Parkinson's Disease

Tanner, Caroline M. M.D., Ph.D.
Ostrem, Jill L. M.D.

From the Movement Disorders and Neuromodulation Center, Department of Neurology, Weill Institute for Neuroscience, University of California, San Francisco, San Francisco.

Dr. Tanner can be contacted at [email protected] or at the Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, 1651 4th St., Box No. 1838, Weill Institute Bldg., San Francisco, CA 94158.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Allan H. Ropper, M.D., Editor

New England Journal of Medicine 391(5):p 442-452, August 1, 2024. | DOI: 10.1056/NEJMra2401857

Key Points

Parkinson's Disease

Parkinson's disease is a progressive disorder of later life, defined clinically by motor features (asymmetric bradykinesia, rigidity, tremor, and imbalance) and pathologically by neuronal degeneration and intraneuronal misfolded α-synuclein (Lewy bodies) in specific central and peripheral nervous system regions, including dopaminergic brain-stem neurons.
Disorders of mood, sleep, sensation, cognition, and autonomic function are common, often preceding motor signs by years (prodromal Parkinson's disease) and increasing with the duration of the disease.
Gene variants are causative in approximately 20% of cases. Nongenetic risk factors that increase risk (toxicants and head injury), plus small contributions of common variants, probably cause most cases. Exercise may decrease risk.
No therapy has been proved to slow progression. Dopaminergic therapies improve motor function, but loss of efficacy and side effects are common. Deep-brain stimulation surgery is effective for motor fluctuations.
Nonmotor symptoms cause substantial morbidity, but evidence for treatment is sparse. Off-label medications are commonly used. Comprehensive multidisciplinary care is helpful.
Biomarker research suggests that a biologic definition of Parkinson's disease is possible.

Parkinson's Disease

Parkinson's disease is a multisystem neurodegenerative disorder with motor and prominent, sometimes premonitory, nonmotor symptoms. Detection of gene variants may inform prognosis and, potentially, treatment.