from Part three - Treatment issues
Published online by Cambridge University Press: 06 July 2010
Summary
Dementia occurs in PD and lesser cognitive deficits, of ‘frontal-lobe’ type, are detectable in nondemented patients even at diagnosis. Cortical Lewy bodies, Alzheimer changes and vascular disease have been considered to underlie clinical dementia in PD but, in nondemented cases, attention has been more focused on the neurochemical changes. Dopamine deficiency causes disruption to frontostriatal circuits but noradrenergic, cholinergic and serotonergic deficts also occur and are involved in cognitive and affective disturbance in other conditions.
Modulation of these transmitter systems in PD using drugs with specific neurochemical effects suggests that dopamine deficiency causes selective impairment in ‘frontal lobe’ functions, such as working memory and planning, but many functions are unaffected. Noradrenergic modulation also affects frontal-lobe function although both facilitatory and inhibitory effects occur. Cholinergic deficits render patients sensitive to the effects of anticholinergic therapy, particularly on memory. Serotonergic deficits are related to depression.
Our longitudinal studies show that a subgroup of patients dement early. Risk factors for dementia include greater age at diagnosis and rapidly progressive motor disability. CT scans at diagnosis show a high incidence of abnormality, suggesting that structural rather than neurochemical pathology is responsible for the cognitive deficits. Predictive factors for dementia can be established from the neuropsychological profile at diagnosis.
The pathology of cognitive impairment in PD is multifaceted. Neurochemical deficits are more amenable to therapy through standard pharmacological means but another challenge is to identify early risk factors for the development of cortical pathology so that neuroprotection can be developed and targeted at appropriate patients.
Cognitive impairment in Parkinson's disease
Although motor deficits are the most consistent signs of Parkinson's disease (PD), cognitive dysfunction also occurs.
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