admin | 
02 10th, 2008| 
Abstract
Behavioral and psychiatric problems associated with idiopathic Parkinson’s disease (PD) include cognitive dysfunction, drug-related psychosis, depression, anxiety, apathy, fatigue and sleep disturbance. These nonmotor symptoms are a significant cause of disability at all stages of illness. Cognitive dysfunction spans a continuum from circumscribed cognitive impairments to severe global dementia which can occur in up to 10±30% of advanced PD patients. Psychosis develops in 20±30% of PD patients receiving chronic antiparkinsonian therapy.
Visual hallucinations and paranoid delusions are the most frequent symptoms. The gradual elimination of drugs of lesser priority that may affect cognition and/or cloud the sensorium constitutes the first step in the management of cognitive and psychotic symptoms. Atypical neuroleptic agents are an invaluable tool in those cases in which maximum drug regimen simplification is not adequate or results in unacceptable immobility. Depression and anxiety often go unrecognized although they are eminently treatable and may be important contributors to the morbidity of PD. They are present in 30±40% of PD patients and frequently occur together in association with other nonmotor symptoms such as apathy, fatigue and sleep disturbance. A combination of early recognition, counseling, antidepressant therapy, antianxiety and well-balanced antiparkinsonian therapy sets the stage for improved quality of life for patients with PD.
1. Introduction
There are a wide range of behavioral disturbances associated with idiopathic Parkinson’s disease (PD) including depression [1], anxiety [2], fatigue [3], sleep disturbances [4], cognitive dysfunction [5,6] and drug-related psychosis [7]. Collectively these symptoms affect the majority of patients with PD [1-7]. While PD is traditionally described as a motor disorder, there is increasing awareness that the behavioral non-motor symptoms constitute an important source of disability. Early recognition and effective management of the non-motor symptoms of PD is integral to the quality of life of both patients and caregivers [8]. We will review the current knowledge in this expanding field, focusing on the practical issues involved in the delicate balance of managing both motor and non-motor symptoms in PD.
2. Cognitive dysfunction
Cognitive dysfunction in Parkinson’s disease (PD) spans a continuum that ranges from circumscribed cognitive impairments that may be observed relatively early in the disease process to global dementia in the late stages of the disease. Although estimates vary, dementia occurs in 10±30% of advanced PD patients [5,6,9], while more discrete cognitive impairments not only occur earlier, but also, affect the large majority of patients. These cognitive changes may not be fully appreciated if targeted testing with a broad neuropsychological battery is not performed [10].
The age standardized ratio of dementia in PD patients compared to controls was 4.6 in a recent study conducted in France [11]. Mayeux et al. [12] in a re-evaluation of the clinic-based sample 5 years after his prevalence analysis [10], indicated that the incidence of dementia was 69 per 1000 person years of observation, which was almost 6 times that expected in an aged-matched cohort.
Several risk factors have been associated with the development of dementia in PD including older age at the onset of PD [10,11,13], severity of extrapyramidal signs, especially bradykinesia [14,15], family history of dementia [16,17], depression [13,14,18], psychological stress [19] and low socioeconomic or educational attainment [20].
Cognitive dysfunction in PD is primarily attributed to defects of subcortical processing as opposed to cognitive impairment in Alzheimer’s disease (AD) which is attributed to cortical dysfunction [21]. The dementia associated with PD is characterized by impairment of executive functions (e.g. planning, sequencing, monitoring and shifting between responses), visuomotor skills, visuospatial skills, free recall of both verbal and nonverbal material and verbal fluency. Cortical functions such as praxis, calculations, orientation, cued recall, recognition memory and certain other aspects of language are relatively spared [22]. Perhaps the main distinguishing factor between patients with PD and those with AD is performance on delayed recall as compared to immediate recall. PD is characterized by relatively good retention of ewly acquired information following a delay, while patients with AD tend to rapidly forget it. This supports he belief that the memory impairment associated with PD is primarily a retrieval deficit as opposed to AD, which is characterized by deficient encoding or consolidation of information. The poor retrieval of new information by PD patients may be secondary to a form of executive dysfunction, consisting of the inability to initiate a systematic search of memory, reflecting a dysfunction of subcorticofrontal circuits [23].
The relatively circumscribed cognitive problems seen in many PD patients may or may not progress to global dementia [22]. Risk factors associated with the development of dementia were previously described. Additional neuropsychological predictors of later decline have also been identified including the individual’s performance on tests of letter, category and verbal fluency [24,25]. The progression of the milder and more circumscribed cognitive deficits seen in many PD patients towards more global impairments appears to represent not only a quantitative change but also, a qualitative shift in the pattern of cognitive domainsinvolved [26]. This concept is supported by neuropathological evidence of damage extending beyond the dopaminergic system in PD patients with advanced dementia [27,28].
3. Drug-related psychosis
Drug-related psychosis occurs in 20±30% of PD patients following chronic antiparkinsonian therapy [36]. The mechanisms responsible for its appearance are not well understood but dopaminergic (especially mesolimbic) and serotoninergic systems are likely to be involved [36].
Almost all of the drugs used to treat PD may induce psychosis although individual patients commonly demonstrate particular sensitivity to individual medications. The emergence of drug related psychotic ideation requires careful monitoring since this problem can be severely disabling and is more likely to lead to nursing home placement than either motor dysfunction or dementia [37]. In addition, there is a marked increase in the mortality rate of PD patients with drug-related psychosis [38].