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Quantitation of in vivo brain glutathione conformers in cingulate cortex among age-matched control, MCI, and AD patients using MEGA-PRESS.

ABSTRACT: Oxidative stress (OS) plays an important role in Alzheimer's disease (AD) and glutathione (GSH) mitigates this effect by maintaining redox-imbalance and free-radical neutralization. Quantified brain GSH concentration provides distinct information about OS among age-matched normal control (NC), mild cognitive impairment (MCI) and AD patients. We report alterations of in vivo GSH conformers, along with the choline, creatine, and N-acetylaspartate levels in the cingulate cortex (CC) containing anterior (ACC) and posterior (PCC) regions of 64 (27 NC, 19 MCI, and 18 AD) participants using MEscher-GArwood-Point-RESolved spectroscopy sequence. Result indicated, tissue corrected GSH depletion in PCC among MCI (p = .001) and AD (p = .028) and in ACC among MCI (p = .194) and AD (p = .025) as compared to NC. Effects of the group, region, and group?×?region on GSH with age and gender as covariates were analyzed using a generalized linear model with Bonferroni correction for multiple comparisons. A significant effect of group with GSH depletion in AD and MCI was observed as compared to NC. Receiver operator characteristic (ROC) analysis of GSH level in CC differentiated between MCI and NC groups with an accuracy of 82.8% and 73.5% between AD and NC groups. Multivariate ROC analysis for the combined effect of the GSH alteration in both ACC and PCC regions provided improved diagnostic accuracy of 86.6% for NC to MCI conversion and 76.4% for NC to AD conversion. We conclude that only closed GSH conformer depletion in the ACC and PCC regions is critical and constitute a potential biomarker for AD.

SUBMITTER: Shukla D

PROVIDER: S-EPMC7268069 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Quantitation of in vivo brain glutathione conformers in cingulate cortex among age-matched control, MCI, and AD patients using MEGA-PRESS.

Shukla Deepika D Mandal Pravat Kumar PK Tripathi Manjari M Vishwakarma Gayatri G Mishra Ritwick R Sandal Kanika K

Human brain mapping 20191004 1

Oxidative stress (OS) plays an important role in Alzheimer's disease (AD) and glutathione (GSH) mitigates this effect by maintaining redox-imbalance and free-radical neutralization. Quantified brain GSH concentration provides distinct information about OS among age-matched normal control (NC), mild cognitive impairment (MCI) and AD patients. We report alterations of in vivo GSH conformers, along with the choline, creatine, and N-acetylaspartate levels in the cingulate cortex (CC) containing ante ...[more]

PMID: 31584232

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Project description:INTRODUCTION:The diagnosis of mild cognitive impairment (MCI) refers to cognitive impairment not meeting dementia criteria. A survey among members of the American Association of Neurology (AAN) showed that MCI was considered a useful diagnosis. Recently, research criteria have been proposed for the diagnosis of Alzheimer's disease (AD) in MCI based on AD biomarkers (prodromal AD/MCI due to AD). The aim of this study was to investigate the attitudes of clinicians in Europe on the clinical utility of MCI and prodromal AD/MCI due to AD criteria. We also investigated whether the prodromal AD/MCI due to AD criteria impacted management of MCI patients. METHODS:An online survey was performed in 2015 among 102 members of the European Academy of Neurology (EAN) and the European Alzheimer's Disease Consortium (EADC). Questions were asked on how often criteria were used, how they were operationalized, how they changed patient management, and what were considered advantages and limitations of MCI and prodromal AD/MCI due to AD. The questionnaire consisted of 47 questions scored on a Likert scale. RESULTS:Almost all respondents (92%) used the MCI diagnosis in clinical practice. Over 80% of the EAN/EADC respondents found a MCI diagnosis useful because it helped to label the cognitive problem, involve patients in planning for the future, and start risk reduction activities. These findings were similar to those reported in the AAN survey. Research criteria for prodromal AD/MCI due to AD were used by 68% of the EAN/EADC respondents. The most common reasons to use the criteria were increased certainty of diagnosis (86%), increased possibilities to provide counseling (51%), facilitation of follow-up planning (48%), start of medical intervention (49%), and response to patients' wish for a diagnosis (41%). Over 70% of the physicians considered that a diagnosis of prodromal AD/MCI due to AD had an added value over the MCI diagnosis. CONCLUSIONS:The diagnostic criteria of MCI and prodromal AD/MCI due to AD are commonly used among EAN/EADC members. The prodromal AD/MCI due to AD were considered clinically useful and impacted patient management and communication.

Dataset Information

Quantitation of in vivo brain glutathione conformers in cingulate cortex among age-matched control, MCI, and AD patients using MEGA-PRESS.

Publications

Quantitation of in vivo brain glutathione conformers in cingulate cortex among age-matched control, MCI, and AD patients using MEGA-PRESS.

Similar Datasets

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