Neurocognitive Psychiatric and Neuropsychological Alterations in Parkinson’s Disease: A Basic and Clinical Approach (original) (raw)
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Parkinson’s disease (PD) is associated with a large burden of non-motor symptoms including olfactory and autonomic dysfunction, as well as neuropsychiatric (depression, anxiety, apathy) and cognitive disorders (executive dysfunctions, memory and learning impairments). Some of these non-motor symptoms may precede the onset of motor symptoms by several years, and they significantly worsen during the course of the disease. The lack of systematic improvement of these non-motor features by dopamine replacement therapy underlines their multifactorial origin, with an involvement of monoaminergic and cholinergic systems, as well as alpha-synuclein pathology in frontal and limbic cortical circuits. Here we describe mood and neuropsychiatric disorders in PD and review their occurrence in rodent models of PD. Altogether, toxin-based rodent models of PD indicate a significant but non-exclusive contribution of mesencephalic dopaminergic loss in anxiety, apathy, and depressive-like behaviors, as ...
Parkinson's Disease, 2011
Cognitive abnormalities are a feature of Parkinson's disease (PD). Unlike motor symptoms that are clearly improved by dopaminergic therapy, the effect of dopamine replacement on cognition seems paradoxical. Some cognitive functions are improved whereas others are unaltered or even hindered. Our aim was to understand the effect of dopamine replacement therapy on various aspects of cognition. Whereas dorsal striatum receives dopamine input from the substantia nigra (SN), ventral striatum is innervated by dopamine-producing cells in the ventral tegmental area (VTA). In PD, degeneration of SN is substantially greater than cell loss in VTA and hence dopamine-deficiency is significantly greater in dorsal compared to ventral striatum. We suggest that dopamine supplementation improves functions mediated by dorsal striatum and impairs, or heightens to a pathological degree, operations ascribed to ventral striatum. We consider the extant literature in light of this principle. We also surv...
Journal of Neural Transmission, 2004
The cognitive and behavioral sequelae (i.e., nonmotor profile) of Parkinson's disease (PD), with executive dysfunction and depression being most prominent, have typically been overshadowed due to an emphasis on motor symptomatology. The apparent categorization of PD as a disorder isolated to the dopaminergic system may be a generalization of the disease pathology. Dopamine therapy, used for the treatment of motor symptoms, has not consistently been shown to resolve nonmotor impairments. Research evidence indicates that nondopaminergic neurotransmitter systems (i.e., serotonergic, noradrenergic, & cholinergic) are disrupted in PD and may contribute to cognitive and behavioral dysfunction. Furthermore, Lewy bodies within cortical and subcortical structures can add to the nonmotor profile in PD. Pharmacological interventions for the treatment of cognitive and behavioral impairments associated with PD are few, especially for nondemented patients. The current review of the literature highlights evidence that associates nonmotor dysfunctions with neurochemical and clinicopathological correlates of PD.
The neurobiological basis of cognitive impairment in Parkinson's disease
Movement Disorders, 2014
The recent formalization of clinical criteria for PD with dementia (PD-D) codifies many studies on this topic, including those assessing biological correlates. These studies show that the emergence of PD-D occurs on the background of severe dopamine deficits with the main pathological drivers of cognitive decline being a synergistic effect between α-synuclein and Alzheimer's disease pathology. The presence of these pathologies correlates with a marked loss of limbic and cortically projecting dopamine, noradrenaline, serotonin and acetylcholine neurons, although the exact timing of these relationships remains to be determined. Genetic factors, such as triplications in the α-synuclein gene, lead to a clear increased risk of PD-D, while others, such as parkin mutations, are associated with a reduced risk of PD-D. The very recent formalization of clinical criteria for PD with mild cognitive impairment (PD-MCI) allows only speculation on its biological and genetic bases. Critical assessment of animal models shows that chronic low dose MPTP treatment in primates recapitulates PD-MCI over time, enhancing the current biological concept of PD-MCI as having enhanced dopamine deficiency in frontostriatal pathways as well as involvement of other neurotransmitter systems. Data from other animal models support multiple transmitter involvement in cognitive impairment in PD. While dopamine dysfunction has been highlighted because of its obvious role in PD, the role of the other neurotransmitter systems, neurodegenerative pathologies and genetic factors in PD-MCI remain to be fully elucidated.
