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Parkinson's disease (paralysis agitans or PD) is a movement disorder often characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia), and in extreme cases, a loss of physical movement (akinesia). The primary symptoms are due to excessive muscle contraction, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Parkinson's disease was first formally recognised and its symptoms documented in 1817 in An Essay on the Shaking Palsy by the British physician Dr James Parkinson. The associated biochemical changes in the brains of patients were identified in the 1960s.

Symptoms

Parkinson disease affects movement (motor symptoms). Typical other symptoms include disorders of mood, behavior, thinking, and sensation (non-motor symptoms). Individual patients' symptoms may be quite dissimilar; progression is also distinctly individual.

There are four major dopamine pathways in the brain; the nigrostriatal pathway, referred to above, mediates movement and is the most conspicuously affected in early Parkinson's disease. The other pathways are the mesocortical, the mesolimbic, and the tuberoinfundibular. These pathways are associated with, respectively: volition and emotional responsiveness; desire, initiative, and reward; and sensory processes and maternal behavior. Reduction in dopamine along the non-striatal pathways is the likely explanation for much of the neuropsychiatric pathology associated with Parkinson's disease.

Motor symptoms

The cardinal symptoms of Parkinson's disease form a classic tetrad. These may be absent or subtle in early cases:

• tremor: 4-7Hz tremor, maximal when the limb is at rest, and decreased with voluntary movement. It is typically unilateral at onset. This is the most apparent and well-known symptom. However, an estimated 30% of patients have little perceptible tremor; these are classified as akinetic-rigid.
• rigidity: stiffness; increased muscle tone. In combination with a resting tremor, this produces a ratchety, "cogwheel" rigidity when the limb is passively moved.
• bradykinesia/akinesia: respectively, slowness or absence of movement. Rapid, repetitive movements produce a dysrhythmic and decremental loss of amplitude.
• postural instability: failure of postural reflexes, which leads to impaired balance and falls.

Other motor symptoms include:

• Gait and posture disturbances:
  • Shuffling: gait is characterized by short steps, with feet barely leaving the ground, producing an audible shuffling noise. Small obstacles tend to trip the patient
  • Decreased arm swing: a form of bradykinesia
  • Turning "en bloc": rather than the usual twisting of the neck and trunk and pivoting on the toes, PD patients keep their neck and trunk rigid, requiring multiple small steps to accomplish a turn.
  • Stooped, forward-flexed posture. In severe forms, the head and upper shoulders may be bent at a right angle relative to the trunk (camptocormia).
  • Festination: a combination of stooped posture, imbalance, and short steps. It leads to a gait that gets progressively faster and faster, often ending in a fall.
  • Gait freezing: "freezing" is another word for akinesia, the inability to move. Gait freezing is characterized by inability to move the feet, especially in tight, cluttered spaces or when initiating gait.
  • Dystonia: abnormal, sustained, painful twisting muscle contractions, usually affecting the foot and ankle in PD patients. This causes toe flexion and foot inversion, interfering with gait.
• Speech and swallowing disturbances
  • Hypophonia: soft speech. Speech quality tends to be soft, hoarse, and monotonous.
  • Festinating speech: excessively rapid, soft, poorly-intelligible speech.
  • Drooling: most likely caused by a weak, infrequent swallow and stooped posture.
  • (Non-motor causes of speech/language disturbance in both expressive and receptive language: these include decreased verbal fluency and cognitive disturbance especially related to comprehension of emotional content of speech and of facial expression
  • Dysphagia: impaired ability to swallow. Can lead to aspiration, pneumonia, and ultimately death.
• Other motor symptoms:
  • fatigue (up to 50% of cases);
  • masked facies (a mask-like face also known as hypomimia), with infrequent blinking;
  • difficulty rolling in bed or rising from a seated position;
  • micrographia (small, cramped handwriting);
  • impaired fine motor dexterity and coordination;
  • impaired gross motor coordination,
  • Poverty of movement: overall loss of accessory movements, such as decreased arm swing when walking, as well as spontaneous movement.

Non-motor symptoms

Mood disturbances:

Estimated prevalance rates of depression vary widely according to the population sampled and methodology used. Reviews of depression estimate its occurrence in anywhere from 20-80% of cases. Estimates from community samples tend to find lower rates than from specialist centres. Most studies use self-report questionnaires such as the Beck Depression Inventory which may overinflate scores due to physical symptoms. Studies using diagnostic interviews by trained psychiatrists also report lower rates of depression.

