Dataset Information

Microstructural network alterations of olfactory dysfunction in newly diagnosed Parkinson's disease.

ABSTRACT: Olfactory dysfunction is a robust and early sign for Parkinson's disease (PD). Previous studies have revealed its association with dementia and related neural changes in PD. Yet, how olfactory dysfunction affects white matter (WM) microstructure in newly diagnosed and untreated PD remains unclear. Here we comprehensively examined WM features using unbiased whole-brain analyses. 88 newly diagnosed PD patients without dementia (70 with hyposmia and 18 without hyposmia) and 33 healthy controls underwent clinical assessment and diffusion tensor imaging (DTI) scanning. Tract-based special statistics (TBSS), graph-theoretic methods and network-based statistics (NBS) were used to compare regional and network-related WM features between groups. TBSS analysis did not show any differences in fractional anisotropy and mean diffusivity between groups. Compared with controls, PD patients without hyposmia showed a significant decrease in global efficiency, whilst PD patients with hyposmia exhibited significantly reduced global and local efficiency and additionally a disrupted connection between the right medial orbitofrontal cortex and left rectus and had poorer frontal-related cognitive functioning. These results demonstrate that hyposmia-related WM changes in early PD only occur at the network level. The confined disconnectivity between the bilateral olfactory circuitry may serve as a biomarker for olfactory dysfunction in early PD.

SUBMITTER: Wen MC

PROVIDER: S-EPMC5624890 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Microstructural network alterations of olfactory dysfunction in newly diagnosed Parkinson's disease.

Wen Ming-Ching MC Xu Zheyu Z Lu Zhonghao Z Chan Ling Ling LL Tan Eng King EK Tan Louis C S LCS

Scientific reports 20171002 1

Olfactory dysfunction is a robust and early sign for Parkinson's disease (PD). Previous studies have revealed its association with dementia and related neural changes in PD. Yet, how olfactory dysfunction affects white matter (WM) microstructure in newly diagnosed and untreated PD remains unclear. Here we comprehensively examined WM features using unbiased whole-brain analyses. 88 newly diagnosed PD patients without dementia (70 with hyposmia and 18 without hyposmia) and 33 healthy controls unde ...[more]

PMID: 28970540

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Project description:BackgroundCognitive impairment is a common non-motor symptom in patients with Parkinson's disease (PD). Mild cognitive impairment (MCI) is also prevalent in nondemented PD patients, even in newly diagnosed PD patients. The possible impacts of MCI on brain function activities for PD patients need more investigation, and the potential of emerging technologies for detecting underlying pathophysiology of cognitive signs in PD can be further improved.MethodForty-seven newly diagnosed drug-naïve PD patients (28 PD-MCI patients and 19 PD patients with cognitively unimpaired (PD-CU)) and 28 healthy controls (HCs) underwent resting-state functional MRI. The connectivity patterns of specific networks were investigated through the independent component analysis among PD-MCI, PD-CU and HCs groups.ResultsThe independent component analysis revealed significantly decreased functional connectivity (FC) of the default mode network, visual network and sensorimotor network in the PD-MCI subgroup compared with the HC group. Furthermore, FC of the default mode network was positively correlated with memory scores from the brief visuospatial memory test-revised, and FC of the visual network was positively correlated with visuospatial scores from the clock copying test in the PD-MCI group. In all patients with PD, FC of the sensorimotor network negatively correlated with motor severity scores from the Unified PD Rating Scale (UPDRS) part III. On the other hand, the potential damage was more likely to occur in FC between the sensorimotor network and limbic network, and between the ventral attention network and visual network in all PD patients.ConclusionsNewly diagnosed drug-naïve PD-MCI patients showed characteristic damage of FC within the default mode network, visual network and sensorimotor network, and all PD patients presented impaired FC between the sensorimotor network and limbic network, and FC between the ventral attention network and visual network. These network-wide functional aberrations may underline the pathophysiology of PD.

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:ObjectiveThe objective of this study was to develop valid prognostic models to predict mortality, dependency, and "death or dependency" for use in newly diagnosed Parkinson's disease (PD).MethodsThe models were developed in the Parkinsonism Incidence in North-East Scotland study (UK, 198 patients) and validated in the ParkWest study (Norway, 192 patients), cohorts that attempted to identify and follow-up all new PD cases in the study area. Dependency was defined using the Schwab & England scale. We selected variables measured at time of diagnosis to include in the models. Internal validation and external validation were performed by calculating C-statistics (discrimination) and plotting observed versus predicted risk in quantiles of predicted risk (calibration).ResultsOlder age, male sex, increased severity of axial features, and Charlson comorbidity index were independent prognostic factors in the mortality model. Increasing age, higher smoking history, increased severity of axial features, and lower MMSE score were independent predictors in the models of dependency and "death or dependency." Each model had very good internal calibration and very good or good discrimination (internal and external C-statistics for the models were 0.73-0.75 and 0.68-0.78, respectively). Although each model clearly separated patients into groups according to risk, they tended to overestimate risk in ParkWest. The models were recalibrated to the baseline risk in the ParkWest study and then calibrated well in this cohort.ConclusionsWe have developed prognostic models for predicting medium-term risk of important clinical outcomes in newly diagnosed PD. These models have validity for use for stratification of randomization, confounder adjustment, and case-mix correction, but they are inadequate for individualized prognostication. © 2017. The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Project description:Objective: To conduct an investigation into the reliability of assessing the olfactory function of patients with Parkinson's disease (PD) in a clinical setting of crowding patients in populated countries, such as China, by the hyposmia rating scale (HRS) and compare other non-motor features between patients with PD with olfactory dysfunction (PD-OD) and patients with PD without olfactory dysfunction (PD-NOD), according to the result of olfactory function assessed by the Sniffin' Sticks test. Methods: A total of 320 patients with clinically confirmed or clinically possible PD were recruited. Olfactory function of all participants was assessed with the HRS and the Sniffin' Sticks test. Demographic data and clinical information were collected, and patients were evaluated using standardized assessment protocols. With reference to the Sniffin' Sticks test, the specificity, sensitivity, coincidence rate, and kappa value of the HRS was computed, and then its reliability was evaluated. We divided patients into PD-OD and PD-NOD groups based on the results of olfactory function assessed by the Sniffin' Sticks test. Clinical manifestations were compared between PD-OD and PD-NOD. Results: The percentage of patients with OD determined by the Sniffin' Sticks test was 65.6%, and the percentage of those with OD was 55.6% when using the HRS measured olfactory function. With reference to the Sniffin' Sticks test, the specificity, sensitivity, coincidence rate, and kappa value of the HRS were 82.73, 75.71, 78.13%, and 0.55, respectively. The area under the receiver operating characteristic curve for the HRS was 0.793. There were no differences in demographic characteristics between the PD-OD and PD-NOD groups. The patients with hyposmia had more severe non-motor symptoms. Conclusion: The HRS is of great value as a self-assessment scale for evaluating olfactory function, especially in PD patients over 55 years old. Moreover, PD patients with hyposmia have more severe non-motor features than PD patients without hyposmia, mainly in terms of mood and constipation.

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Microstructural network alterations of olfactory dysfunction in newly diagnosed Parkinson's disease.

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Microstructural network alterations of olfactory dysfunction in newly diagnosed Parkinson's disease.

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