MIAMI BEACH—While motor impairments are hallmark features of Parkinson’s disease, there is growing appreciation that the nonmotor features of the disease, including dementia, proceed in step with motor disability and may be equally debilitating. “The cause of dementia in Parkinson’s disease is multifactorial—much more so than in Alzheimer’s disease,” commented Hubert H. Fernandez, MD. Among patients with Parkinson’s disease and dementia, many cases will be due to concomitant Alzheimer’s disease, while others are due to true Parkinson’s disease– related dementia. Vascular dementia is also prevalent in patients with Parkinson’s disease. Dr. Fernandez is Director of Clinical Trials at the University of Florida–Gainesville’s Movement Disorders Center.

A DISEASE OF THE BODY AND THE MIND

Parkinson’s disease–related dementia is somewhat distinct from other etiologies, remarked Dr. Fernandez at the 57th Annual Meeting of the American Academy of Neurology. “There is not as much memory loss and not as much difficulty storing new memories, but there is significant difficulty with retrieval of information.” Patients are slower to respond, but with prompting and cuing they can usually remember.

Less is known, however, about the timing of cognitive impairment in the disease. “We are able to track motor impairment very well,” he said, because it is easy to observe in the clinic. “But we only appreciate the cognitive impairment when it is severe enough to have an effect on function.” Nonetheless, his hunch was that mild cognitive impairment occurs early on in the disease. “We might consider a little bit of forgetfulness as similar to a tremor in the pinky,” he said. “Our hypothesis was that patients are equally affected by motor and cognitive impairment” and that the two develop together.

To test this hypothesis, he retrospectively examined the charts of 72 randomly selected patients with Parkinson’s disease who had been evaluated using both the United Parkinson’s Disease Rating Scale for motor impairment and standard neuropsychological testing. The latter was a routine part of patient care, he stressed, and was administered to all patients regardless of cognitive status.

What he found was that patients with mild motor problems also had mild cognitive problems, and that worsening motor scores predicted worsening cognitive scores. Surprisingly, neither age, gender, nor disease duration was a significant predictor of cognitive decline. For example, a patient with mild parkinsonism for 20 years was not likely to have dementia, while a patient who progressed rapidly over five years was.

Subitem analysis on the motor scale suggested that axial signs were more predictive than appendicular signs. Patients with right-sided impairment and bradykinesia were more likely to have dementia than those with left-sided impairment and tremor, Dr. Fernandez reported.

TREATING THE BODY

The presence of dementia makes it more difficult to treat the motor aspects of the disease. “Dementia is the most limiting factor for pharmacological management of patients with Parkinson’s disease,” remarked Dr. Fernandez. When a patient has dementia, increasing drugs that treat the motor symptoms of the disease will often worsen cognition and may exacerbate psychotic symptoms as well. Dementia is a “relative contraindication” for dopamine agonists. “We become very conservative in pharmacologic motor management when a patient is demented,” he said.

TREATING THE MIND

“The reason our study is important is that you can treat these patients,” commented Dr. Fernandez. The same medications that are used for Alzheimer’s dementia—including donepezil and rivastigmine—work for Parkinson’s dementia. “They work just as well, if not better, than in Alzheimer’s disease,” he said. This makes sense in terms of pathology, he noted, since it is clear that Parkinson’s disease causes a cholinergic deficit, along with its more widely recognized effects on dopamine neurons. “The cholinergic deficit in parkinsonian brains is as much—if not more—as that in Alzheimer’s brains,” he said.

Dr. Fernandez observed that sometimes neurologists are leery of prescribing cholinesterase inhibitors, because of concerns about worsening tremor. Double-blind studies have shown, however, that this is not a major concern in most patients. “If a patient is unable to tolerate them,” he said, “it’s possible to use memantine,” which is also a cognitive enhancer and has no cholinesterase-inhibiting effects. It is also a chemical cousin of amantadine, which improves dyskinesias, “so you might actually shoot two birds with one stone.”

The choice of when to begin therapy “depends on your definition of when cognitive dysfunction occurs,” said Dr. Fernandez. “Our standard might be too late for the majority of patients. A study like ours points to starting treatment earlier on.”

NR

—Richard Robinson

Suggested Reading
Cahn-Weiner DA, Grace J, Ott BR, et al. Cognitive and behavioral features discriminate between Alzheimer’s and Parkinson’s disease. Neuropsychiatry Neuropsychol Behav Neurol. 2002;15:79-87.
Ravina B, Putt M, Siderowf A, et al. Donepezil for dementia in Parkinson’s disease: a randomised, double blind, placebo controlled, crossover study. J Neurol Neurosurg Psychiatry. 2005;76:934-999.

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