More generally, there is an increased risk for any individual with depression to go on to develop Parkinson's disease at a later date .

70% of individuals with Parkinson's disease diagnosed with pre-existing depression go on to develop anxiety. 90% of Parkinson's disease patients with pre-existing anxiety subsequently develop depression); apathy or abulia.

Cognitive disturbances:

• slowed reaction time; both voluntary and involuntary motor responses are significantly slowed.
• executive dysfunction, characterized by difficulties in: differential allocation of attention, impulse control, set shifting, prioritizing, evaluating the salience of ambient data, interpeting social cues, and subjective time awareness. This complex is present to some degree in most Parkinson's patients; it may progress to:
• dementia: a later development in approximately 20-40% of all patients, typically starting with slowing of thought and progressing to difficulties with abstract thought, memory, and behavioral regulation.
• memory loss; procedural memory is more impaired than declarative memory. Prompting elicits improved recall.
• medication effects: some of the above cognitive disturbances are improved by dopaminergic medications, while others are actually worsened

Sleep disturbances:

• Excessive daytime somnolence;
• Initial, intermediate, and terminal insomnia;
• Disturbances in REM sleep: disturbingly vivid dreams, and REM Sleep Disorder, characterized by acting out of dream content;

Sensation disturbances:

• impaired visual contrast sensitivity, spatial reasoning, colour discrimination, convergence insufficiency (characterized by double vision) and oculomotor control
• dizziness and fainting; usually attributable orthostatic hypotension, a failure of the autonomous nervous system to adjust blood pressure in response to changes in body position
• impaired proprioception (the awareness of bodily position in three-dimensional space)
• loss of sense of smell (anosmia),
• pain: neuropathic, muscle, joints, and tendons, attributable to tension, dystonia, rigidity, joint stiffness, and injuries associated with attempts at accommodation

Autonomic disturbances:

• oily skin and seborrheic dermatitis;
• urinary incontinence, typically in later disease progression
• constipation and gastricdysmotility: severe enough to endanger comfort and even health
• altered sexual function: characterized by profound impairment of sexual arousal, behavior, orgasm, and drive is found in mid and late parkinson disease. Current data addresses male sexual function almost exclusively.

Epidemiology

The worldwide prevalence of Parkinson's disease is 4 to 6 million people. There are over 1.5 million in China alone. It is likely that there are millions of people with Parkinson's disease that remain undiagnosed. Prevalence estimates range from a low of 7 per 100,000 in Ethiopia to a high of 329.3 per 100,000 in Nebraska, U.S.A., and 328.3 cases per 100,000 in the Parsi community in Bombay, India. The greatest prevalence of any country is the U.S.A., with between 100 and 250 cases per 100,000.

The average age at which symptoms begin is 55-60, and although cases at ages as low as 11 have been reported it is highly unusual for people under 30 to develop Parkinson's. The risk of developing it substantially increases with age. It occurs in all parts of the world, but appears to be more common in people of European ancestry than in those of African ancestry. Those of East Asian ancestry have an intermediate risk. It is more common in rural than urban areas and men are affected slightly more than women. About 2% of the population develops the disease some time during life.

Related diseases

Parkinsonian symptoms may occur in the context of other conditions. A specific group is that of the Parkinson-Plus diseases. These include:

• Multiple system atrophy (MSA) (incorporating the outdated conditions Shy-Drager syndrome (SDS), striatonigral degeneration (SND) and olivopontocerebellar atrophy (OPCA))
• Progressive supranuclear palsy (PSP)
• Corticobasal degeneration (CBD)

Other related conditions are:

• Cerebellar thoracic outlet syndrome
• Vascular parkinsonism
• Encephalitis lethargica
• Essential tremor
• Wilson's disease
• Hydrocephalus

Pathology

The interaction of dopamine and acetylcholine

The primary symptoms of Parkinson's Disease are due to excessive muscle contraction.

Acetylcholine affects muscle contraction via the five cholinergic receptors : m1, m2, m3, m4, and m5. The receptors m1, m3 and m5 are stimulatory. The receptors m2 and m4 are inhibitory. The combined stimulatory effect of m1, m3 and m5 is more powerful in total than the combined inhibitory effect of m2 and m4. So the overall effect of acetylcholine is to stimulate muscle contraction.

