Parkinson's Disease

Parkinson’s Disease is a movement disorder, which affects each person differently.

What's Parkinson's?

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by muscle stiffness, tremor, and general inability to control voluntary movement. Primarily a movement disorder, Parkinson’s may also affect swallowing and digestion and diminish the control of heart rate, blood pressure, and urinary continence.

What Causes Parkinson's?

The actual cause of Parkinson’s is still unknown. However, research shows that Parkinson’s is related to the brain protein, Synuclein, as it misfolds into toxic shapes and causes damage in Lewy Bodies inside the brain.

What Drives Parkinson's Progression?

Parkinson’s Disease results from a toxic, misfolded Synuclein build-up in the brain from a molecular perspective. The accumulation of misfolded protein Synuclein forms large aggregates referred to as Lewy Bodies inside the brain.

The hallmark motor disorders in Parkinson’s are due to the misfolded Synuclein causing damage to the brain’s substantia nigra region.

Misfolded Synuclein in the spinal fluid (CSF) and Lewy Bodies in the brain are the hallmark biomarkers of a Parkinson’s diagnosis.

Other movement disorders may mimic Parkinson’s early symptoms, leading to frequent misdiagnosis. However, misfolded Synuclein rarely appears in these other forms of Parkinson’s-like disorders.

In most Parkinson’s patients, the brain damage is confined to the substantia nigra, a small area in the midbrain composed of dopamine-producing neurons.

Parkinson's Biomarker

Parkinson’s Disease is almost always associated with a single misfolded protein biomarker: Synuclein.

Produced by most brain cells, Synuclein is abundant throughout the brain. As such, when a normal Synuclein protein goes rogue and starts to misfold, the process can lead to widespread injury to the entire brain. However, the initial misfolding and damage takes place in the substantia nigra region of the midbrain.

When the misfolding and self-replication happens, these misfolded proteins are known as prion-proteins and take on undercover abilities to damage the brain without the body showing any sign or symptoms for years.

The long asymptomatic stage of misfolded Synuclein makes this a target biomarker focus on research efforts to cure Parkinson’s Disease. Learn more about the characteristics of misfolded proteins here.

PD Key Symptoms

The primary symptoms of Parkinson’s include:

  • Muscle stiffness and rigidity,
  • Tremor, and
  • A shuffling walk.

These symptoms result from the permanent loss of dopamine-producing cells in the substantia nigra region of the brain.

In later stages of Parkinson’s, the permanent damage extends beyond the substantia nigra to include memory areas in the hippocampus and cerebral cortex. As these additional brain regions degenerate, symptoms of dementia may follow.

Parkinson’s Four Stages

There are four critical stages of Parkinson’s, representing the progression of symptoms that affect our daily lives.

  1. The prodromal stage

The prodromal stage represents the earliest stage of Parkinson’s Disease before patients experience the classic movement symptoms of rigidity, tremor, and shuffling gait. The prodromal stage symptoms include:

  • Loss of taste and smell,
  • Unusual sleep behaviors and
  • Constipation

However, these are associated with other disorders as well.

  1. Early-stage

Early-stage diagnosis reflects the earliest measurable changes in motor control. These symptoms are unlikely to be noticed by anyone other than the patient.

Early-stage Parkinson’s symptoms have significant overlap with symptoms caused by normal brain aging and other non-progressive motor disorders. Biometric detection using machine learning and molecular biomarkers represents the best chance for diagnosis at this stage.

In particular, biometric tracking of eye movements, vocalization, and typing shows promise as indicators of early-stage Parkinson’s.

  1. Clinical (intermediate) stage

At this stage, the Parkinson’s patient shows one or more noticeable motor disorders, including tremor, rigidity, and shuffling. Drugs such as dopamine precursors and agonists may provide temporary improvement. However, these drugs have significant side effects that include nausea, confusion, and involuntary movements.

  1. Advanced stage

In addition to rapidly declining motor symptoms, patients may show progressive symptoms of dementia and loss of memory resembling Alzheimer’s Disease.

If dementia and memory loss appear at earlier stages of Parkinson’s, doctors might diagnose the condition as Lewy Body Dementia.

Parkinson’s Risk Factors

So far, research has shown the following risk factors that contribute to the development of Parkinson’s condition.

  1. Genetics

Approximately 10-15% of Parkinson’s patients carry genes that may be responsible for the disease. These individuals may have one or more first-degree relatives with Parkinson’s.

For Parkinson’s patients, carrying specific mutations in the GBA-1 or LRRK2 genes significantly increases the lifetime risk of Parkinson’s.

The mechanism of action for any of these genes is not entirely understood.

However, both of these genes may be involved in the accumulation of misfolded proteins.

