## EPIDEMIOLOGY

Key Clinical Questions

• Does the patient meet diagnostic criteria for idiopathic Parkinson’s disease (PD)?

• What is the differential diagnosis of a patient with parkinsonian symptoms?

• What is the pathophysiology of Parkinson’s disease?

• What treatments are available, and how do they relate to the underlying pathophysiology?

• What are the short- and long-term side effects that may occur in a PD patient on medication?

• What are typical complications that may occur when a PD patient is admitted to the hospital?

Parkinson’s disease (PD) appears in 12 to 20/100,000 people per year, approaching a prevalence of 1 in 2000 people. Quality of life can be markedly affected due to a wide variety of factors, some of which have only recently been recognized, such as autonomic dysfunction.

The economic burden of Parkinson’s disease is high. On average, $4000 to$5000 can be spent per patient/year, and of that amount, roughly 33% to 40% may be indirect costs, such as lost productivity. On average, PD-affected patients are unable to work full time 3.4 years after diagnosis, and most file for disability by 5 years. In addition, having PD is a risk factor for nursing home placement.

## PATHOPHYSIOLOGY

Parkinson’s disease is caused by the loss of midbrain dopaminergic neurons in the substantia nigra pars compacta (SNc). How dopamine loss disrupts normal functioning of the basal ganglia is not fully understood, but it appears to result in pathological synchronization of neuronal firing throughout the region, which interferes with the production of both voluntary and involuntary movements.

Parkinson’s disease also has many nonmotor symptoms, with effects on cognition, behavior, and sleep. There is emerging evidence of a more widespread neurodegenerative process in PD, affecting brainstem, midbrain, and cortical structures, and probably involving neurotransmitters other than dopamine.

In most cases, the cause of PD is unknown. Mutations of genes associated with PD, such as parkin, DJ-1, GBA, and LRRK2, have recently been identified, although these still make up a minority of cases. The relationship of these mutations to dopaminergic neuron death is not known.

The pathological hallmark of PD is the presence of Lewy bodies in the neurons of the SNc. These are intracellular clumps of proteins, which include alpha-synuclein, ubiquitin, and others. Alpha-­synuclein is thought to be a phospholipid-binding protein that helps vesicles dock with the plasma membrane. It is not known whether these inclusion bodies kill the neurons in which they develop, or more likely, whether they represent a “waste-basket” keeping damaged proteins out of the way of normal cellular functioning. In addition to being found in the brainstem, particularly in the SNc, in PD, Lewy bodies can be more widely distributed, and are found specifically in the cortex in the related disorder known as dementia with Lewy bodies (see below).

Patients who are early in their clinical course of PD have ...

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