PARKINSON'S DISEASE
AND THE SCIENCE BEHIND EXERCISE
A Progressive Neurodegenerative Disorder
In 1817, Dr. James Parkinson described what he termed "shaking palsy" in the medical literature, based on his observation of six people exhibiting similar symptoms He detailed tremor, muscle weakness, altered gait, and posture as components of a single disease that would later carry his name. Since these first case reports, many therapies have been investigated However, it wasn't until 1961 that levodopa, a drug first isolated in legumes, provided patients with dramatic symptom relief allowing previously bedridden patients to walk.
Parkinson's disease is caused by the destruction of dopamine-producing neurons in the part of the brain called the substantia nigra Dopamine is a neurotransmitter best known for its role in motor, motivation, and pleasure control Parkinson's disease typically manifests later in life (past the age of 50 years) and is characterized by tremors and a shuffling gait It is the second most common neurodegenerative disease after Alzheimer's disease
Diagnosis of Parkinson's disease occurs at the onset of motor symptoms when half or more of the brain's dopaminergic neurons are lost However, symptoms of the disease are not exclusively related to movement; non-motor symptoms, including constipation, loss of smell, and depression, often precede diagnosis by several years This constellation of non-motor features, while not diagnostic of Parkinson's disease, can alert clinicians to a person at risk.
Medication: Levodopa - a treatment, not a cure
Levodopa, also known as L-dopa, is a dopamine precursor commonly used to replace dopamine in Parkinson's disease. L-dopa performs a dual role by participating in synapse formation and relieving symptoms of slowness and stiffness However, L-dopa's effectiveness diminishes as the disease progresses, and many patients develop levodopa-induced dyskinesias uncontrolled, involuntary movements that range from jerking and twisting movements to muscle spasms of varying severity People who have dyskinesias often describe a diminished quality of life due to the physical pain or embarrassment that their movement disorder can cause.
A tragic event that propelled parkinson's disease research forward
In the early 1980s, seven people developed parkinsonian features overnight. Investigative work revealed that during the illicit manufacturing of synthetic heroin, a batch of the drug was contaminated with MPTP, a neurotoxin precursor that, once activated, inhibits mitochondrial function, and kills dopamine-producing neurons MPTP is chemically related to the pesticides rotenone and paraquat, which can produce parkinsonian features in animals. This incident led to the creation of the first animal models of Parkinson's disease and validated the idea that environmental exposure to toxicants, the burden of which sometimes can be seen clinically through evidence of increased xenobiotic metabolism in the gut microbiome, could contribute to a neurodegenerative disorder
The role of genetic mutations in Parkinson's disease
But genetics clearly play a role in the pathogenesis of Parkinson's disease Genetic mutations are associated with early-onset (younger than 50 years) disease, most notably mutations in the leucine-rich repeat kinase 2, or LRRK2, gene In cases of late-onset disease (older than 50 years), the picture is less clear, and a complex interaction between genetic and environmental risk factors appears to play a role. Epidemiological data suggest that rural living and occupational use of pesticides may be risk factors
LIFESTYLE FACTORS, INCLUDING EXRCISE PROVE CRUCIAL
MANAGEMENT OF PARKINSON'S DISEASE
"Exercise offers us this model to understand all the reparative and resilience mechanisms that we believe at the end of the day are playing out at a circuit level " - Giselle Petzinger, M D
Compelling epidemiological data point to exercise's ability to reduce the risk of developing Parkinson's disease. But exercise also helps manage its symptoms once the disease develops. Exercise activates pathways that are involved in maintaining connections between neurons, making them stronger and repairing damage. Physical activity, along with other lifestyle factors, such as diet and social and intellectual engagement, may act as a counterbalance against the insults that increase Parkinson's disease risk, such as genetic mutations, environmental exposures, and a sedentary lifestyle.
Adopting healthy lifestyle factors may help improve threshold for Parkinson’s disease.
Physical activities that incorporate learning or skill development are particularly beneficial Skilled exercises including tennis, yoga, and tai chi involve goal-oriented movement in which accuracy is important to accomplish the desired outcome Evidence from animal studies suggests that skilled exercise enhances blood flow to cognitive circuits, which is a marker of cerebrovascular function. Other preclinical research indicates that skilled exercise switches on the activity of hypoxia-inducible factor 1alpha, commonly known as HIF-1α a master transcription factor that influences how more than 40 genes are transcribed Some of these genes allow neurons to signal the body for fuel and growth factors, which may help the parkinsonian brain respond to injury
But exercise intensity matters, too. Intensive exercise training heightens dopamine sensitivity and increases growth factors in the brains of people with Parkinson's disease, leading to improved cognitive performance and postural control two aspects with a profound impact on a person's quality of life.
A growing body of evidence suggests that the numerous benefits of exercise also contribute to the wellbeing of people with Parkinson's disease One intervention study demonstrated that patients performing high-intensity exercise showed no disease progression over six months, while non-exercisers experienced a 15 percent worsening of motor symptoms remarkable results in light of the fact that no drug or treatment has been shown to slow disease progression.
Executive function, attention and memory, and global cognitive function improved after either aerobic or resistance exercise in people with Parkinson’s disease Exercise also improved disease severity (analysis of 11 randomized controlled trials)
Some of the mechanisms include exercise-induced production of brain-derived neurotrophic factor (BDNF), IGF-1, dopamine, and other neurotransmitters.
This analysis of 11 studies and other studies suggest that exercise seems to improve specific measures of cognitive function and slow disease severity in people with Parkinson’s disease