  1. Mutations in GBA-1 cause the accumulation of specific lipids (fats) in the brain that trigger Synuclein misfolding.
  2. Mutations in LRRK2 may impair the removal and degradation of misfolded Synuclein proteins in nerve cells.

Both mutations increase the level of Misfolded Synuclein, and therefore the risk of Parkinson’s.

  1. Traumatic Head Injuries

There is an increased association of Parkinson’s among athletes with a documented history of multiple head injuries, including multiple concussions. Similarly, Alzheimer’s and other dementias have also shown links to head injuries.

Parkinson’s appears more frequently with repeated traumatic injuries and concussions. Athletes in sports such as boxing, basketball, baseball, and football exhibit higher rates for Parkinson’s. A notable example is Muhammad Ali.

  1. Environmental Effects

Both internal (physical body) and external environments play a role in Parkinson’s Disease.

Internal Environment

The origin of Parkinson’s may result in some people from toxic bacteria in the gastrointestinal (GI) tract. Certain bacteria strains may promote Synuclein misfolding in the gut, and misfolded Synuclein can travel via the vagus nerve(also called cranial nerve X)  from the intestines to the brain. Patients who have had their vagus nerve surgically removed show a decreased relative risk or delayed onset of Parkinson’s in their older years.

External Environment

Toxins from the environment may also contribute to the development of Parkinson’s. However, no particular toxins have been linked directly to early or late-onset disease. Long-term exposure to herbicides, insecticides, and metals in the workplace may increase the risk of Parkinson’s.

PD Isn't An Old Person's Disease

According to a 2003 paper from Kaiser Permanente, Parkinson’s occurrence is more than 100-fold more significant in the seventh decade of life than the fourth.

However, for Parkinson’s patients, research work shows the misfolding of proteins may have already started in the brain during their youth and early adult years. During this Asymptomatic Phase, the destruction of neurons (brain cells) progresses silently and undetected. Clinical symptoms start to show decades later.

Research suggests that Parkinson’s Disease first develops as early as our teens and more frequently in our 20s and 30s. Consider the following:

PD Early Trigger - Misfolded Synuclein

Misfolded Protein Synuclein aggregates have been found in the removed appendices of patients younger than 20, suggesting that Parkinson’s may be triggered relatively early in life (2018 Killinger et al., Science Translational Medicine 10:465).

Misfolded Protein Synuclein Athlete
Muhammad Ali Parkinsons

Multiple Traumatic Head Injuries

Boxers experiencing multiple traumatic head injuries in their prime adult life (the 20s and 30s) have an increased incidence of both cognitive and motor neurodegeneration later in life. The boxing champion, Muhammad Ali, is a prominent example who suffered from Parkinson’s.

Environmental Risk Factors

Michael J Fox, the actor and founder of the Michael J Fox Foundation, was first diagnosed with Parkinson’s at age 29. He attributes the unusually young age of his diagnosis to several possible environmental factors, including Lyme Disease and alcohol abuse, according to a New York Times article published on May 14, 2002.

Michael J Fox Parkinsons MJFF

When people experience symptoms such as loss of motor abilities, this is the clinical-stage. Prion-protein diseases require an accurate diagnosis in the early stages to enable preventive care. 

Early Onset

Research shows that the incidence of Parkinson’s reaches a peak in the sixth decade of life.

Approximately 5% of Parkinson’s patients are diagnosed with early-onset Parkinson’s disease. Michael J. Fox, for example, was diagnosed at age 29.

Research shows that the following group of people may be a high-risk category for PD, including:

  • Athletes and other individuals with histories of multiple head injuries and concussions
  • Individuals with workplace exposures to environmental toxins and metals
  • Individuals with known family histories or genetic predisposition.

Diagnosis

At present, doctors can only diagnose Parkinson’s after clinical symptoms appear when irreversible damage to the brain has already occurred.  As this represents a relatively late-stage  event, it’s no accident that Parkinson’s looks like as a disease of the elderly from a clinical perspective:

However, as discussed earlier, misfolded proteins—the culprit in driving Parkinson’s—pass-through decades of incubation and spreading. During this asymptomatic phase, there is no detection method available presently. But this will change soon, as Amprion and others offer biomarker testing soon. 

Parkinson’s passes a long asymptomatic stage. Destruction of neurons or brain cells starts earlier in life and progresses silently for years, even multiple decades. During the early stages, Parkinson’s causes invisible damage to the brain.

early parkinson's onset

Parkinson’s passes a long asymptomatic stage. Destruction of neurons or brain cells starts earlier in life and progresses silently for years, even multiple decades. During the early stages, Parkinson’s causes invisible damage to the brain.

Frequent Parkinson's Misdiagnosis

One in 4 Parkinson’s cases is misdiagnosed initially. Why is diagnosing Parkinson’s such a daunting challenge? 