Dopamine affects muscle contraction via the five dopamine receptors : D1, D2, D3, D4, and D5. The receptors D2, D3 and D4 are inhibitory. The receptors D1 and D5 are stimulatory. The combined inhibitory effect of D2, D3 and D4 is more powerful in total than the combined stimulatory effect of D1 and D5. So the overall effect of dopamine is to inhibit muscle contraction.

Parkinson's Disease consequently occurs when the effect of dopamine is less than that of acetylcholine. Dopamine deficiency rather than acetylcholine excess is normally responsible for this occurring.

Symptoms usually only begin to appear after a reduction down to about 25% of the normal activity of the dopaminergic neurons. The level of dopamine tends to continue to fall slowly over time, with an attendant worsening of symptoms. The biochemistry of Parkinson's Disease

Dopamine biosynthesis

The primary fault in Parkinson's Disease is that, whatever the cause, there is insufficient dopamine. Dopamine is formed in the dopaminergic neurons by the following pathway :

L-tyrosine >>> L-dopa >>> Dopamine

The first step is biosynthesised by the enzyme Tyrosine 3-Monooxygenase (which is more commonly called by its former name tyrosine hydroxylase). The following is the complete reaction :

L-tyrosine + THFA + O2 + Fe2+ >>> L-dopa + DHFA + H2O + Fe2+

So for L-dopa formation, L-tyrosine, THFA (tetrahydrofolic acid), and ferrous iron are essential. The activity of this enzyme is often as low as 25% in Parkinson's Disease, and in severe cases can be as low as 10%. This indicates that one or more of the elements required for the formation of L-dopa are in insufficient quantities.

The second step in the biosynthesis of dopamine is biosynthesised by the enzyme Aromatic L-amino acid decarboxylase (which is more commonly called by its former name dopa decarboxylase). The following is the complete reaction :

L-dopa + pyridoxal phosphate >>> dopamine + pyridoxal phosphate + CO2

So for dopamine biosynthesis from L-dopa, pyridoxal phosphate is essential. The activity of the enzyme rises and falls according to how much pyridoxal phosphate there is. The level of this enzyme in Parkinson's Disease can also be around 25% or even far less. The biochemistry of Parkinson's Disease

Coenzymes involved in dopamine biosynthesis

Besides two enzymes being required for the formation of dopamine from L-tyrosine (L-tyrosine >>> L-dopa >>> Dopamine), three coenzymes are also required. Enzymes are substances that will enable a specific chemical reaction to take place in the body. Coenzymes are substances that assist enzymes. Some enzymes (including those involved in dopamine biosynthesis) will not function without coenzymes.

The three coenzymes involved in the formation of dopamine are : THFA (for L-tyrosine to L-dopa), Pyridoxal phosphate (for L-dopa to dopamine), and NADH (for the formation of THFA and Pyridoxal phosphate). They are made from vitamins via the following means :

Folic acid >>> Dihydrofolic acid >>> Tetrahydrofolic acid

Pyridoxine >>> Pyridoxal >>> Pyridoxal 5-Phosphate (this requires zinc as a cofactor)

Nicotinamide >>> NMN >>> NAD >>> NADH (or NADP) >>> NADPH

The biochemistry of Parkinson's Disease: Coenzymes

G-proteins

In order to relieve Parkinson's Disease, dopamine (or dopamine agonists) must stimulate dopamine receptors, which must in turn stimulate the G proteins :

L-tyrosine > L-dopa > dopamine > dopamine receptors (D2, D3, D4) > G proteins

G proteins consist of three parts : alpha - beta - gamma, that are lined to each other. There are three types of beta unit (1, 2, 4), and seven types of gamma unit (2, 3, 4, 5, 7, 10, 11). However, they do not matter much to Parkinson's Disease. What matters to Parkinson's Disease are the alpha subunits, because it is actually these that ultimately relieve (or aggravate) Parkinson's Disease. There are five types :

• G proteins that aggravate Parkinson's Disease : Gs 1 alpha
• G proteins that relieve Parkinson's Disease : Gi 1 alpha, Gi 2 alpha, Gi 3 alpha
• G proteins that have little effect on Parkinson's Disease : Go alpha

