Parkinson’s disease, first described by James Parkinson in 1817, is caused by an idiopathic degeneration of subcortical structures, primarily the substantia nigra. Structural damage and subsequent dopaminergic dysfunction result in significant motor abnormalities, mood disturbance, and dementia in some patients. While the biological basis of dementia in Parkinson’s disease remains unclear, the degeneration of the nucleus basalis of Meynert may contribute to cognitive impairment. The typical age of onset of Parkinson’s disease is between 50 and 60 years old, although variants may occur between one and two decades earlier. Dementia in Parkinson’s disease occurs in approximately 20 to 30 percent of patients and typically affects frontal lobe executive functioning and memory. Nondemented patients also demonstrate milder cognitive deficits in visuospatial and attention shifting tasks. Neuropathology confirms the diagnosis of Parkinson’s disease and is characterized by intracytoplasmic inclusions, Lewy Bodies, in the substantia nigra.
The hallmark of Parkinson’s disease is a movement disorder characterized by tremor, bradykinesia, and rigidity. The tremor occurs at rest bilaterally or unilaterally, and may appear ‘pill-rolling’ in nature. Bradykinesia is manifested by a slow and shuffling gait, blunted affect, monotonous speech, and difficulty in the initiation and execution of movement. Rigidity may also be bilateral or unilateral and is described as cogwheel rigidity, with stiffness and a superimposed jerkiness throughout flexion and extension. Depressive symptoms are a common feature of Parkinson’s disease, occurring in up to 50% of patients. Depressive symptoms may be related to the on-off phenomena associated with dopamine agonist treatment, where mood symptoms worsen during the ‘off’ period coincident to changes in motoric function, and abate in the ‘on’ period. The depressive syndrome associated with Parkinson’s disease is typically characterized by dysphoria, irritability, hopelessness, and suicidal ideation. Psychomotor retardation is a common finding that may be associated with both the major depression and the cognitive and motor impairments of the primary disease. Psychotic symptoms have also been reported in the context of depressive episodes, or as the consequence of dopamine agonist treatment.
The treatment of Parkinson’s disease typically includes dopamine precursors such as levodopa or the combination of levodopa and carbidopa. The symptoms of bradykinesia and rigidity tend to be more responsive than tremor to dopaminergic agents. Second-line agents for motor dysfunction include dopamine agonists such as pergolide or bromocriptine, and anticholinergic medications such as benztropine. Selegeline, a monoamine oxidase type B inhibitor, has been shown to slow the progression of motor impairment. Randomized controlled trials with donepezil also support its use for the treatment of cognitive symptoms. Future directions of research include newer dopamine agonists, coenzyme Q, surgical treatment, and fetal neural tissue transplantation. Comorbid major depressive disorder should be treated with standard antidepressant medications and ECT. ECT may temporarily improve the motor symptoms of PD, as well.