Consider this simple fact: the early signs of Parkinson’s (tremor, stiffness, balance disorders, constipation) overlap substantially with signs of normal aging and other neurological diseases.

The overwhelming misdiagnosis of Parkinson’s is why biomarker-testing is the next critical milestone to empowers doctors with accurate Parkinson’s diagnosis.

Parkinson’s Treatment

Patients with early and intermediate-stage Parkinson’s Disease respond initially to drugs that increase dopamine’s brain concentrations. These include:

  • Levodopa, and
  • Carbidopa

However, long-term treatment with these drugs leads to undesired severe side effects, and the benefits may decrease over time.

More recently, implantation of electrodes deep within the brain and stimulation with electrical pulses may improve voluntary movement in a subset of patients.

There is currently no treatment that slows or stops the progression of Parkinson’s. However, scientists and researchers such as Team Amprion are working hard to accelerate drug development to prevent Parkinson’s.

Who Gets Parkinson’s?

Parkinson’s Disease affects men more frequently and severely than women. About 65% of Parkinson’s patients are men. Ironically, the gender bias is reversed in Alzheimer’s as it affects women more frequently and more severely.

parkinson's affects men more than women

Who Gets Parkinson’s?

Parkinson’s Disease affects men more frequently and severely than women. About 65% of Parkinson’s patients are men. Ironically, the gender bias is reversed in Alzheimer’s as it affects women more frequently and more severely.

How Early Detection Helps Delay Onset of Parkinson's?

How Early Detection Helps Delay Onset of Parkinson’s? A recent New York Times article shows that people who consume a diet rich in vitamins C and E may be at reduced risk for Parkinson’s disease. Read the study published in Neurology

How Early Detection Helps Delay Onset of Parkinson's?

9 dragons tea-healthy foods vitamine-c-vitimine-e

Parkinson's Disease Frequently Asked Questions

Parkinson's primarily affects a region of the midbrain called the substantia nigra. Brain cells in this region produce high concentrations of the neurotransmitter dopamine and help initiate and control voluntary movements. Early stage Parkinson's patients can also show evidence of the disease in the brainstem. Late stage Parkinson's patients may show evidence of the disease in the hippocampus, which controls memories and the cerebral cortex which controls higher level thinking and planning.
Approximately 10% of patients with Parkinson's disease are believed to have inherited or genetic forms of the disease. The vast majority of patients do not appear to have any genetic or familal predisposition. Genes that can increase the probability of Parkinson's include SNCA, LRRK2, PARKIN, PINK1 and GBA.
Parkinson's Disease is caused by the loss of neurons in the substantia nigra region of the midbrain. At present, there are no treatments that can restore these cells or their connections. However, several treatments can substitute for the lost cells, at least temporarily. Cells of the substantia nigra produce and release large amounts of the neurotransmitter, dopamine. L-DOPA is a precursor drug that is converted in the brain to dopamine and can restore some lost functions in Parkinson's patients. In addition, the electrical activity of cells in the substantia nigra can be mimicked by sending electrical pulses through thin wires embedded selectively in brain regions where signals from the substantia nigra have been lost.
Patients with Parkinson's Disease can progress over time to dementia that further complicates the usual motor symptoms. In addition, some Parkinson's patients show signs of early dementia at the same time that the typical motor symptoms present. In some patients, the dementia associated with Parkinson's is difficult to distinguish from Alzheimer's Disease. For these reasons, it may be helpful to view Alzheimer's and Parkinson's as two diseases along a spectrum of related diseases, which has been referred to as the Parkinzheimer Spectrum.
Parkinson's Disease appears to have different causes in different people. In approximately 10% of cases, the cause appears to be genetic or familial. Other patients with Parkinson's share a history of repeated head traumas, as seen in boxers and some soldiers. Still other patients appear to show a link to abnormalities in the gut and possibly the bacteria that colonize the gut. Once Parkinson's has been started, it slowly progresses and moves through different regions of the brain including the substantia nigra of the midbrain, which is responsible for the classical motor symptoms of the disease.
The earliest clinical signs associated with Parkinson's disease tend to be distinct from the motor symptoms most commonly associated with Parkison's. These "prodromal signs" include constipation not linked to other known problems, sleep disorders mainily associated with the rapid-eye-movement (REM) phase of sleep, and loss of sense of smell and taste. For individuals with one of these symptoms, approximately 60% go on within 10 years to develop clinical symptoms associated with Parkinson's. It is possible that treatment of patients at this prodromal stage may slow or prevent the eventual onset of Parkinson's symptoms
Medical science has proven time and again that when the resources are provided, great progress in the treatment, cure, and prevention of disease can occur.
Michael J Fox Parkinsons MJFF
Michael J. Fox
Actor & Founder of The Michael J. Fox Foundation