MIAMI BEACH — Early and aggressive treatment of dementia in people with Parkinson's disease could optimize outcomes and quality of life for patients and their caregivers, growing evidence suggests.
Approximately one-third of people with Parkinson's disease experience dementia. “We know there is such high risk for dementia in this population. We need to be proactive,” Dr. David J. Burn said at the World Federation of Neurology World Congress on Parkinson's Disease and Related Disorders.
Hallucinations are a major concern. These can arise when mild cognitive impairment, common in people with Parkinson's disease, progresses to dementia.
“There is some reluctance to give the diagnosis. You have to be sure in your mind the dementia exists,” Dr. Burn said. “But giving this in a reasonable way might reassure people with hallucinations they are not going mad.” A definitive diagnosis can provide a sense of relief to patients and family members.
“Giving a positive diagnosis is still something that is not terribly well done,” said Dr. Burn, professor of movement disorder neurology at Newcastle (U.K.) University, Newcastle-Upon-Tyne.
Current patient age is the dominant risk factor for dementia in Parkinson's disease. Cognitive impairments (attention, executive functioning, visuospatial perception, and memory) and behavioral effects (apathy, mood) are clinical features often associated with this classic “dysexecutive visuoperceptual” dementia. “There is a high psychiatric burden in that dementia, which is important in management of the disease.”
General and specific diagnostic instruments can be helpful in this population, such as the Mini-Mental State Examination or the Mini-Mental Parkinson. Dr. Burn recommended the Neuropsychiatric Inventory-4. “It is a fairly quick thing to administer to the caregiver and can be administered with the Caregiver Distress Scale. It is quite a neat, compact way of assessing a lot quite quickly.”
“What we sometimes forget is why we are actually using them,” Dr. Burn said. “This is an important point. Never forget that just because the scale generates a number, we would never feel comfortable the number is robust. Always follow-up with an interview with the patient and the informant—that is essential.”
Fluctuation in symptoms is among the diagnostic challenges, Dr. Burn said. “They can have good hours/days versus bad hours/days—can have widely different values on neurologic testing. These fluctuations may be the biggest determinant of [impact on] activities of daily living in the setting of Parkinson's disease dementia.”
Other confounding factors can further complicate diagnosis, including an insidious onset, slow progression, motor effects of Parkinson's disease, and whether the impairment is the result of cognitive dysfunction, he said.
Multiple medications have been studied for efficacy in this comorbid population. These include clozapine (Clozaril), quetiapine (Seroquel), memantine (Namenda), rivastigmine (Exelon), and donepezil (Aricept). However, the level of evidence to support a particular agent varies in the literature, and many drugs have side effects that need to be considered. Cholinesterase inhibitors can have effects on the heart, including reports of hospital visits for syncope and bradycardia, for example.
“Most of us when we diagnose Parkinson's disease dementia would reach for a cholinesterase inhibitor if patients are symptomatic,” Dr. Burn said. “You need to push the dose to the maximum,” he advised.
Keep in mind patients do not always respond to the first agent, so a switch to a different agent in this class or a different type of medication may be warranted for some patients, he added.
Choice of agent is unclear in part because randomized, controlled trials of antipsychotics in Parkinson's disease frequently exclude demented cases, he said. Also, there is a lack of randomized, controlled trials to support use of quetiapine.
“The jury is out on memantine, but for the moment … studies are favoring use of the drug,” Dr. Burn said.
Dr. Burn and his colleagues are planning a study in which they will randomize 500 patients with Parkinson's disease and dementia to either donepezil or placebo. Secondary measures will include caregiver distress, strain, and health economics. “We hope to reconcile some unanswered questions.”
Disclosures: Dr. Burn disclosed that he was recently a member of the advisory board for Eisai Inc.
'We know there is such high risk for dementia in this population. We need to be proactive.'
Source DR. BURN