The sole purpose of dopamine (or dopamine agonists) stimulating dopamine receptors is to cause the alpha subunits (the active part of G proteins) to break away from the rest of the G protein. Without this occurring almost everybody would have Parkinson's Disease. Once the alpha part of G proteins is released, via cyclic AMP, it takes the final action in the series of event that leads to the ridding of Parkinson's Disease, which is to inhibit the cells it has effect on.The biochemistry of Parkinson's Disease: G proteins

Neuromelanin

In the cells involved in Parkinson's Disease (the dopaminergic neurons) the function is to produce dopamine. In the melanocytes, which are in the skin, the function is to produce the pigment melanin. Melanin is what causes people to suntan. Although they end up with different substances (dopamine and melanin), both of these cells start off with L-tyrosine, and both of them form L-dopa as well :

dopaminergic neurons : L-tyrosine > L-dopa > dopamine

melanocytes : L-tyrosine > L-dopa > melanin

In the dopaminergic neurons, when somebody can not form dopamine, they can accidentally form melanin instead. In the brain it is called neuromelanin because of the different amino acids it is attached to. However, this is not a normal mechanism, and it occurs via a different mechanism from that found in the skin. The formation of neuromelanin in the brain is often claimed to be what happens in healthy brains. Healthy brains are supposed to be darker in the part of the brain called the substantia nigra. However, it is actually due to the biochemical mechanisms not working properly. As not much L-dopa is formed in Parkinson's Disease, there isn't much capacity for that L-dopa to accidentally form melanin in the brain. So people with Parkinson's Disease can tend to have not much pigment in the part of the brain called the substantia nigra. However, that does not cause a medical problem because melanin is not supposed to be in the brain.The biochemistry of Parkinson's Disease: Neuromelanin

Cell damage

The primary natural means via which cell damage can occur in Parkinson's Disease is due to the reaction from L-tyrosine to L-dopa not taking place. The following is what should happen :

L-tyrosine + THFA + O2 + Fe2+ >>> L-dopa + DHFA + H2O + Fe2+

However, if for example, the THFA in the above reaction is lacking, the following can happen instead :

L-tyrosine + Fe2+ + O2 >>> L-tyrosine + Fe3+ + O-2 (superoxide anion)

As can be seen there is no L-dopa formed in the faulty reaction, and the superoxide anion is formed instead. The superoxide anion is one of the most highly destructive elements in cells. The formation of L-dopa can also fail to take place if L-tyrosine is deficient.

So the simplest means of preventing cell damage from taking place is to ensure that you have those substances required for the formation of L-dopa, which are L-tyrosine, THFA (which is made from the vitamin folic acid using nicotinamide), and ferrous iron.

Vitamin C and Vitamin E have been used to try to help to prevent cell damage in Parkinson's Disease. This is because they are claimed to assist in two enzyme reactions in the brain that get rid of the superoxide anion once it has been formed :

Superoxide Dismutase  : 2O-2 + 2H+ >>> H2O2 + O2

Catalase  : H2O2 >>> H2O + 1/2 O2

However, the problem with the use of Vitamin C and Vitamin E in trying to prevent cell damage is that they do nothing at all to prevent the original source of the problem, which is the formation of superoxide anion.The biochemistry of Parkinson's Disease: Cell damage

Lewy bodies

Lewy bodies are found in the cytoplasm of neurons, and are composed of densely aggregated filaments. These filaments contain ubiquitin and alpha-synuclein. Lewy Bodies are often associated with Parkinson's Disease. However, they are not unique to Parkinson's Disease, as they also occur in several other medical disorders.

Pathophysiology

Most people with Parkinson's Disease are described as having idiopathic Parkinson's Disease (having no specific cause). There are far less common causes of Parkinson's Disease including genetic, toxins, head trauma, and drug induced Parkinson's Disease.

Head trauma

Past episodes of head trauma are reported more frequently by sufferers than by others in the population. A methodologically strong recent study found that those who have experienced a head injury are four times more likely to develop Parkinson’s disease than those who have never suffered a head injury. The risk of developing Parkinson’s increases eightfold for patients who have had head trauma requiring hospitalization, and it increases 11-fold for patients who have experienced severe head injury.

