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Aldehyde dehydrogenase 2 is associated with cognitive functions in patients with Parkinson's disease.

ABSTRACT: Neurotransmitter degradation has been proposed to cause the accumulation of neurotoxic metabolites. The metabolism of these metabolites involves aldehyde dehydrogenase 2 (ALDH2). The Asian-specific single nucleotide polymorphism rs671 causes reduced enzyme activity. This study aims to explore whether Parkinson's disease (PD) patients with reduced ALDH2 activity owing to the rs671 polymorphism are at risk for neuropsychological impairments. A total of 139 PD patients were recruited. Each participant was assessed for medical characteristics and their ALDH2 genotype. The Mini-Mental State Examination (MMSE), the Clinical Dementia Rating Scale and the Frontal Behavioral Inventory were used to measure neuropsychological functions. We found that the MMSE scores were significantly lower in patients with inactive ALDH2 (U?=?1873.5, p?=?0.02). The presence of cognitive impairments was significantly more frequent in the inactive ALDH2 group (46.0%) than in the active ALDH2 group (26.3%) (?(2)?=?5.886, p?=?0.01). The inactive group showed significant deterioration in hobbies and exhibited more severe "disorganization" and "hyper-sexuality" behaviours. The additive effects of the allele on the development of cognitive impairments in PD patients may be an important finding that provides further insight into the pathogenic mechanism of cognitive dysfunction in PD.

SUBMITTER: Yu RL

PROVIDER: S-EPMC4958972 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Aldehyde dehydrogenase 2 is associated with cognitive functions in patients with Parkinson's disease.

Yu Rwei-Ling RL Tan Chun-Hsiang CH Lu Ying-Che YC Wu Ruey-Meei RM

Scientific reports 20160725

Neurotransmitter degradation has been proposed to cause the accumulation of neurotoxic metabolites. The metabolism of these metabolites involves aldehyde dehydrogenase 2 (ALDH2). The Asian-specific single nucleotide polymorphism rs671 causes reduced enzyme activity. This study aims to explore whether Parkinson's disease (PD) patients with reduced ALDH2 activity owing to the rs671 polymorphism are at risk for neuropsychological impairments. A total of 139 PD patients were recruited. Each particip ...[more]

PMID: 27453488

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Project description:BackgroundThere is growing evidence that the serotonergic system, in particular serotonin 2A receptors, is involved in neuropsychiatric symptoms in Parkinson's disease (PD), including cognitive processing and visual hallucinations. However, the relationship between serotonin 2A receptor availability, visual hallucinations, and cognitive profile is unknown. The objective of this study was to investigate the level of serotonin 2A receptor availability in brain regions affected by visual hallucinations and to test the association with cognitive/behavioral changes in patients who have PD with visual hallucinations.MethodsNondemented patients who had PD with (n = 11) and without (n = 8) visual hallucinations and age-matched controls (n = 10) were recruited. All participants completed neuropsychological testing, which consisted of visuoperceptual, executive, memory, language, and frontal-behavioral function. Positron emission tomography scans using [18F]setoperone, a serotonin 2A antagonist radioligand, were acquired in patients with PD, and a parametric binding potential map of [18F]setoperone was calculated with the simplified reference tissue model using the cerebellum as a reference.ResultsPatients who had PD with visual hallucinations exhibited significantly lower scores on measures of executive and visuoperceptual functions compared with age-matched controls. These changes were paralleled by decreased [18F]setoperone binding in the right insula, bilateral dorsolateral prefrontal cortex, right orbitofrontal cortex, right middle temporal gyrus, and right fusiform gyrus. The psychometric correlation analysis revealed significant relationships among tests associated with visuoperceptual function, memory and learning, and serotonin 2A binding in different prefrontal and ventral visual stream regions. There was also reduced serotonin 2A receptor binding in patients who had PD with depression.ConclusionsThese findings support a complex interaction between serotonin 2A receptor function and cognitive processing in patients who have PD with visual hallucinations.

Dataset Information

Aldehyde dehydrogenase 2 is associated with cognitive functions in patients with Parkinson's disease.

Publications

Aldehyde dehydrogenase 2 is associated with cognitive functions in patients with Parkinson's disease.

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