Dataset Information

Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease.

ABSTRACT: Cognitive dysfunction is one of the most typical characteristics in various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (advanced stage). Although several mechanisms like neuronal apoptosis and inflammatory responses have been recognized to be involved in the pathogenesis of cognitive dysfunction in these diseases, recent studies on neurodegeneration and cognitive dysfunction have demonstrated a significant impact of receptor modulation on cognitive changes. The pathological alterations in various receptors appear to contribute to cognitive impairment and/or deterioration with correlation to diversified mechanisms. This article recapitulates the present understandings and concepts underlying the modulation of different receptors in human beings and various experimental models of Alzheimer's disease and Parkinson's disease as well as a conceptual update on the underlying mechanisms. Specific roles of serotonin, adrenaline, acetylcholine, dopamine receptors, and N-methyl-D-aspartate receptors in Alzheimer's disease and Parkinson's disease will be interactively discussed. Complex mechanisms involved in their signaling pathways in the cognitive dysfunction associated with the neurodegenerative diseases will also be addressed. Substantial evidence has suggested that those receptors are crucial neuroregulators contributing to cognitive pathology and complicated correlations exist between those receptors and the expression of cognitive capacities. The pathological alterations in the receptors would, therefore, contribute to cognitive impairments and/or deterioration in Alzheimer's disease and Parkinson's disease. Future research may shed light on new clues for the treatment of cognitive dysfunction in neurodegenerative diseases by targeting specific alterations in these receptors and their signal transduction pathways in the frontal-striatal, fronto-striato-thalamic, and mesolimbic circuitries.

SUBMITTER: Xu Y

PROVIDER: S-EPMC3371373 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease.

Xu Yunqi Y Yan Junqiang J Zhou Peng P Li Jiejie J Gao Huimin H Xia Ying Y Wang Qing Q

Progress in neurobiology 20120225 1

Cognitive dysfunction is one of the most typical characteristics in various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (advanced stage). Although several mechanisms like neuronal apoptosis and inflammatory responses have been recognized to be involved in the pathogenesis of cognitive dysfunction in these diseases, recent studies on neurodegeneration and cognitive dysfunction have demonstrated a significant impact of receptor modulation on cognitive changes. Th ...[more]

PMID: 22387368

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Project description:IntroductionAccurate early diagnosis of Parkinson's disease is hampered by its long prodromal period and the variable manifestations of its motor symptoms. While olfactory dysfunction can occur before motor-symptom onset and serve as a non-disease-specific diagnostic aid, its underlying causes are incompletely understood.MethodsCorrelation analyses, univariate density estimates, ANOVA and regression evaluated relationships between scores on the Montreal Cognitive Assessment and Hopkins Verbal Learning Test and those on the University of Pennsylvania Smell Identification Test in 1280 Parkinson's Progression Markers Initiative subjects placed into five diagnostic categories. Structural equation modeling identified cognitive measures having significant indirect effects on olfactory-function-test scores.ResultsGlobal cognition, verbal learning and memory, attention, delayed-recall, and visuospatial/executive function scores show weak-to-moderate, significant associations with olfactory-function-test scores. Associations are stronger in symptomatic than asymptomatic subjects having mutations in LRRK2, GBA or SNCA. Score distributions are nonuniform across diagnostic categories. Linear regression found that all cognitive measures except attention predicted olfactory-function-test scores. Three structural equation models assessing indirect effects of verbal learning/memory with either global cognition, visuospatial/executive function, or delayed-recall had a good statistical fit to the data. Only verbal learning/memory scores significantly help explain olfactory-function-test scores in all symptomatic diagnostic categories (-0.56 < b < -0.23, 0.001 < P < .005). Visuospatial/executive-function test scores help explain olfactory-function-test scores in both genetic Parkinson's disease diagnostic categories (-0.25 < b < -0.17, 0.032 < P < .033).ConclusionImpaired verbal learning/memory and visuospatial/executive function contributes to lower performance on olfactory function tests in Parkinson's disease. As both of these domains impact decision-making, decision-making in turn may impact olfactory assessment in Parkinson's disease.

Project description:Background: Quantitative electroencephalography (qEEG) has been suggested as a biomarker for cognitive decline in Parkinson's disease (PD). Objective: Determine if applying a wavelet-based qEEG algorithm to 21-electrode, resting-state EEG recordings obtained in a routine clinical setting has utility for predicting cognitive impairment in PD. Methods: PD subjects, evaluated by disease stage and motor score, were compared to healthy controls (N = 20 each). PD subjects with normal (PDN, MoCA 26-30, N = 6) and impaired (PDD, MoCA ≤ 25, N = 14) cognition were compared. The wavelet-transform based time-frequency algorithm assessed the instantaneous predominant frequency (IPF) at 60 ms intervals throughout entire recordings. We then determined the relative time spent by the IPF in the four standard EEG frequency bands (RTF) at each scalp location. The resting occipital rhythm (ROR) was assessed using standard power spectral analysis. Results: Comparing PD subjects to healthy controls, mean values are decreased for ROR and RTF-Beta, greater for RTF-Theta and similar for RTF-Delta and RTF-Alpha. In logistic regression models, arithmetic combinations of RTF values [e.g., (RTF-Alpha) + (RTF-Beta)/(RTF-Delta + RTF-Theta)] and RTF-Alpha values at occipital or parietal locations are most able to discriminate between PD and controls. A principal component (PC) from principal component analysis (PCA) using RTF-band values in all subjects is associated with PD status (p = 0.004, β = 0.31, AUC = 0.780). Its loadings show positive contribution from RTF-Theta at all scalp locations, and negative contributions from RTF-Beta at occipital, parietal, central, and temporal locations. Compared to cognitively normal PD subjects, cognitively impaired PD subjects have lower median RTF-Alpha and RTF-Beta values, greater RTF-Theta values and similar RTF-Delta values. A PC from PCA using RTF-band values in PD subjects is associated with cognitive status (p = 0.002, β = 0.922, AUC = 0.89). Its loadings show positive contributions from RTF-Theta at all scalp locations, negative contributions from RTF-Beta at central locations, and negative contributions from RTF-Delta at central, frontal and temporal locations. Age, disease duration and/or sex are not significant covariates. No PC was associated with motor score or disease stage. Significance: Analyzing standard EEG recordings obtained in a community practice setting using a wavelet-based qEEG algorithm shows promise as a PD biomarker and for predicting cognitive impairment in PD.

Dataset Information

Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease.

Publications

Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease.

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