Drug-induced

Antipsychotics, which are used to treat Schizophrenia and Psychosis, can induce the symptoms of Parkinson's Disease by lowering dopaminergic activity. Due to feedback inhibition, L-dopa can eventually cause the symptoms of Parkinson's Disease that it initially relieves. Dopamine receptors can also eventually contribute to Parkinson's Disease symptoms due to making the dopamine receptors increasingly less sensitive.

Treatments

Levodopa

The most widely used form of treatment is L-dopa in various forms. L-dopa is transfomed into dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase (often known by its former name dopa-decarboxylase). However, only 1-5% of L-DOPA enters the dopaminergic neurons. The remaining L-DOPA is often metabolised to dopamine elsewhere, causing a wide variety of side effects. Due to feedback inhibition, L-dopa results in a reduction in the endogenous formation of L-dopa, and so eventually becomes counterproductive.

Carbidopa and Benserazide are dopa decarboxylase inhibitors. They help to prevent the metabolism of L-dopa before it reaches the dopaminergic neurons.

Talcopone inhibits the COMT enzyme, thereby prolonging the effects of L-Dopa, and so has has been used to complement L-dopa. However, due to its side effects, such as possible liver failure is limited in its availability. A similar drug, entacapone, has similar efficacy and has not been shown to cause significant alterations of liver function.

Sinemet contains L-dopa and also carbidopa. Parcopa contains the same two drugs but is orally disintegrating. Madopar contains L-dopa and benserazide. There are also controlled release versions of Sinemet and Madopar that spread out the effect of the L-dopa. Duodopa is a combination of levodopa and carbidopa, dispersed as a viscous gel. Using a patient-operated portable pump, the drug is continuously delivered via a tube directly into the upper small intestine, where it is rapidly absorbed. Stalevo contains Levodopa, Carbidopa and Entacopone. Mucuna pruriens, is a natural source of therapeutic quantities of L-dopa.

Dopamine agonists

The Dopamine-agonists bromocriptine (Parlodel), pergolide (Permax), pramipexole (Mirapex), ropinirole (Requip), cabergoline (Cabaser), apomorphine (Apokyn), and lisuride (Revanil), are moderately effective. These have their own side effects including those listed above in addition to somnolence, hallucinations and /or insomnia. Dopamine agonists initially act by stimulating some of the dopamine receptors. However, they cause the dopamine receptors to become progressively less sensitive, thereby eventually increasing the symptoms.

MAO-B inhibitors

Selegiline (Eldepryl) and Rasagiline (Azilect) reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B), which inhibits the breakdown of dopamine secreted by the dopaminergic neurons. By-products of selegiline include amphetamine and methamphetamine - each can have side effects that damage tha Dopaminergic neurons. Use of L-DOPA in conjunction with Selegiline has increased mortality rates that have not been effectively explained.

Surgical interventions

Deep brain stimulation is presently the most used surgical means of treatment.

Gene therapy involves using a harmless virus to shuttle a gene into a part of the brain called the subthalamic nucleus (STN). The gene used leads to the production of an enzyme called glutamic acid decarboxylase (GAD), which catalyses the production of a neurotransmitter called GABA. GABA acts as a direct inhibitor on the overactive cells in the STN.

GDNF infusion involves, by surgical means, the infusion of GDNF (glial-derived neurotrophic factor)into the basal ganglia using implanted catheters. Via a series of biochemical reactions, GDNF stimulates the formation of L-dopa. GDNF therapy is still in development.

In the future, implantation of cells genetically engineered to produce dopamine or stem cells that transform into dopamine-producing cells may become available. Even these, however, will not constitute cures because they do not address the considerable loss of activity of the dopaminergic neurons.

Nutrients

Nutrients have been used in clinical studies and are widely used by people with Parkinson's Disease in order to partially treat Parkinson's Disease or slow down its deterioration. The L-dopa precursor L-tyrosine was shown to relieve an average of 70% of symptoms. Ferrous iron, the essential cofactor for L-dopa biosynthesis was shown to relieve between 10% and 60% of symptoms in 110 out of 110 patients. Also used alongside existing treatments is a Parkinson's Disease supplement that contains both of these substances and all the other nutrients required for dopamine formation. More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxine - coenzymes and coenzyme precursors involved in dopamine biosynthesis. Vitamin C and Vitamin E in large doses are commonly used by patients in order to lessen the cell damage that occurs in Parkinson's Disease. This is because the enzymes Superoxide Dismutase and Catalase require these vitamins in order to nullify the superoxide anion, a toxin commonly produced in damaged cells. Coenzyme Q10 has more recently been used for similar reasons. MitoQ is a newly developed synthetic substance that is similar in structure and function to Coenzyme Q10.

