EXERCISE IN PARKINSON'S DISEASE: WHAT DOES THE DATA TELL US ABOUT NEUROPROTECTION AND NEURORESTORATION?

Christina MarciniakThe Rehabilitation Institute of Chicago and Northwestern University

AAPMR November 2014

DISCLOSURES

I have no relevant disclosures.

DISCLOSURES

OBJECTIVES

Discuss preclinical evidence for exercise as neuro-protection in PD

Review retrospective human studies suggesting exercise is neuro-protective in PD

Discuss human studies evaluating exercise effects in neuro-restoration in PD

CUMULATIVE RCT/CCTS OF PHYSICAL THERAPY IN PD

Cumulative number of randomized and controlled clinical trials on the efficacy of physical therapy in PD Parkinson Disease

Keus et al. Physical Therapy in Parkinson’s Disease: Evolution and Future Challenges.2009;Movement Disorders:24(1)

EXERCISE PROTECTS AGAINST TOXIN INDUCED PD IN ANIMAL MODELS.

Petzinger GM et al. Effects of treadmill exercise on dopaminergic transmission in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury. L Neurosci 2007; 27:5291-300.

DURATION/INTENSITY OF EXERCISE DETERMINE TOXIN EFFECTS.

3 months of exercise, but not 1 or 2 months prior to MPTP administration provided complete protection from DA loss in mice.Protein changes related to energy regulation, cellular

metabolism, cytoskeleton, intracellular signaling even Gerecke. Brain Research 2010

Mice running unrestricted, but limited in distance or time lost DA cells

Faherty. Brain Research 2005

EXERCISE ELEVATES DOPAMINE D2 RECEPTOR IN A MOUSE MODEL OF PARKINSON'S DISEASE. IN VIVO

DEC 15;25(16):2777-84N CALIFORNIA, LOS ANGELES, CALIFORNIA, USA.

Marta G. Vučković, et al. Movement Disorders. 2010 December 15;25(16):2777-2784.

EXERCISE RESULTS IN ENHANCED CONNECTIVITY

EXERCISE APPEARS NEUROPROTECTIVE IN RETROSPECTIVE HUMAN STUDIES.

Moderate or vigorous levels of physical activity are associated with lower risk of developing PDChen H et al. Physical activity and the risk of Parkinson’s disease. Neurology

2005; 64:664-9.

Regular exercise delays the appearance of parkinsonian features in persons already diagnosed with PD.

Tsia CH et al. Environmental risk factors of young-onset Parkinson’s disease: a case-control study: Clin Neurol Neurosurg 2002;104:328-33

Xu, Q. et al. Neurology 2010;75:341-348

Exercise throughout adulthood decreases PD.

Odds Ratio 0.40

PARKINSON’S AND EXERCISE

After diagnosis, persons with PD decrease their physical activity levels. Only 12-15% are referred to physiotherapy.

Thacker EL et al. Recreational physical activity and risk of Parkinson’s disease. Movement Disorders

2008; 23:69-74

Only 7-57% report being treated by a physical therapist, though there are large differences in utilization.

Nijkrake MJ et al. Allied healthcare in Parkinson’s disease: referral, consultation, and professional expertise. Movement Disorders 2009; 24:282-6.

High Intensity exercise can normalize Corticomotor excitability in early PD

Fisher, Archives PMR 2008

Subjects with PD Hoehn and Yahr Stage 1-2 randomized to 3 groupsZero intensity exercise (education)Low intensity exercise (50%) – 24 sessions over 8 weeksHigh intensity exercise (75%)– 24 treadmill training over 8 weeks

High-intensity group subjects:Clinical outcomes: Post-exercise increases in:

Increases in gait speed, step and strike lengthHip and ankle joint excursion during self-selected fast gait Improved weight distribution during sit-to stand tasks

Outcome: Corticomotor excitability measured by Transcutaneous Mag Stim Silent Period

Neurorestoration: Are thereExercise effects in PD patients?

Cortical Silent Period effects With High intensity exercise

FORCED EXERCISE AND PD: RATE VS RESISTANCE

Tandem bike used to force patients to exercise 30 % greater than preferred rate

Control group exercised at preferred rate

Ridgel, Neurorehab and Neural Repair 2009

Jay L. Alberts, Susan M. Linder, Amanda L. Penko, Mark J. Lowe1, Micheal Phillip Exerc Sport Sci Rev. 2011;39(4):177-186. 

“FORCED” EXERCISE IMPROVED PD MOTOR SCORE ON THE UPDRS.

BOTH GROUPS IMPROVED THEIR AEROBIC CONDITIONING

“FORCED” CYCLING IMPROVES HAND FXN

THREE HOURS OF AEROBIC EXERCISE/DAY INCREASES BDNF IN PERSONS WITH PD

NATIONAL PARKINSON FOUNDATION DATA REGISTRY STUDY OF EXERCISE IN PD

NEURO -PROTECTION AND NEURO -RESTORATIONContinuous, deficit-targeted, intensive training may confer

neuroprotection and thereby slow, stop or reverse the progression of the disease or promote neurorestoration through adaptation of compromised signaling pathways.

However, intensity, duration and task-specific paradigms are likely important.

Barriers PD patients encounter with exercise need to be addressed

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