| Parkinson's DiseaseDefinition - Idiopathic Parkinson’s disease (PD): the most common of the progressive neurodegenerative disorders that are characterized by the clinical features of parkinsonism
- A paucity and slowness of movement (bradykinesia)
- Tremor at rest
- Muscular rigidity
- Shuffling gait
- Postural instability
- Although defined clinically as a movement disorder, PD can also be accompanied by a variety of non-motor symptoms, including autonomic, sensory, sleep, cognitive, and psychiatric disturbances.
- Pathologically, PD is characterized by a loss of dopaminergic cells in the substantia nigra and neuronal accumulation of α-synuclein.
 Epidemiology - Incidence of PD
- ~1 million individuals in the U.S.
- ~1% of individuals older than 55 in the U.S. have PD.
- Age
- Only ~1% of patients with PD are < 50 years.
- Peak onset is in the early sixties (range: 35–85 years).
- Sex
Risk Factors - Risk factors for PD
- Positive family history
- Male sex
- Head injury
- Consumption of well water
- Rural living
- Exposure to certain neurotoxins (e.g., carbon monoxide, manganese, some pesticides)
- Reduced risk for PD
- Coffee drinking
- Smoking
- Use of NSAIDs
- Estrogen replacement in postmenopausal women
Etiology - Nearly all forms of parkinsonism result from:
- Reduction of dopaminergic transmission within the basal ganglia
- Accumulation of eosinophilic intraneural inclusion granules (Lewy bodies)
- Widespread involvement of brainstem, olfactory, thalamic, and cortical structures explains physiologic basis of non-motor signs and symptoms.
- More than 75% of parkinsonism is sporadic and idiopathic (PD).
- Less than 25% of parkinsonism is of genetic or other etiology (i.e., other neurodegenerative disorders, cerebrovascular disease, and drugs)
- Mutations in multiple different genes cause familial forms of parkinsonism (PARK1 though PARK10); α-synuclein mutation (PARK1) or extra copy of this gene (PARK4) among genetic etiologies
- Heredity plays more important role if age of onset is < 45 years.
Associated Conditions - Disturbances of behavior, mood, and cognition commonly accompany PD, especially in its later stages.
- In some, may be the result of comorbid pathologies (e.g., dementia with Lewy bodies, Alzheimer’s disease)
- Impulse control disorders
- These insidious behavioral disturbances occur in a subset of patients with PD and include pathologic gambling, hypersexuality, compulsive shopping, compulsive eating, and stereotypical motor behaviors with repetitive handling and examining of mechanical object.
- These conditions are also associated with the use of dopaminergic therapy, especially dopamine agonists.
- Current therapeutic approaches include:
- Reduction or discontinuation of dopamine agonist therapy
- Psychosocial interventions
- Deep brain stimulation (DBS)
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