Physical exercise

Regular physical exercise and/or therapy, including in forms such as yoga, tai chi, and dance can be beneficial to the patient for maintaining and improving mobility, flexibility, balance and a range of motion.

Prognosis

Most older studies have noted increased mortality in patients with Parkinson disease (PD). However, the 2005 Rotterdam Study, which prospectively followed a large cohort of participants, noted only a modest decrease in survival in patients without dementia. A 2004 community-based cohort study of 245 PD patients demonstrated similar findings in patients with clinically definite PD.

The most commonly reported cause of death in PD patients is pneumonia. Swallowing difficulties may lead to aspiration of food, causing aspiration pneumonia (a specific form of pneumonia caused by gastric acid, food and digestive tract bacteria). Onset of dementia doubles the odds of death. Depression more than doubles the odds ratio.

References

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2. Günther Deuschl, Christof Goddemeier (1998). "Spontaneous and reflex activity of facial muscles in dystonia, Parkinson's disease, and in normal subjects". Journal of neurology, neurosurgery, and psychiatry. 64 (March): 320–324.
3. Michael J Frank (2005). "Dynamic Dopamine Modulation in the Basal Ganglia: A Neurocomputational Account of Cognitive Deficits in Medicated and Non-mediacated Parkinsonism". Journal of Cognitive Neuroscience. 17: 51–73.
4. J. H. Bower; et al. (2003). "Head trauma preceding PD". Neurology. 60: 1610–1615. {{cite journal}}: Explicit use of et al. in: |author= (help)
5. M. Stern; et al. (1991). "The epidemiology of Parkinson's disease". Archives of Neurology. 48 (9): 903–907. {{cite journal}}: Explicit use of et al. in: |author= (help)
6. ^ K Uryu; et al. (2003). "Age-dependent synuclein pathology following traumatic brain injury in mice". Experimental neurology. 184 (1): 214–224. {{cite journal}}: Explicit use of et al. in: |author= (help)
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8. W. Birkmayer and J. G. D. Birkmayer (1986). "Iron, a new aid in the treatment of Parkinson patients". Journal of Neural Transmission. 67 (3–4): 287–292.
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10. Lonneke M. L. de Lau; et al. (2005). "Prognosis of Parkinson Disease". Archives of Neurology. 62 (8): 1265–1269. {{cite journal}}: Explicit use of et al. in: |author= (help)
11. Karen Herlofson; et al. (2004). "Mortality and Parkinson disease". Neurology. 62: 937–942. {{cite journal}}: Explicit use of et al. in: |author= (help)
12. TA Hughes, HF Ross, RHS Mindham, EGS Spokes (2004). "Mortality in Parkinson's disease and its association with dementia and depression". Acta Neurologica Scandinavica. 110 (2): 118.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links

• The Parkinson's Disease Forum - new research, news reports, new books, web sites
• European Parkinson's Disease Association
• Parkinson Society Canada
• Parkinson's Disease Foundation
• Hope For A Cure Foundation for Parkinson's Research
• Dr. Abe Lieberman's Ask the Doctor Parkinson Forum
• National Parkinson Foundation, Inc.
• American Parkinson's Disease Association
• Michael J. Fox Foundation for Parkinson's Research
• Parkinson's Disease Society (UK)
• Parkinson's NSW (In AUS)
• MyParkinsonsInfo.com
• The PD Webring
• WEMOVE: Worldwide education and awareness for movement disorders
• NETRP Web site
• Northwest Parkinson's Foundation
• Parkinson's Resources on the WWWeb
• Parkinson's Disease Pictures
• Parkinson's Drug Comparison Chart (PDF)
• Can We Prevent Parkinson’s and Alzheimer’s Disease? Article from Journal of Postgraduate Medicine
• International Society for Posture and Gait Research (ISPGR)
• HollyRod Foundation
• Parkinson's speech wikibook
• Lee Silverman Voice Therapy

• Human diseases
• Eponymous diseases
• Geriatrics
• Neurological disorders