Cognitive dysfunction and dementia in Parkinson's disease

VU University Amsterdam, Amsterdamo, North Holland, Netherlands
Journal of Neural Transmission (Impact Factor: 2.4). 11/2004; 111(10-11):1303-15. DOI: 10.1007/s00702-004-0168-1
Source: PubMed


Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder mainly characterized by degeneration of dopaminergic neurons in the substantia nigra and the ventral tegmental area, in combination with a varying loss of central noradrenergic (locus coeruleus), cholinergic (nucleus basalis of Meynert) and serotonergic (dorsal raphe nuclei) integrity, leading to a multitude of motor and non-motor behavioral disturbances.
Apart from the clinical motor hallmarks, in the early stages of disease, subtle cognitive dysfunction might be seen comprising mainly executive dysfunction, with secondary visuospatial and mnemonic disturbances. In about 20–40% of patients, these problems may eventually proceed to dementia, which constitutes an important risk factor for caregiver distress, decreased quality of life and nursing home placement. Dementia in PD is typically characterized by a progressive dysexecutive syndrome with attentional deficits and fluctuating cognition, often accompanied by psychotic symptoms. It is thought to be the result of a combination of both subcortical and cortical changes. PD-related dopaminergic deficiency in the nucleus caudatus and mesocortical areas (due to degeneration of projections from the substantia nigra and ventral tegmental area) and cholinergic deficiency in the cortex (due to degeneration of ascending projections from the nucleus basalis of Meynert), combined with additional Alzheimer-pathology and cortical Lewy bodies, may greatly contribute to dementia.
Current treatment of dementia in PD is based on compensation of the profound cholinergic deficiency. Recent studies with the cholinesterase inhibitors galantamine, donepezil and rivastigmine show promising results in improving cognition and ameliorating psychotic symptoms, which must further be confirmed in randomized controlled trials.

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Available from: Erik Ch. Wolters
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    • "The mesolimbic pathway is mainly associated with reward, while the mesocortical pathway is associated with cognitive function. Aberrant reward processing drives substance abuse disorders, and cognitive dysfunction exists as an often overlooked but devastating feature of many neuropsychiatric disorders (Carter et al., 1998; Bosboom et al., 2004; Medalia and Lim, 2004). Studies of imbalanced mesolimbic and mesocortical DAergic signaling support a potential therapeutic role for DA in reward and cognitive dysfunction in neuropsychiatric disease (Murphy et al., 1996; Volkow et al., 1998; Goldman-Rakic et al., 2004). "
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    • "However, the clinical expression of the disease is more heterogeneous as patients suffer from a variety of additional non-motor symptoms, including sleep disturbances, olfactory deficits, cognitive impairment, neuropsychiatric disorders, and autonomic dysfunction [4], [5]. In particular, the cognitive deficit seen in PD causes disturbances in both executive functions and memory [6] and may lead to dementia in 30 to 40% of the patients as the disease progresses [7], [8]. "
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    • "In contrast, MPTP-infused rats displayed a poor performance in the shortterm retention session (1.5 h after training) of the inhibitory avoidance task (Castro et al., 2012), in the working memory version of the water maze (Prediger et al., 2006) and in the social recognition task (Moreira et al., 2010; Castro et al., 2012). These findings are consistent with the view of human studies suggesting that PD patients present early deficits in working memory and short-term memory tasks mainly dependent on the frontostriatal circuitry (for review see Zgaljardic et al., 2003) with long-term spatial (declarative) memories mostly spared (Dubois and Pillon, 1997; Bosboom et al., 2004). Beyond the cognitive symptoms, depressive disorders commonly occur in PD affecting approximately 40% of the patients during the early stages of the disease (Tolosa et al., 2007). "
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