Parkinson’s disease is a progressive disorder of the nervous system that mainly affects the motor system. The symptoms usually develop gradually. The primary and most obvious motor symptoms are resting tremor, slowness of movement, muscle stiffness, and postural instability. Thinking and behavioral problems may also occur. Prominent cognitive problems become common in the advanced stages of the disease.

The direct cause of Parkinson's disease is unknown, but both genetic and environmental factors may play a role. Persons with a family member who has Parkinson’s disease and people who are exposed to certain pesticides are more likely to get the disease than others. 

The disease results from the death of the cells in the substantia nigra of the midbrain, causing dopamine deficiency. The reason for why these cells die is not understood enough, but involves the build-up of proteins into Lewy bodies in the neurons. 

Diagnosis of typical cases is mainly based on symptoms, with some tests, such as neuroimaging, to rule out other diseases.

There is no specific treatment for Parkinson's disease. Medications are generally used treat Parkinson’s disease. These medications include levodopa, and dopamine agonists. Alzheimer’s diseases medications become less efficient as the diseases progresses and may cause complications.

There is no known way to prevent Alzheimer’s disease, but certain measures, such physical activity, may help reduce the risk.

According to Parkinson's Disease Foundation, more than 10 million people worldwide live with Parkinson's disease. Parkinson’s disease is more common in men than in women.

Parkinson’s disease is a progressive disorder of the nervous system that mainly affects the motor system. It develops gradually, starting with a hardly obvious tremor in just one hand. A tremor may be the most well-known sign of Parkinson’s disease. The disorder usually causes stiffness or slowing of movement. In the early stages of Parkinson’s disease, the face may show little or no expression, or the arm may not swing during walking. Speech may become soft or slurred. As the condition progresses over time, the symptoms of Parkinson’s disease become worse.

The direct cause of the nerve cell loss associated with Parkinson’s disease is unknown, but several factors, such as genetics and environmental factors appear to play a role.

 Risk factors that increase the probability of getting Parkinson's disease include:

 * Genetics: The exact way of how genetics make some people more susceptible to the disease is unclear. A number of genetic factors have been shown to increase a person's risk of developing Parkinson’s disease. In rare cases with many family members affected by the disease, specific genetic mutations occur that can cause it.  

* Environmental factors: Exposure to certain environmental factors like pesticides and herbicides used in farming, or being exposed to toxins resulting from industrial pollution, for instance, may increase the risk of developing Parkinson’s disease, but the risk is relatively small.

* Age: The risk of having Parkinson’s disease increases with age. Usually, people develop the disease around age 60 or older.

* Gender: Men are more likely to develop Parkinson’s disease than women.

No specific, standard criteria exist for the neuropathological diagnosis of Parkinson’s disease, as the specificity and sensitivity of its characteristics have not been clearly established. However, two major neuropathologic findings have been proposed in Parkinson’s disease.

The first is loss of pigmented dopaminergic neurons in a part of the substantia nigra known as pars compacta. The substantia nigra is a structure in the midbrain that helps control movement and coordination. The loss of dopamine neurons occurs most prominently in the ventral lateral substantia nigra. The majority of dopaminergic neurons are lost before the motor signs of Parkinson’s disease emerge.

In normal humans, signals from the cerebral cortex are processed through the basal ganglia-thalamocortical motor circuit and return to the same area via a feedback pathway. Output from the motor circuit is directed through the internal segment of the globus pallidus and the substantia nigra pars reticulata. 

Two pathways exist within the basal ganglia circuit, the direct and indirect pathways. Dopamine is released from the substantia nigra pars compacta to activate the direct pathway and inhibit the indirect pathway. In Parkinson’s disease, decreased striatal dopamine causes increased inhibitory output of the motor circuit via both the direct and indirect pathways.

The other neuropathologic finding in Parkinson’s diseases is the abnormal build-up of protein deposits, known as Lewy bodies, in neurons.

Parkinson’s disease symptoms vary from person to person, and usually start mild and may go unnoticed as they develop gradually. According to Parkinson's Disease Foundation, the symptoms of the disease are classified into: 

• Primary Motor Symptoms: The three main primary motor symptoms of Parkinson's disease include:

• Resting Tremor: The tremor consists of a shaking or oscillating movement. In early stages of the disease, the majority of patients suffer from mild tremor in the hand or foot on one side of the body, or less commonly in the jaw or face. This symptom is called resting tremor because it usually appears when the patient’s muscles are relaxed. Stress or excitement can worsen the tremor of Parkinson's disease. When the disease progresses the tremor spreads to the other side of the body.
• Bradykinesia (slowness of movement): As the disease progresses, the patient’s ability to move decreases or movement becomes slower. Decreased in spontaneous movement and facial expressivity become observable. Daily simple tasks, such as buttoning a shirt, cutting food or brushing teeth, become difficult and time-consuming. Patients with bradykinesia have short, shuffling steps on walking or they may find it difficult to get out of a chair. The patient’s speech may be affected and becomes quieter and less distinct. 
• Rigidity (muscle stiffness): In normal cases, muscles stretch when they move, and then relax when they are at rest; however, in patients with Parkinson’s disease, muscles become stiff, inflexible and do not relax, which contributes to limited range of motion. Also, the arms of patients with the diseases usually stop swinging as they walk. Stiffness of the neck, shoulder and legs are common in patients with Parkinson's disease. Rigidity can be uncomfortable or even painful.
• Postural instability: Patients become unstable when standing upright, and may fall backwards if pushed even slightly; this results from the loss of some of the reflexes needed for maintaining an upright posture. Some patients may develop a dangerous condition known as retropulsion, which puts them at the risk of swaying backwards, and even falling, when they rise from a chair, stand or turn around. Difficulties in pivoting or making turns or quick movements are also present in patients who develop balance problems.

• Secondary Motor Symptoms:

• Freezing of gait: The patient may feel that his feet are stuck to the floor. Freezing of gait occurs in certain situations, such as when the patient starts to walk, pivots, crosses a threshold or doorway, and when the patient approaches a chair, but for unknown reasons freezing rarely happens on stairs. Freezing is temporary, and the patient enters a normal stride after first step. Some patients have severe freezing, in which they cannot take a step. Freezing is a potentially serious problem in Parkinson’s disease, as it may increase a patient’s risk of falling forward.
  • Micrographia (writing changes): The patient may have shrinkage in handwriting, this happens as a result of bradykinesia, which causes difficulty with repetitive actions.
  • Mask-like expression: Decreased unconscious facial movements causes affect face expressions in a way that the patient appears less expressive than usual.
  • Unwanted accelerations: Some patients with Parkinson’s disease suffer from unwanted accelerations during speech and movement.
  • Nonmotor Symptoms: Some patients may suffer from symptoms not related to physical tasks or mobility. This includes: 
    • Loss of sense of smell
    • Constipation
    • Mental and behavior disorders
    • Sleep disorders
    • Mood disorders
    • Low blood pressure when standing up

Parkinson’s disease is usually diagnosed based on medical history, detailed discussion of symptoms, and neurological and physical examinations. The doctor may perform a general physical examination using reflex tests, sensitivity to pain or pressure and agility to evaluate, for instance, whether the joints can be moved normally or if the muscles put up resistance.

The best objective testing for Parkinson’s disease consists of specialized brain scanning techniques that can measure the dopamine system and brain metabolism, but these tests are performed only in specialized imaging centers and can be very expensive.

Currently, there are no medications that can cure Parkinson’s disease, but treatments can be useful in controlling the symptoms of the disease and maintaining patient’s quality of life.  

These treatments include:

• Medications

Commonly, the doctor will prescribe different types of medication, including:

• Carbidopa/Levodopa: Levodopa, the most effective medication for Parkinson’s disease, is a natural chemical that is converted into dopamine in the brain to increase its levels. Levodopa is used in combination with carbidopa because it prevents levodopa from being prematurely converted into dopamine in the bloodstream outside the brain, and help reduce its side effects. Levodopa becomes less effective as the disease progresses.

• Dopamine agonists: These stimulate the parts of the brain influenced by dopamine, and imitate its effects in the brain.
• MAO-B inhibitors: This includes selegiline and rasagiline. They work by increasing dopamine levels through inhibiting the brain enzyme monoamine oxidase B (MAO-B) which breaks down dopamine. 
• Catechol-O-methyltransferase (COMT) inhibitors: These are used to prolong the effects of levodopa by blocking an enzyme that metabolize dopamine.  
• Anticholinergics: Benztropine or trihexyphenidyl are two anticholinergics used to help control tremors.  However, their modest benefits are often out-balanced by side effects that include confusion, hallucinations and constipation. 
• Amantadine: Amantadine is usually used alone to provide short-term relief of slight symptoms in early-stage Parkinson’s disease. It can be given with carbidopa-levodopa during the later stages to control involuntary movements induced by carbidopa-levodopa.

• Surgical procedures

There are two surgical procedures that may be performed on patients with Parkinson’s disease: 

• • Deep Brain Stimulation (DBS): Electrodes are inserted into a specific part of the brain. These electrodes convey electrical pulses sent from a generator implanted in the chest to the brain. This may help reduce symptoms of Parkinson’s disease, and can effectively control erratic and fluctuating responses to levodopa and control involuntary movements that do not improve with medication. According to Parkinson’s Disease Foundation, DBS surgery is approved for patients in the initial stages of Parkinson’s disease, for patients who are at least four years into their disease and for patients with motor complications that are not adequately controlled with medication.

• Carbidopa/Levodopa Enteral Suspension (DUOPA ™): This is a gel formulation of the standard drug combination is inserted through a small hole in the abdomen to directly deliver the drugs into the small intestine. Direct delivery of the drugs improves absorption and reduces off-times.  

