The neuropsychiatry of Parkinson's disease and related disorders

Epidemiological, neuropathological, radiological, and clinical features of Parkinsonian neurodegenerative diseases are reviewed, including synucleinopathies and four-repeat tauopathies. Parkinson's disease (PD) is associated with dementia, depression, anxiety, sexual dysfunction, and dopamine agonist-related psychosis and mania. Delirium may result from secondary complications of PD, drug treatment, or withdrawal of dopamine agonists. Psychosis is a key factor in nursing home placement, while depression and cognitive impairment are critical predictors of quality of life. Clozapine is effective against psychotic features, but optimal antidepressant therapy awaits definition. Dementia with Lewy bodies (DLB) presents with early frontal dementia, cognitive fluctuations, and well-formed visual hallucinations, often attended by falls, syncope, systematized delusions, neuroleptic intolerance, depression, and rapid eye movement (REM) behavior disorder (RBD). Early evidence suggests the utility of rivastigmine, donepezil, and low-dose olanzapine and quetiapine in DLB. Multiple system atrophies (including striatonigral degeneration, Shy-Drager syndrome, and olivopontocerebellar atrophy) are typified by poor levodopa response, dysautonomia, ataxia, frontal cognitive impairments, RBD, sleep apnea, and depression. Progressive supranuclear palsy is associated with early backward falls, slow vertical saccades, impaired downgaze, subcortical dementia, apathy, pathological emotionality, mild depression and anxiety, and poor response to dopamine agonists and donepezil. Cortico-basal ganglionic degeneration presents with multiple unilateral movement disorders, early frontal dementia, apraxias, alien limb, personality changes, and depression. FTDP-17 presents with frontotemporal dementia, Parkinsonism, personality changes, and sometimes hyperorality or psychosis. Parkinson's disease (PD) is one of a number of neurodegenerative disorders in which abnormal proteins are found. Among neurodegenerative proteinopathies in which Parkinsonism occurs are the alpha-synucleinopathies and tauopathies. alpha-synucleinopathies include PD, dementia with Lewy bodies (DLB), and the multiple system atrophies (MSA), diseases in which alpha-synuclein is found in intraneuronal or intraglial inclusions. Tauopathies involve the elaboration of abnormal tau protein and include progressive supranuclear palsy (PSP), Cortico-basal ganglionic degeneration (CBD), and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). Alzheimer's disease (AD) is another tauopathy, but unlike the aforementioned, it also involves the production of abnormal P-amyloid protein. Parkinsonian features also may be observed in conjunction with other neurodegenerative proteinopathies, including prion proteinopathies such as Creutzfeldt-Jakob disease and Gerstmann-Straussler-Sheinker disease, in which rigidity occurs; the superoxide dismutase proteinopathy amyotrophic lateral sclerosis (ALS), wherein ALS may be associated with Parkinsonism and dementia, as on the island of Guam; and the childhood form of the polyglutamine expansion proteinopathy Huntington's disease, where Parkinsonian features including rigidity are associated with psychosis and bipolar disorders. This article considers the neuropsychiatric manifestations occurring in Parkinsonian disorders. Because Parkinsonian features are incidental to the primary disease, or the neuropsychiatry remains in need of definition in some of these illnesses, this article focuses on the neuropsychiatry of PD, DLB, MSA, PSP, CBD, and FTDP-17.