In mid-June, the Parkinson and Movement Disorder (PMD) Alliance offered a webinar on cognition and psychosis in Parkinson’s disease (PD), featuring geriatric psychiatrist Daniel Weintraub. He provided an overview of the neuropsychiatric and cognitive symptoms that can occur in PD, as well as how they are managed. Additionally, there was a question and answer session. We at Stanford Parkinson’s Community Outreach viewed the webinar and are sharing our notes.
This webinar was recorded and can be viewed here.
For additional resources on cognition – including downloadable guides, links to online resources, and webinars and podcasts – see these pages on the Stanford Parkinson’s Community Outreach website:
Now… on to our notes from the webinar.
Cognition and Psychosis – Webinar notes
Presented by the Parkinson and Movement Disorder Alliance
June 17, 2020
Summary by Lauren Stroshane, Stanford Parkinson’s Community Outreach
Dr. Daniel Weintraub is a geriatric psychiatrist. He discussed the range of symptoms that comprise PD psychosis, including illusions, hallucinations, and delusions. He also covered the changes in memory and thinking that can occur in PD. For each topic, he described how these symptoms may present, potential risk factors, how the symptoms are assessed, and management options.
For a person with Parkinson’s disease (PD) and their care partner, the non-motor symptoms of PD may eventually impact quality of life more than motor symptoms like tremor and slowness. Cognitive changes and psychosis are difficult topics to talk about, but knowing what they entail can allow you to better participate in your care and have more agency if they do occur. Many people with PD have no psychiatric or cognitive complications, but it is best to be aware of these possible symptoms.
The speaker mentioned that depression and anxiety are also important changes that happen for many with PD, however, he did not have time to cover them in this presentation.
Resources for those with depression can be found here.
Resources for those with anxiety can be found here.
Some important caveats
Dr. Weintraub wanted to be clear that, in general, those with PD cope extremely well despite their chronic and progressive neurologic disease. Many experience no cognitive or psychiatric complications, and when they do, it is not the fault of the patient or a sign of weakness.
Additionally, he believes that PD and its treatments may have under-recognized positive effects. For instance, some of the medications commonly used to treat PD – dopamine agonists such as Mirapex or Requip, and monoamine oxidase inhibitors such as rasagiline or selegiline – can sometimes trigger benefits in mood or cognition. Dopamine agonists sometimes enhance creativity. As we gain a better understanding of life and relationships, we see that sometimes there can be positive consequences to an otherwise upsetting diagnosis such as PD: personal growth and greater marital quality sometimes result.
What is psychosis?
To a psychiatrist, psychosis means hallucinations, delusions, or both.
Hallucinations are sensory perceptions that don’t actually exist as real stimuli; they are usually visual, but may also be auditory, olfactory, or tactile. Illusions are a milder phenomenon, the misidentification of an actual stimulus, such as seeing a sweater on a bed and mistaking it for a cat. Both hallucinations and illusions occur when the person is fully awake; they are not the same as vivid dreams.
Earlier in the illness, mild changes can lead to passage phenomena, the sense of something moving in the periphery of your vision, and presence phenomena, the sense of another person being in the room with you.
Delusions are fixed, false beliefs not based in reality; the occur more often in those with severe cognitive impairment, and often present as paranoia (also called persecutory ideation) – believing there are intruders in the house, or that a spouse has been unfaithful. Delusions usually occur after there have already been hallucinations.
What causes psychosis in PD?
The causes of psychosis are complex and often multi-factorial; it is likely a complicated interaction involving three key brain chemicals: dopamine, serotonin, and acetylcholine.
Other factors often associated with psychosis:
- PD medications
- Increasing severity of PD
- Cognitive impairment
- Increasing age
- Visual impairment
- Co-morbid psychiatric disorders, including REM sleep behavior disorder
Clinical management: PD medications
Sometimes it is necessary to decrease or stop some of the medications that were being used to treat PD symptoms, in case they are triggering or exacerbating psychosis.
