Neuropsychiatric signs and symptoms in Parkinsons and treatment options
Join Prof Suzanne Timmons & Prof Iracema Leroi as they discuss: what are the most frequent Neuropsychiatric signs to look out for? When to refer to specialist services and what treatments are available?
Presentation slides - Prof Suzanne Timmons
Presentation slides - Prof Iracema Leroi
Signs and symptoms of Parkinson’s disease dementia
Cognitive impairment is common in early Parkinson’s, and 70% to 80% of people will experience it within eight years of diagnosis.
For between 25% and 50%, this will develop into Parkinson’s disease dementia (PDD) within 10 years.
Prof Suzanne Timmons, Consultant Geriatrician at the Mercy University Hospital and St Finbarr's Hospital, explained that this form of dementia was a Lewy body dementia, characterised by an abnormal build-up of alpha-synuclein proteins throughout the brain. The Lewy body pathology runs through six stages. It starts in the brainstem, causing constipation, mood and sleep disturbances, before spreading to the mid-brain, in stages three and four, resulting in motor symptoms. In stages five and six, it affects the cortex, leading to cognitive impairment and dementia. The biggest risk factor is advancing age, said Suzanne. Others include:
- More severe disease
- Prominent rigidity, rather than tremor
- Daytime sleepiness
- REM sleep disorder
- Low verbal fluency or executive function
- Apoe E genotype
“We should be measuring cognition in anyone with Parkinson’s. At my clinic, we routinely screen every one to two years. When we start to see a drop, we screen more often,” said Suzanne.
However, professionals must be careful, as bradyphrenia, or slow thought processes and responses related to off periods, is a core element of Parkinson’s. That means day-to-day fluctuations can sometimes be misinterpreted as improvements or declines.
“We should always make sure a person is in their optimum state… when we do cognitive testing, and we have to be really careful in interpreting tests that rely on motor function,” she added.
- Memory: reduced retrieval, but good recognition and responds to external cues
- Executive functioning: poor shifting in tasks, slowness in sequencing, poor insight
- Attention: reduced vigilance, fluctuates
- Speech: reduced verbal fluency
“When you put it all together, you see that a test like the Mini-Mental State Exam doesn’t really capture their problems,” said Suzanne. “Our test of choice is the Montreal cognitive assessment.”
Parkinson’s disease psychosis, which can involve hallucinations and delusions, can be a feature of PDD.
People with PDD often experience hallucinations. They are mainly visual, and tend to be complex and well formed. Some people experience “presence”, or a feeling that someone is in the room with them, or “passage”, a feeling that someone passed by.
There is a strong association between hallucinations and sleep disturbance, and they are not always distressing for the person. In addition, hallucinations are not always a symptom of dementia, Suzanne explained.
“It's really important that we don't confuse illusions for hallucinations, because a person with Parkinson's may have problems with processing visual information and can mistakenly think something like a coat is a person. Be cautious about hallucinations that are only happening in dim lighting and in the evenings,” she said.
“Similarly, I'm always sceptical of hallucinations that occur only in the middle of the night, because people with Parkinson's suffer from vivid dreams.”
Delusions occur in between 3% and 10% of cases, and they tend to be negative. Common delusions include:
- Phantom border syndrome, or believing someone is living in their home uninvited
- Othello syndrome, or delusions of infidelity
- Capgras syndrome, or believing an imposter has replaced a close friend or loved one
It is worth noting that delusions can sometimes be a side effect of dopamine agonists, said Suzanne.
Disinhibitory psychomotor behaviours can also be a sign of PDD. They include
- Impulse control disorders, such as pathological gambling, hypersexuality, compulsive shopping etc
- Punding, or excessive hobbyism, hoarding, excessive internet use etc
- Dopamine dysregulation syndrome, or excessive use of dopamine medications
Other common non-cognitive symptoms include:
- Depression and anxiety
- Apathy or impulsivity
- Agitation or restlessness
- Repetitive behaviours
Managing Lewy body dementias
Lewy body dementia is an umbrella term that covers PDD and dementia with Lewy bodies (DLB). Professor Iracema Leroi, Associate Professor of Geriatric Psychiatry at Trinity College Dublin, said:
“In many cases, it's very hard to tease them apart, so quite often, we think of the intervention and the treatment together.”
Treatment, she went on, should incorporate pharmacological and non-pharmacological approaches, and be delivered by a wrap around, multi-disciplinary team (MDT).
Setting the scene Iracema explained that there were no licensed treatments for PD-MCI, prodromal DLB, or DLB, and no disease modifying therapies for PD, PD-MCI, PDD, or DLB.
“The key thing is that if we intervene early, we can hopefully obviate the progression to full dementia syndrome,” she said.
Current treatments focus on symptom management, improving quality of life, reducing care burden, and reducing the risk of institutionalisation.
“Everything we do in terms of neuropsychiatric management in Parkinson's is compromise and negotiation between emption and motion”, said Iracema.
“Increasing dopaminergic load, particularly in more fragile, advanced, or older patients, will increase the risk of confusion, hallucinations, etc. It's always about trying to strike a balance. Of course, we can't remove the dopamine replacement entirely, but we need to try to optimise dose as much as possible,” she said.
Dual syndrome hypothesis
Iracema explained the the dual syndrome hypotheses, which argues there are two Parkinson’s “profiles”.
Profile 1, or “dementia sparing”, is characterised by fronto-striatal network dysfunction, modulated by the loss of dopaminergic and noradrenergic neurons. It affects attention and working memory, as well as executive function.
Profile 2, or “dementia prone”, is characterised by posterior cortical degeneration, modulated by acetylcholine loss. It causes memory, language, and visual/spatial symptoms.
“Thinking about the differences in neurotransmitters can inform the differences in interventions,” said Iracema.
Cholinesterase inhibitors, such as donepezil and rivastigmine can work very well in some people with PDD, said Iracema, adding that the more “neuropsychiatricaly complex” the patient, the better the response. She added that she recommends patches over capsules because of increased side effect tolerability. “I am then able to get to maximum dose in a greater proportion of people,” she said. In terms of preparation for treatment, she said teams should aim for levodopa monotherapy, and attempt a stepwise removal of “deliriogenic”, hallucinogenic medications, using a “last in, first out” methodology Memantine, is a N-methyl D-aspartate (NMDA) receptor antagonist licensed in Alzheimer’s is currently under investigation in PDD. Early results look promising, but more evidence is needed, said Iracema.
Iracema closed her talk by highlighting a number of cognition-based interventions for older adults. These included cognitive brain training, cognitive stimulation, and cognitive rehabilitation.
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De Michele, G., Palmieri, G. R., Pane, C., Dello Iacovo, C. D. P., Perillo, S., Saccà, F., ... & De Rosa, A. (2021). Othello syndrome in Parkinson’s disease: a systematic review and report of a case series. Neurological Sciences, 42(7), 2721-2729.
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This webinar has received sponsorship from Zambon UK Ltd. The first session in the webinar is designed and delivered by the Parkinson's Academy and sponsored by Zambon UK Ltd; the sponsor has had no input into the educational content or organisation of the session.
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