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- Parkinson disease (PD) is a progressive neurodegenerative disorder caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta.
- Cardinal symptoms include resting tremor, rigidity, bradykinesia, and postural instability.
- Diagnosis is based primarily on history and examination.
- Average age of onset: ~60 years
- Slightly more common in men than women
- Second most common neurodegenerative disease after Alzheimer disease
- 0.3% of general population and 1–2% of those ≥60 years of age and up to 4% of those ≥80 years of age
- Affects approximately 1 million people in the United States and 5 million worldwide
Etiology and Pathophysiology
Dopamine depletion in the substantia nigra and the nigrostriatal pathways results in the major motor complications of PD.
- Pathologic hallmark: selective loss of dopamine-containing neurons in the pars compacta of the substantia nigra
- Loss of neurons accompanied by presence of Lewy bodies, pale bodies (predecessor of the Lewy body), and Lewy neuritis
Mutations in multiple autosomal dominant and autosomal recessive genes have been linked to PD/parkinsonian syndrome particularly when the age at symptom onset is <50 years. Genes investigated in PD include SNCA, Parkin, PINK1, DJ-1, and LRRK2.
- Age and family history of PD or tremor are the greatest risk factors.
- History of smoking as well as coffee and caffeine intake may reduce risk.
- Weak association with exposure to toxins (herbicides and insecticides); however, relationship is not clear.
Commonly Associated Conditions
Non–motor-associated symptoms include cognitive abnormalities, autonomic dysfunction (e.g., constipation, urinary urgency), sleep disturbances, mental status changes (depression, psychosis, hallucinations, dementia), orthostatic hypotension, and pain.