Cognitive and Mood Disorders in Parkinson s Disease Video Transcript

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1 Cognitive and Mood Disorders in Parkinson s Disease Video Transcript This is the first of two videos describing non-motor symptoms of Parkinson s disease. In this video we discuss cognitive and mood disorders as they relate to Parkinson s disease. Depression is remarkably common in patients with Parkinson s disease and will affect up to 50 percent of patients at some time in their disease. Depression is a strong contributor to reduced quality of life and aggressive treatment can improve this. Symptoms include fatigue, weight gain or weight loss due to an increase or decrease in appetite, sadness, and reduce concentration. The progressive degeneration of different brain systems, especially those affecting the norepinephrine and serotonin systems, combined with the disability associated with Parkinson s disease, are strong contributors to the cause of depression.

2 There are several effective treatments for depression including psychotherapy and medication. Exercise has been shown to improve fatigue and improve mood. So in addition to performing exercise to help motor symptoms, exercise can also help certain nonmotor symptoms. There have been controlled trials of various antidepressants in patients with Parkinson s disease demonstrating significant improvement. These antidepressants include paroxetine, which is an example of a selective serotonin reuptake inhibitor; venlafaxine, which is an example of a serotonin norepinephrine reuptake inhibitor; and nortriptyline, which is a tricyclic antidepressant. Interestingly, the dopamine agonist, pramipexole, has also been shown to improve depression symptoms suffered from its effect on motor symptoms and so may be used to treat both problems. As with depression, anxiety is remarkably common. It may exist by itself or may be seen in combination with depression. Anxiety can be chronic in persistent problems, but it is often worsened in patients with motor fluctuations during the medication-off state when there is worsening of motor symptoms. A variety of medications including

3 benzodiazepines or Valium-type medications in addition to antidepressants may be helpful. Psychotherapy and learning anxiety reduction techniques may also be helpful. Apathy refers to lack of motivation or reduced interest in activity. It is important to determine out whether or not apathy is present by itself or is a symptom of depression. If depression is present, treating the underlying depression may be helpful. Specific treatment paradigms for apathy in Parkinson s disease otherwise have not been fully developed. Behavioral interventions or treatment with stimulants or dopamine agonists might be helpful based on the utility of these treatments in other diseases where apathy is present. Impulse control disorder refers to excessive or inappropriate interest in certain activities. These activities are vegetative or basic drives. The inappropriate interests include pathologic gambling, hypersexuality, excessive interest in certain hobbies, binge eating, compulsive shopping, or internet addiction. Usually, these problems are caused by the use of dopamine agonist medication such as pramipexole, ropinirole, and

4 rotigotine. Often the patient may have poor awareness of the inappropriateness and excessive nature of these activities and the caregiver or spouse may be most aware of these problems. Impulse control disorder may affect up to 17 percent of patients treated with dopamine agonists. Risk factors include being male, being younger in age, being unmarried, and having a personal or family history of drug or alcohol use. Usually, the dopamine agonist dose must be reduced, and often the medication needs to be completely stopped in order to improve these symptoms. A small percentage of patients may have difficulty completely withdrawing from dopamine agonists and this is referred to as dopamine agonist withdrawal syndrome, which can be a chronic problem of drug craving that may not be resolved even with an increase in levodopa dosing. Changes in cognition may be evident even in patients with early mild Parkinson s disease. With increasing age or increasing duration of Parkinson s disease, cognitive impairment may worsen further. The earliest changes seen include slowness of mental processing referred to as bradyphrenia, problems with working memory including storing and processing information, or reduction in executive functioning. This is often most apparent in patients who note difficulty in multi-tasking or doing more than one activity at once. Processing visiospatial information may also be affected relatively early in the disease and aberrant perception of distances associated with this can contribute to bradykinesia or reduced amplitude of movements.

5 Dementia is the greatest source of disability in advanced Parkinson s disease and unfortunately is the most common cause of nursing home placement. Overall, dementia affects about 40 percent of Parkinson s disease patients and risk increases with increasing duration of disease and increased age. The presence of dementia significantly increases mortality. After a duration of 15 years of Parkinson s disease, about 50 percent of patients may become demented and this increases to 80 percent after 20 years of Parkinson s disease. Hallucinations, poor response to levodopa, and increased severity of motor symptoms are associated with dementia. If dementia and parkinsonism occur within one year of each other, this is referred to as dementia with Lewy bodies. On the other hand, if parkinsonism precedes the development of cognitive impairment by several years, the dementia is referred to as Parkinson s disease dementia. For patients who develop dementia, we commonly simplify the anti-parkinson drug regimen, attempting to treat predominantly with levodopa. For its relative anti- Parkinson effect, levodopa is the best tolerated anti-parkinson medication and has less

6 tendency to produce drug-induced psychosis. Modifying the environment and sticking to a routine can be helpful behavioral treatment in dealing with some of the aberrant behaviors that can occur with Parkinson s disease. Rivastigmine has been approved for treatment of dementia associated with Parkinson s disease and another cholinesterase inhibitor, donepezil, has also been shown in smaller clinical trials to be helpful in modestly improving cognition in Parkinson s disease dementia. There is somewhat mixed data on the use of memantine suggesting that this medication might be helpful in some patients with Parkinson s disease dementia also. Treatment of associated behavioral problems such as anxiety, agitation, and hallucinations is also important since these behavioral symptoms may at times be more problematic for the caregiver and patient than cognitive impairment. Psychosis refers to the presence of hallucinations or delusions. Delusions means fixed abnormal thoughts and can often be manifest as paranoia which is an abnormal fear of others trying to do harm to oneself. Patients may also have delusions of infidelity or that others are trying to steal their belongings. Hallucinations in Parkinson s disease patients are typically visual hallucinations where the patient sees people, animals, or things that are unreal. Typically hallucinations may begin as a sense or presence where a patient may briefly see a person or thing in the periphery of vision and this disappears once the patient attends to that area around them. As hallucinations become more severe, the patient may see formed objects or people but retain insight that they are unreal. The hallucinations become quite troublesome when they are persistent and the patient loses insight that the people or things are unreal. Auditory hallucinations and other forms of hallucinations are uncommon in Parkinson s disease. Delusions and hallucinations are typically a manifestation of Parkinson s disease dementia and when they occur in patients who are not yet demented, they are a sign that cortical pathology is accumulating which will result in dementia in the near future. Anti-Parkinson medication worsens hallucinations and delusions. As a result, the medication regimen is typically simplified with levodopa used as a primary treatment and other secondary medications such as anti-cholinergics, amantadine, and then dopamine agonists reduce or dropped if possible. If hallucinations persist despite simplification of the medication regimen or the simplification of the medication regimen results in unacceptable worsening of motor symptoms, then antipsychotics are needed

7 in order to improve these symptoms. Generally, only the atypical antipsychotics quetiapine and clozapine are used since many of the other commonly used antipsychotics substantially worsen motor symptoms of Parkinson s disease.

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