What causes mental dysfunction in Parkinson's disease?

Abstract

Abstract:Parkinson's disease (PD) is frequently associated with mental dysfunction. Domain-specific cognitive deficits are ubiquitous, and although they may not be clinically apparent in all patients, they are demonstrable by neuropsychological testing. Dementia is less frequent but is present significantly more in PD patients than in controls, with a cumulative prevalence rate up to 40% and up to six-fold increased incidence. Cognitive impairment mainly involves executive and visuospatial functions; memory is secondarily impaired with relatively preserved recognition. Qualitatively, the neuropsychological profile of dementia encompasses the same type of deficits found in nondemented PD patients. The dementia seen in PD, therefore, can be described as a dysexecutive syndrome combined with visuospatial dysfunction and behavioural symptoms. Dopaminergic, noradrenergic, serotoninergic, and cholinergic deficits have all been described as the underlying neurochemical impairment, but the strongest evidence exists for a cholinergic dysfunction. Involvement of brainstem nuclei, limbic structures, and cerebral cortex have been suggested as the site, and Lewy body (LB) degeneration and Alzheimer-type changes as the type of pathology underlying the mental dysfunction in PD. Although there is still some controversy as to the site and type of pathology, recent evidence suggests that LB-type degeneration in limbic structures and cerebral cortex, with consequent synaptic and cell loss, is the main pathological state associated with dementia in PD.

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

“…The risk of dementia significantly increases with age. Cholinergic deficits and cortical Lewy bodies have been associated with the occurrence of PD dementia (PDD), while cognitive impairments are most likely due to the early and progressive degeneration of monoaminergic systems to associative cortical and subcortical regions (Rinne et al, 2000;Emre, 2003). Acetylcholinesterase inhibitors are first-line therapy in patients with PDD.…”

Dementia Associated with Parkinsons Disease

“…There have been a number of clinical-pathological correlation studies supporting one or the other view. 7 Since the beginning of 2000, several carefully performed studies have become available that used alphasynuclein antibodies to identify LB pathology (which is more sensitive than the traditional ubiquitin staining), and assessed LB-and AD-type pathologies in parallel. The results of these studies suggest that dementia in PD best correlates with LB pathology in limbic and cortical areas.…”

Metabolic brain networks associated with cognitive function in Parkinson's disease

“…The direct dopaminergic connections between the ventral tegmental area and the prefrontal cortex may also influence changes in cognition in this disease (e.g., Mattay et al, 2002;cf., Cools, 2006 for review). Nonetheless, the modulation of dopamine systems cannot fully explain the cognitive deficits in PD, and other neurotransmitter systems may be influential (Emre, 2003;Pillon et al, 2003;Bosboom et al, 2004). Moreover, recent postmortem studies in PD suggest a correlation between dementia and cortical Lewy body formation as well as coincident Alzheimer's disease-associated neurofibrillary pathology (Braak et al, 2003(Braak et al, , 2005Kovari et al, 2003).…”