Article

Cognitive dysfunction and dementia in Parkinson's disease

Department of Neurology, Research Institute Neurosciences Vrije Universiteit, VU University Medical Center, Amsterdam, The Netherlands.
Journal of Neural Transmission (Impact Factor: 2.87). 11/2004; 111(10-11):1303-15. DOI: 10.1007/s00702-004-0168-1
Source: PubMed

ABSTRACT 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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    • "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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    • "Central cholinergic disturbances are present in many neuropsychiatric and neurodegenerative diseases. In various forms of dementia, such as Alzheimer's dementia (AD) or Lewy body dementia, cholinergic deficits in the brain [1] [2] are associated with cognitive decline [3] [4] [5] and are thought to precede clinical symptoms. "
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    06/2011; 2011:709416. DOI:10.1155/2011/709416
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    • "There is evidence that already a slight deterioration of cognition may enhance the risk of conversion to dementia in PD [4] [5]. However, not all PD patients with such a cognitive profile develop dementia (PDD), and early identification of these patients with particularly increased risk is still not possible with sufficient accuracy [5] [6] [7]. Therefore, a lot of effort has been put on the identification of a clinical risk profile and especially in the characterization of mild cognitive deficits in patients who are later on developed dementia [8]. "
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    05/2011; 2011:540843. DOI:10.4061/2011/540843
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