Parkinson disease: Not just a movement disorder
ABSTRACTNonmotor symptoms are common in Parkinson disease and can significantly worsen the health and quality of life of the patient and family members. These symptoms can be broadly categorized as sensory, autonomic, cognitive-behavioral, and sleep-related. Clinicians can improve the care of these patients by recognizing and addressing these problems.
KEY POINTS
- Nonmotor symptoms can be due to the disease itself, to its treatment, or to on-off fluctuations in motor status as doses of medication wear off.
- Impaired sense of smell, depression, anxiety, fatigue, and constipation can precede the motor symptoms of Parkinson disease and may be symptoms of the disease itself.
- Orthostatic hypotension, sedation, psychosis, confusion, and impulsiveness may be adverse effects of medical therapy or may worsen with it.
- Depression occurs in up to 50% of patients with Parkinson disease, although it may be difficult to recognize because many of its physical features can also be manifestations of Parkinson disease itself.
Apathy
Apathy is present in approximately 30% of patients with Parkinson disease.46
Apathy can be very difficult to differentiate from depression, as the two disorders can occur together. Apathy can also be present without signs or symptoms of depressed mood. Apathy is commonly conceptualized as involving three domains: cognitive (lack of interest), behavioral (lack of initiation and drive), and affective (lack of emotion). The possibility of a primary apathy syndrome should be considered if the patient does not respond to standard treatments for depression. This is critical, as the treatment of the two syndromes may differ.47
Although efficacy data are limited, bupropion (Wellbutrin) and methylphenidate (Ritalin)48 can be tried for their activating or stimulant properties.
Anxiety disorders
Anxiety disorders commonly accompany depression in Parkinson disease, but they can also occur independently. They most often present in the setting of wearing-off or on-off fluctuations associated with medication status. Anxiety disorders in patients with Parkinson disease include generalized anxiety and panic attacks, which are responsive to SSRIs and benzodiazepines.49 Benzodiazepines are effective, and clonazepam (Klonopin) may be preferred because it has a long half-life, thereby minimizing anxiety associated with wearingoff or unpredictable off periods. Conversely, a long half-life and depressive effects may limit its use in advanced age.
Classic obsessive-compulsive disorder is less common, but obsessive behaviors and impulse control difficulties can occur in up to 7% of patients with Parkinson disease and presumably reflect dopamine dysregulation, most often associated with dopamine agonists.50 Impulsive behavior can include gambling, hypersexuality, and bingeing.
One form of obsessive-compulsive disorder is punding, a behavior characterized by intense fascination with repetitive handling and examining of objects, most often mechanical objects.51 Behaviors can include assembling and disassembling, collecting, or sorting of objects.
Visual hallucinations
Many patients with Parkinson disease have visual hallucinations as a side effect of dopaminergic drugs. At first, the patient realizes that they are hallucinations, but this insight may be lost as the disease progresses. The clinician should also consider other potential causes such as dementia, systemic illness, or psychosocial stress.
If visual hallucinations present early in the course of the disease and are accompanied by loss of insight and by cognitive fluctuations, the patient may actually have Lewy body dementia.52 Its features include parkinsonian symptoms, visual hallucinations, a fluctuating level of consciousness, and neuroleptic sensitivity.
Psychosis
The first-line treatment for psychosis in patients with Parkinson disease should involve:
- Searching for a systemic illness such as urinary tract infection, aspiration pneumonia, or dehydration;
- Stopping or lowering the dose of drugs that act on the central nervous system; and
- If possible, stopping or lowering the dose of anti-Parkinson drugs that have the greatest risk of cognitive side effects. In many cases, this is not a realistic option, and adding an antipsychotic drug may be necessary.
Monitoring and treating psychosis is paramount, as it is a major risk factor for nursing home placement.53
Conventional neuroleptics such as haloperidol (Haldol) should be avoided because they can exacerbate parkinsonian symptoms.
Two atypical neuroleptics, clozapine (Clozaril) and quetiapine (Seroquel), appear to be the best tolerated in Parkinson disease patients. Clozapine is the only neuroleptic found to be more efficacious than placebo in patients with Parkinson disease.54 However, of the two, clozapine has a higher risk of side effects and requires frequent blood monitoring, making it difficult to use. Quetiapine has been shown to be as efficacious as clozapine,55 but it failed to show efficacy in a recent controlled study.56 Nevertheless, it is considered the first-line treatment option, since it is safer.40
Other atypical antipsychotics appear to exacerbate Parkinson disease or have not been adequately studied and should therefore be used with caution.
Dementia
Estimates of the prevalence of dementia in patients with Parkinson disease vary widely, most likely reflecting differences in populations studied and methods used. The best estimates indicate that 20% to 30% of patients with Parkinson disease develop dementia.57
Parkinson dementia is one of the classic subcortical dementias, characterized by slow thinking and by difficulties in working memory and problem-solving due to disruption of frontal-subcortical circuits.58 Its most common neuropsychiatric symptoms are hallucinations and depression, with less agitation, disinhibition, and irritability than in Alzheimer dementia.59
Anti-Parkinson drugs, especially anticholinergics, can exacerbate cognitive impairments in patients with Parkinson disease. An acute change in cognitive abilities or visual hallucinations is often associated with an un derlying medical illness such as infection (eg, a urinary tract infection or aspiration pneumonia) or dehydration.
Anticholinesterase inhibitors such as rivastigmine (Exelon) are indicated in patients with Parkinson dementia but may provide only a modest benefit.60
