Parkinson's disease

Parkinson's disease is a slowly worsening disorder of the nervous system and the most common cause of parkinsonism, a recognizable pattern of movement problems. Its central damage is the death of neurons in a midbrain region called the substantia nigra, whose cells supply dopamine to the basal ganglia, the circuits that help start and smooth movement. By the time symptoms appear, most of these neurons are already gone. Surviving brain cells often contain Lewy bodies, clumps of the protein alpha-synuclein, and neurons that make norepinephrine are lost too.

The core signs are a resting tremor that often starts in one hand, rigidity, slowness of movement (bradykinesia) and, later, poor balance. Many people also have problems unrelated to movement, such as loss of smell, constipation, sleep disturbances, low blood pressure on standing, depression and eventually memory and thinking difficulties. Onset is usually after 60. In most people the cause is unknown; some cases run in families, and variants in genes such as LRRK2, SNCA, PRKN and GBA1 can cause the disease or raise risk.

Diagnosis is mainly clinical, sometimes aided by a dopamine transporter scan or alpha-synuclein tests. No treatment halts it, but levodopa, which the brain converts to dopamine, and dopamine agonists ease movement symptoms, and deep brain stimulation can help when drugs work less well.