There is an established order in which to discontinue PD medications if psychosis is a concern, starting with those most likely to be causing psychotic symptoms, from those less likely to cause these symptoms:
- Anticholinergics — most likely
- Dopamine agonists (Mirapex, Requip, Neupro)
- MAO-B inhibitors (Azilect, selegiline)
- Levodopa (Sinemet, Rytary) — least likely
It is also very important to rule out any underlying health issue that could be causing an acute change in cognition, such as a urinary tract infection (UTI), electrolyte imbalance, or pneumonia.
If symptoms are impacting the quality of life and safety of care, it may be necessary to add antipsychotic medication. Treating psychosis is a balancing act between addressing psychotic symptoms while trying not to worsen PD motor symptoms.
The “typical” antipsychotic medications (such as Haldol and Thorazine, among others) should no longer be used in PD, as they block dopamine receptors in the brain and can severely worsen PD symptoms.
The “atypical” antipsychotics can be used more safely in those with PD. Risperdal, Zyprexa, and Abilify are some examples from this category. Quetiapine (Seroquel) has generally been the first line antipsychotic to try for those with PD-associated psychosis, though clinical trials have been inconclusive. Clozapine seems to work at low doses as well and has clear evidence, however, it requires weekly blood monitoring for the first 6 months, to ensure white blood cell count doesn’t drop.
More recently, pimavanserin (Nuplazid) was FDA-approved specifically to treat hallucinations and delusions associated with Parkinson’s disease psychosis. It affects the serotonin system in the brain but not dopamine, so carries less likelihood of worsening motor symptoms. There was media attention about concerns for possible elevated death risk on this medication, but there is no actual scientific evidence of increased death risk in PD patients taking this drug.
There is, however, some evidence that other antipsychotic medications carry a slightly higher risk of death for patients with dementia who are taking them. This is not specific to any one drug, but rather the whole drug class. The risk is small, but worth taking into consideration when deciding whether to start one of these medications.
What cognitive changes occur in PD?
The terminology used for cognitive impairment is all borrowed from Alzheimer’s disease (AD); it is not specific to PD.
The first category is mild cognitive impairment (MCI), where the individual may report some cognitive decline and shows some impairment on neuropsychological testing, but they are able to function normally in their day-to-day life.
Dementia is the second category, where greater impairment is seen on neuropsychological testing across multiple cognitive domains, and they are experiencing significant changes in their ability to function normally.
Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are related diseases. In DLB, the dementia typically precedes motor symptoms, whereas in PDD, motor symptoms are present before dementia occurs.
Typically, those who had have a clear PD diagnosis for a period of time are not also diagnosed with Alzheimer’s disease. However, we have seen in the brains of deceased patients that sometimes those with PD pathology can have mixed AD pathology present as well, particularly in elderly individuals.
What are the risk factors for cognitive changes?
- Increasing age
- Advanced progression of PD
- Male sex
- Less formal education
- “Atypical” PD features, such as tending to have akinetic-rigid motor symptoms or postural instability early in the disease, rather than tremor
- Deep brain stimulation (DBS) is associated with mild decline in some patients, particularly with word-finding and memory
- This is why DBS candidates undergo rigorous neuropsychological testing before undergoing surgery, to assess the risks
- It’s unclear whether it is due to the surgery, to the stimulation, or both
What aspects of cognition are affected?
There are 5 main cognitive domains that are potentially impacted in PD:
- Executive function – Tasks that require planning, sequencing events, adapting, problem solving, and complex concepts
- Attention – Reaction times, awareness, and consistency
- Visuospatial function – The understanding of and relationship to objects in space
- Memory (retrieval vs. encoding) – Unlike in AD, in PD, the difficulty with memory is that it can be harder or slower to retrieve memories, but they are usually not lost entirely.
- Language skills –Word-finding problems are often reported, especially later in the disease.
One class of drugs used to treat cognitive decline is cholinesterase inhibitors. One of these medications is specifically approved by the FDA to treat PD dementia: rivastigmine (Exelon). In clinical trials, 20 percent of subjects had meaningful improvement, so it is not useful for everyone. Rivastigmine is usually well tolerated, though it can cause nausea and vomiting or worsen tremor.
