The Hallmark Of Parkinson

The hallmark of Parkinson's disease is involvement of the motor system, causing tremor, rigidity, and slowness of movement. But cognitive symptoms are frequently present at the time of diagnosis, contribute heavily to disability, and progress to dementia at an alarming rate. Dementia will develop in 40 to 70 percent of patients with Parkinson's disease during the course of their illness.

Theterm "Parkinson's disease dementia" refers to dementia that develops at least two years after the diagnosis of Parkinson's disease. If dementia develops before or within two years after the onset of motor symptoms, then the criteria are met for the related condition, diffuse Lewy-body disease. Risk factors for Parkinson's disease dementia include advanced age, treatment-induced visualhallucinations, and more severe motor symptoms. The cognitive profile is similar to that of Alzheimer's disease, but patients with Parkinson's disease dementia generally have more severe visuospatial deficits, large fluctuations in attention, frequent visual hallucinations, and less severe memory problems.

Parkinson's disease dementia and diffuse Lewy-body disease share a common neuropathological pattern,cognitive profile, and clinical course. The two conditions lie on the same disease spectrum, with the system that is initially involved -- motor in Parkinson's disease dementia and cognitive in diffuse Lewy-body disease -- artificially splitting them. Both can be considered subtypes of the more inclusive diagnosis of dementia with Lewy bodies. This larger category probably accounts for 10 to 15percent of cases of dementia, making it the second most common cause of dementia after Alzheimer's disease. The pathological hallmark of both Parkinson's disease dementia and diffuse Lewy-body disease is the presence of Lewy bodies -- intracytoplasmic neuronal inclusions containing alpha-synuclein -- in neocortical and paralimbic regions. By contrast, Lewy bodies are generally restricted tosubcortical structures such as the substantia nigra in patients who have Parkinson's disease without dementia. The majority of patients who have dementia with Lewy bodies also have pathological findings characteristic of Alzheimer's disease, which adds to the nosologic challenge.

The care of patients who have dementia with Lewy bodies is extremely challenging. Dopaminergic agents frequently worsenhallucinations and cognitive symptoms, whereas the older antipsychotic agents, or typical neuroleptics, can precipitate a profound, even fatal worsening in the motor symptoms of patients with parkinsonism. In general, the goal of therapy is to achieve acceptable motor function with the use of the lowest dose of levodopa and to control troubling hallucinations by adding low doses of atypicalneuroleptics such as olanzapine, quetiapine, or clozapine. Evidence from a number of lines of study suggests that increasing cholinergic function can be particularly beneficial for both cognitive and behavioral symptoms in patients with Parkinson's disease dementia, since it has already been found to be effective for these symptoms in a smaller study of patients with diffuse Lewy-body disease. Patientswith Parkinson's disease dementia have a greater cholinergic deficit than those with Alzheimer's disease, and the extent of the deficit correlates with the severity of cognitive symptoms; patients with Parkinson's disease dementia also have less devastation in the number of neocortical neurons, which can benefit from cholinergic repletion.

References (abridged):

1. Foltynie T, Brayne CE,Robbins TW, Barker RA. The cognitive ability of an incident cohort of Parkinson's patients in the UK: the CamPaIGN study. Brain 2004;127:550-560

2. Weintraub D, Moberg PJ, Duda JE, Katz IR, Stern MB. Effect of psychiatric and other nonmotor symptoms on disability in Parkinson's disease. J Am Geriatr Soc 2004;52:784-788

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