Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android


Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease, exceeded only by Alzheimer’s disease (AD). Its cardinal clinical features were first described by the English physician James Parkinson in 1817. It is noteworthy that James Parkinson was a general physician who captured the essence of this condition based on a visual inspection of a mere handful of patients, several of whom he only observed and did not formally examine. It is estimated that the number of people with PD in the most populous nations worldwide was ~4 million persons in 2005, and this number is expected to more than double to ~9 million by the year 2030 based on the aging of the population. The mean age of onset of PD is about 60 years, and the lifetime risk is ~2% for men and 1.3% for women. The frequency of PD increases with aging, but cases can be seen in individuals in their twenties and even younger, particularly in association with a gene mutation.

Clinically, PD is characterized by rest tremor, rigidity (stiffness), bradykinesia (slowing), and gait dysfunction with postural instability. These are known as the “cardinal features” of the disease. Additional clinical features can include freezing of gait, speech difficulty, swallowing impairment, autonomic disturbances, and a series of nonmotor features that include sensory alterations, mood disorders, sleep dysfunction, cognitive impairment, and dementia (see Table 427-1 and discussion below).

TABLE 427-1Clinical Features of Parkinson’s Disease

Pathologically, the hallmark features of PD are degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), reduced striatal dopamine, and intraneuronal proteinaceous inclusions known as Lewy bodies and Lewy neurites that primarily contain the protein α-synuclein (Fig. 427-1). While interest has primarily focused on the dopamine system, neuronal degeneration with inclusion body formation can also affect cholinergic neurons of the nucleus basalis of Meynert (NBM), norepinephrine neurons of the locus coeruleus (LC), serotonin neurons in the raphe nuclei of the brainstem, and neurons of the olfactory system, cerebral hemispheres, spinal cord, and peripheral autonomic nervous system. This “nondopaminergic” pathology is likely responsible for the development of the nondopaminergic clinical features listed in Table 427-1. There is some evidence that Lewy body pathology can begin in the peripheral autonomic nervous system, olfactory system, and dorsal motor nucleus of the ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.