Neuropsychiatry of Parkinson's Disease: A Current Overview
Parkinson's disease (PD) may be accompanied by various non-motor symptoms ranging from neuropsychiatric symptoms to autonomic and sensory dysfunctions and sleep disorders, including depression, anxiety, sleep disturbances, psychosis, and behavioural and cognitive changes. Currently, research on PD has ceased to focus exclusively on its motor symptoms, broadening the focus to aspects that are usually affected in the course of the disease and that are very limiting for the patient, such as they are the cognitive, behavioural and functional aspects. The neurobiological bases for the development of neuropsychiatric disorders in PD are increasingly known. For patients and families, these neuropsychiatric conflicts are often more problematic and distressing than the motor aspects of PD. This symptoms often precede typical motor symptoms with consequent importance for early diagnosis and treatment.
A comprehensive overview of the neuropsychiatry of Parkinson's disease: A review
Bulletin of the Menninger Clinic, 2017
Parkinson's disease is a widespread neurological illness. However, its psychiatric links have also been discussed lately by many authors, which has brought more depth to the specialized field of neuropsychiatry. Neuropsychiatric complications are commonly seen in Parkinson's patients, including major depression, anxiety, psychosis and hallucination, and cognitive abnormality. Almost all of these complications have a distinct pathophysiology and treatment. In this article we review the most recent studies about the association of these symptoms with Parkinson's disease and highlight the epidemiology, diagnosis, pathophysiology, and treatment of the neuropsychiatric complications, with more emphasis on the pathophysiology of these complications.
Neurodegeneration and cognition in Parkinson' s disease: a review
neurodegenerative disorder of the dopaminergic neurons in the substantia nigra. Much of the scientific literature on the Parkinson's disease has been focused on the evaluation and management of motor conditions in PD. Much less stress has been laid on evaluating and managing the cognitive disturbances found comorbidly in this condition. Studies have suggested that the cognitive dysfunction observed in PD can range anywhere from individual cognitive deficits to the clinical picture of minimal cognitive impairment to as much as a full-blown dementia like clinical picture. Perhaps because of this poor understanding, the treatments for this comorbidity have not been able to be adequately developed. Right now, only rivastigmine is the approved drug of choice for treatment of dementia associated with PD. In this review we aim at elaborating the individual cognitive deficits associated with PD instead of focusing on full-blown dementia. Our aim at focusing on individual symptoms is important because these symptoms should be evaluated even at the most beginning stages of PD rather than waiting for the patient to report for the symptoms. Therefore, we will aim at elaborating the prevalence, symptomatology and implications for treatment for these cognitive dysfunctions individually. Because covering all the domains of cognitive dysfunctions are not possible here, we will focus on three cognitive impairments which are most commonly observed in the PD patients. These are the (1) Executive function deficits (2) Memory deficits and (3) visuospatial deficits. We will, finally, have an overview of the condition of minimal cognitive deficits observed in PD.
A Rat Model of the Cognitive Impairments in Parkinson's Disease
Revista mexicana de …, 2006
Although Parkinson's disease (PD) is classically considered to be a motor system disease, subtle cognitive impairments can be observed even during the early phases of PD. In this article we review behavioral and neurochemical studies on the cognitive alterations observed in rats treated with intranigral infusion of the neurotoxin MPTP. The critical role of dopamine release in the dorsal striatum and its modulation by adenosine receptors is also reviewed as a potential strategy to treat the cognitive disabilities of PD patients who do not improve with levodopa therapy. Most of the impairments presented by rats treated with intranigral infusion of MPTP are similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons (40-70%) results in sensory and memory defi cits with no major motor impair-*