Studies of another drug, memantine (Namenda), have been mixed, but it is often tried for those with PD as it seems to help some individuals with attention and memory.
What else can I do?
Someday, we hope to have treatments that actually slow or reverse progression of PD; we would expect this to help the cognitive symptoms of PD as well as the motor symptoms. For now, there are lifestyle changes you can make to maximize your cognitive abilities where they are at currently:
- Cardiovascular exercise
- Maintain a healthy weight
- Minimize vascular risk factors
- Cognitive “exercise” such as crossword puzzles, trivia games, or electronic brain teasers
- Limit medications that can worsen thinking, such as anticholinergic, benzodiazepine, and opiate medications
- Treat any psychiatric symptoms that are present, such as depression or anxiety
- Get good sleep and treat any sleep disruptions like obstructive sleep apnea or REM sleep behavior disorder
- Treat orthostatic hypotension, if it is present
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Question & Answer Session
Q: Is there a benefit for screening for cognition and psychosis in those with PD just because they have the diagnosis, or do you usually wait for symptoms to be brought up?
A: Yes, though not because we have good treatments – we don’t. Rather, it can be more informative for patients to understand that this can be part of PD. Annual screening for thinking abilities and routine monitoring of mood, anxiety, hallucinations, etc. is a good idea. It will also help to determine what PD treatments are most appropriate. Often, these symptoms start very gradually and worsen over time, so it can be difficult to perceive them early on.
Q: What tests would you do if someone comes to an appointment complaining of new onset of cognitive difficulties or hallucinations?
A: Check vital signs and perform a urinalysis to make sure there is no urinary infection and that the vitals are okay – both infection and low blood pressure can cause cognitive side effects! A complete blood count will also indicate if there is infection. A blood chemistry panel can rule out electrolyte imbalances that can also impact mental status. Psychiatrists often check thyroid levels, vitamin B12, and folate as well. Vitamin D is sometimes checked too, but in the speaker’s experience, it is always low, so it’s unclear whether that is triggering an acute change in cognition.
Syphilis is rare in our population but is sometimes tested. Imaging is usually not that useful; a CT scan, for instance, is usually looking for a stroke.
Q: Do you recommend any nutritional supplements for those concerned about their cognitive abilities?
A: Dr. Weintraub tends to wait until there is a clear scientific consensus before recommending things to his patients; he just does not feel our knowledge is there yet. At the same time, he does not feel there is any likely harm to trying supplements for this purpose.
Q: At what point should someone undergo formal neuropsychological testing? What does it entail?
A: Screening at a typical follow-up visit with your neurologist would most likely be in the form of the Montreal Cognitive Assessment (MoCA) and typically takes about 10-15 minutes. It’s a quick assessment of all the major domains of cognitive function.
When we say formal neuropsychological testing, we mean a battery of different cognitive tests that will evaluate many aspects of cognitive function, giving you the most detailed information about your mental abilities compared to other people in the population.
Now, with the pandemic, we have to think about whether these tests can effectively be done remotely, since for the time being we cannot usually see people in person for this testing. Researchers are trying to develop similar tests that one could complete on one’s own by computer.
Q: Can you mention again what medications I should avoid if I am concerned about my mental abilities?
A: You can refer to the Beers List from the American Geriatric Society, which is a very detailed list outlining which medications carry concerns for older adults and what the level of evidence is to support this. It is available as a PDF here: https://dcri.org/beers-criteria-medication-list/
You can use this list to look up any medications you’re on, and see if there are possible side effects that would be worrisome for you.
Broadly, anticholinergic medications, opiates, and benzodiazepines (often prescribed for anxiety) are not recommended. Dopamine agonists, sometimes used to treat PD motor symptoms, can impact cognition, particularly in older adults.
Q: What are your thoughts on using marijuana or CBD in the context of cognition in PD?
A: These are not substances he recommends for his patients; there is very limited evidence so far. Anecdotally, for those with severe anxiety or sleep issues, it may possibly be helpful. Preparations of marijuana that include the chemical THC – which cases users to get “high” – might potentially worsen psychosis, if present. He thinks there will likely be many studies on this in the coming years.