• Supportive therapies

Several supportive therapies can help make life easier for patients with Parkinson’s disease. These supportive therapies include: 

• Physiotherapy: Physiotherapy helps relieve muscle stiffness and joint pain in patients with Parkinson’s disease through exercise. Additionally, physiotherapy helps make the patient's movement easier, improves their walking and flexibility, and improves their fitness level and ability to manage things by themselves.
• Occupational therapy: Occupational therapy can help patients with Parkinson’s disease determine and resolve areas of difficulty in their daily life, and ensure that their homes are properly set up, and give them practical solutions to maintain their independence. 
• Speech and language therapy: Usually, patients with Parkinson’s disease suffer from swallowing difficulties, and problems with their speech. Practicing speech and swallowing exercises, or using assistive technology provided by speech and language therapists can help solve these problems.

•  Dietary changes

Some dietary practices are useful in managing the symptoms of the disease. Dietary changes need to be discussed with patient’s doctor to avoid unwanted complications:

• •  Eating a diet high in fiber and consuming sufficient amounts of water and fluids can reduce constipation. 
  • Small frequent meals with an increase in salt intake can help in controlling blood pressure.
  • Monitoring body weight to avoid unexpected weight loss.

In addition to motion difficulties, tremors in Parkinson’s disease can initiate several non-motor problems that have physical and emotional influences on patients and their families. These include: 

• Swallowing difficulties:  Loss of control of throat muscles, and impaired chewing and swallowing are associated with the progression of the disease. Saliva may accumulate in the mouth due to decelerated swallowing, leading to drooling.
• Emotional and behavioral changes: The progression of the diseases itself may lead to emotional and behavioral changes due to alterations in brain chemicals that affect mood and well-being and may lead to depression. Some drug treatments (levodopa combined with a dopamine agonist) can cause compulsive behaviors, such as gambling, shopping, and increased sexuality. Anxiety, fear, and loss of motivation are also common in patients with Parkinson’s.

• Cognitive and Memory Problems: These problems occur either directly from the effects of the disease, or from side effects of medications used to treat it.
• Sleep Disorder: Excessive daytime sleepiness, insomnia, waking up frequently at night, waking up early or falling asleep during the day are sleep problems common in patient with Parkinson’s disease.
• Sexual dysfunction: Parkinson’s disease treatments can cause compulsive sexual behavior, but the disease can cause loss of sexual desire or performance in both men and women. Erectile dysfunction can be a complication of Parkinson’s disease in men.
• Bowel and Bladder problems: constipation is common in patients with Parkinson’s disease due to muscle weakness that can slow the digestive system. Parkinson’s disease may also lead to urinary incontinence, including increased urge and frequency, and the inability to control urine or having difficulties initiating urination.
• Sensory Problems: This includes impaired sense of smell and vision problems.
• Fatigue: The cause of fatigue isn't always known in patients with the disease.
• Pain: Patients with Parkinson’s disease experience pain, numbness, and tingling either in a specific area of the body or throughout.

The prevention strategies of Parkinson’s disease are unknown, because the direct cause of Parkinson’s disease is unknown. However, caffeine which is found in coffee and tea and green tea may reduce the risk of developing Parkinson’s disease. Doing aerobic exercises regularly may reduce the risk of Parkinson's disease.

Parkinson’s disease is not a fatal disease, but it can decrease longevity. The disease develops faster in older patients and may cause severe disability within 10 - 20 years. Also, older patients tend to have more muscle freezing and greater diminishing in mental and daily functions. If the tremor appears as an early sign of the disease, the patient’s health status is likely to be less severe than if the tremor had not been present.

The way Parkinson’s diseases progresses and the rate at which it does is different from person to person, i.e. some patients may become severely disabled, while others only experience minor motor symptoms.

 The disease progresses from mild to moderate and then to severe, but the disease never advances to become severe in many patients. The stages if Parkinson’s disease are:

Mild Parkinson’s disease

• Motor symptoms are apparent, but do not affect daily activities. 
• Motor symptoms usually happen on one side of the body. 
• The patient’s posture, walking ability or facial expressions is changed. 
• Regular exercises improve and maintain mobility, flexibility, range of motion and balance. 

 Moderate Parkinson’s disease

• Both sides of the body are affected with motor symptoms. 
• Body movement becomes slower. 
• Balance and coordination problems are present. 
• Freezing may occur. 
• Regular exercises and physical therapy help maintain good mobility and balance.
• The patient can maintain independence through occupational therapy. 

Severe Parkinson’s disease

• Serious walking difficulties.
• All daily activities need help to be performed.
• Prominent cognitive problems.

The Parkinson’s Disease Foundation estimates that more than 10 million people are living with Parkinson's disease worldwide. Parkinson’s disease is more common in men by one and a half times. Incidence of Parkinson’s disease increases with age, but an estimated 4% of people with Parkinson’s disease are diagnosed before the age of 50.