 wk |
Aerobic exercise: Treadmill training without virtual reality at 80% of overground speed 45 min × 3/wk × 6 wk |
Cortical inhibition (TMS with EMG-measured MEP) - Improved cortical inhibition (greater SAI in M1 cortex) at 6 wk (ie, indicative of more normal cortical function) - No difference in cortical inhibition at 6-mo follow-up |
| Silva-Batista et al. (2017)71,a | n = 26 Age: 64.2 ± 9.9 Sex (M/F): 20/6 PD duration: 10.1 ± 4.0 Disease severity (on): HY 2.5 ± 0.5, UPDRS-III 44.4 ± 11.1 |
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 |
Strength exercise: 8-12 RM of 5 upper and lower limb muscle groups 50 min × 2/week × 12 wk |
EMG measures of bradykinesia - Increased presynaptic inhibition and disynaptic reciprocal inhibition (ie, improved muscle coordination), the latter to levels similar to healthy people |
Abbreviations: 1RM, 1-repetition maximum; BDNF, brain-derived neurotrophic factor; EEG, electroencephalography; EMG, electromyography; ERD, event-related desynchronization; ERS, event-related synchronization; fNIRS, functional near-infrared spectroscopy; HY, Hoehn and Yahr scale; IL-6, interleukin 6; IL-10, interleukin 10; MDS-UPDRS-III, Movement Disorder Society Unified Parkinson’s Disease Rating Scale motor section; NR, not reported; RPE, rating of perceived exertion; rs-fMRI, resting state functional magnetic resonance imaging; SAI in M1 cortex, short-latency afferent inhibition in primary motor cortex; SICI, short-interval intracortical inhibition; SMA, supplementary motor area; SOD, superoxide dismutase; t-fMRI, task-based functional magnetic resonance imaging; TNF-α, tumor necrosis factor-alpha; TRCoh, task-related coherence; UPDRS-III, Unified Parkinson’s Disease Rating Scale motor section.
†
n: number randomized. If participant characteristics were reported only for those who completed, this n was reported in brackets. Age and PD duration were measured in years. Values are reported as number, or mean ± SD.
‡
Changes indicate the effect of intervention group/s 1 relative to intervention group 2. If specific timepoints of outcome measures were not specified, the outcomes were measured upon completion of the intervention. Outcomes were measured at post-test upon completion of the intervention period, unless otherwise specified.
a
Studies with 3 groups. Study characteristics and results for the exercise vs exercise comparisons only are presented in this table; for all studies except 1, 42 the study characteristics were a subset of the entire study sample. If the study included a control group, study characteristics for the entire sample and results for exercise vs control comparisons were presented in Table 1.
b
Studies which did not specify exercise intensity.