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Parkinson's disease (PD) is the second commonest neurodegenerative disease, exceeded only by Alzheimer's disease (AD). It is estimated that approximately 1 million persons in the United States and 5 million persons in the world suffer from this disorder. PD affects men and women of all races, all occupations, and all countries. The mean age of onset is about 60 years, but cases can be seen in patients in their 20s, and even younger. The frequency of PD increases with aging, and based on projected population demographics, it is estimated that the prevalence will dramatically increase in future decades.

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Clinically, PD is characterized by rest tremor, rigidity, bradykinesia, and gait impairment, known as the “cardinal features” of the disease. Additional features can include freezing of gait, postural instability, speech difficulty, autonomic disturbances, sensory alterations, mood disorders, sleep dysfunction, cognitive impairment, and dementia (Table 372-1), all known as nondopaminergic features because they do not fully respond to dopaminergic therapy.

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Table 372-1 Clinical Features of Parkinson's Disease
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Pathologically, the hallmark features of PD are degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), reduced striatal dopamine, and intracytoplasmic proteinaceous inclusions known as Lewy bodies (Fig. 372-1). 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 nondopaminergic clinical features listed in Table 372-1. Indeed, there is evidence that pathology begins in the peripheral autonomic nervous system, olfactory system, and dorsal motor nucleus of the vagus nerve in the lower brainstem, and then spreads in a sequential manner to affect the upper brainstem and cerebral hemispheres. These studies suggest that dopamine neurons are affected in midstage disease. Indeed, several studies suggest that symptoms reflecting nondopaminergic degeneration such as constipation, anosmia, rapid eye movement (REM) behavior sleep disorder, and cardiac denervation precede the onset of the classic motor features of the illness.

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