Description

• Parkinson disease (PD) is a progressive neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra pars compacta as well as other dopaminergic regions of the brain.
• Cardinal symptoms include resting tremor, rigidity, bradykinesia, and postural instability.
• Diagnosis is primarily clinical.

Epidemiology

• 8 to 18.6 per 100,000 person-years
• Average age of onset: ~60 years
• Slightly more common in men than women

• Second most common neurodegenerative disease after Alzheimer disease
• 3.3/1,000 persons
• 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 (hyaline inclusion bodies) and Lewy neuritis

Genetics
Mutations in multiple autosomal dominant and autosomal recessive genes are 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.

Risk Factors

• Age and family history of PD or tremor. Weak association with exposure to toxins (herbicides and insecticides); relationship is not clear.
• Repeated head trauma and living in rural areas, drinking well water, working in a wood pulp mill
• History of smoking as well as coffee and caffeine intake may reduce risk.

Commonly Associated Conditions

Cognitive abnormalities, autonomic dysfunction (e.g., constipation, urinary urgency), sleep disturbances, mental status changes (depression, psychosis, hallucinations, dementia), orthostatic hypotension, and pain