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White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers

Background: Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. Objectiv...

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Autores principales: Besga, Ariadna, Chyzhyk, Darya, Gonzalez-Ortega, Itxaso, Echeveste, Jon, Graña-Lecuona, Marina, Graña, Manuel, Gonzalez-Pinto, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472694/
https://www.ncbi.nlm.nih.gov/pubmed/28670271
http://dx.doi.org/10.3389/fnagi.2017.00179
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author Besga, Ariadna
Chyzhyk, Darya
Gonzalez-Ortega, Itxaso
Echeveste, Jon
Graña-Lecuona, Marina
Graña, Manuel
Gonzalez-Pinto, Ana
author_facet Besga, Ariadna
Chyzhyk, Darya
Gonzalez-Ortega, Itxaso
Echeveste, Jon
Graña-Lecuona, Marina
Graña, Manuel
Gonzalez-Pinto, Ana
author_sort Besga, Ariadna
collection PubMed
description Background: Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. Objectives: We look for WM tract voxel clusters showing significant differences when comparing of AD vs. LOBD, and its correlations with systemic blood plasma biomarkers (inflammatory, neurotrophic factors, and oxidative stress). Materials: A sample of healthy controls (HC) (n = 19), AD patients (n = 35), and LOBD patients (n = 24) was recruited at the Alava University Hospital. Blood plasma samples were obtained at recruitment time and analyzed to extract the inflammatory, oxidative stress, and neurotrophic factors. Several modalities of MRI were acquired for each subject, Methods: Fractional anisotropy (FA) coefficients are obtained from diffusion weighted imaging (DWI). Tract based spatial statistics (TBSS) finds FA skeleton clusters of WM tract voxels showing significant differences for all possible contrasts between HC, AD, and LOBD. An ANOVA F-test over all contrasts is carried out. Results of F-test are used to mask TBSS detected clusters for the AD > LOBD and LOBD > AD contrast to select the image clusters used for correlation analysis. Finally, Pearson's correlation coefficients between FA values at cluster sites and systemic blood plasma biomarker values are computed. Results: The TBSS contrasts with by ANOVA F-test has identified strongly significant clusters in the forceps minor, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and cingulum gyrus. The correlation analysis of these tract clusters found strong negative correlation of AD with the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) blood biomarkers. Negative correlation of AD and positive correlation of LOBD with inflammation biomarker IL6 was also found. Conclusion: TBSS voxel clusters tract atlas localizations are consistent with greater behavioral impairment and mood disorders in LOBD than in AD. Correlation analysis confirms that neurotrophic factors (i.e., NGF, BDNF) play a great role in AD while are absent in LOBD pathophysiology. Also, correlation results of IL1 and IL6 suggest stronger inflammatory effects in LOBD than in AD.
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spelling pubmed-54726942017-06-30 White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers Besga, Ariadna Chyzhyk, Darya Gonzalez-Ortega, Itxaso Echeveste, Jon Graña-Lecuona, Marina Graña, Manuel Gonzalez-Pinto, Ana Front Aging Neurosci Neuroscience Background: Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. Objectives: We look for WM tract voxel clusters showing significant differences when comparing of AD vs. LOBD, and its correlations with systemic blood plasma biomarkers (inflammatory, neurotrophic factors, and oxidative stress). Materials: A sample of healthy controls (HC) (n = 19), AD patients (n = 35), and LOBD patients (n = 24) was recruited at the Alava University Hospital. Blood plasma samples were obtained at recruitment time and analyzed to extract the inflammatory, oxidative stress, and neurotrophic factors. Several modalities of MRI were acquired for each subject, Methods: Fractional anisotropy (FA) coefficients are obtained from diffusion weighted imaging (DWI). Tract based spatial statistics (TBSS) finds FA skeleton clusters of WM tract voxels showing significant differences for all possible contrasts between HC, AD, and LOBD. An ANOVA F-test over all contrasts is carried out. Results of F-test are used to mask TBSS detected clusters for the AD > LOBD and LOBD > AD contrast to select the image clusters used for correlation analysis. Finally, Pearson's correlation coefficients between FA values at cluster sites and systemic blood plasma biomarker values are computed. Results: The TBSS contrasts with by ANOVA F-test has identified strongly significant clusters in the forceps minor, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and cingulum gyrus. The correlation analysis of these tract clusters found strong negative correlation of AD with the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) blood biomarkers. Negative correlation of AD and positive correlation of LOBD with inflammation biomarker IL6 was also found. Conclusion: TBSS voxel clusters tract atlas localizations are consistent with greater behavioral impairment and mood disorders in LOBD than in AD. Correlation analysis confirms that neurotrophic factors (i.e., NGF, BDNF) play a great role in AD while are absent in LOBD pathophysiology. Also, correlation results of IL1 and IL6 suggest stronger inflammatory effects in LOBD than in AD. Frontiers Media S.A. 2017-06-16 /pmc/articles/PMC5472694/ /pubmed/28670271 http://dx.doi.org/10.3389/fnagi.2017.00179 Text en Copyright © 2017 Besga, Chyzhyk, Gonzalez-Ortega, Echeveste, Graña-Lecuona, Graña and Gonzalez-Pinto. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Besga, Ariadna
Chyzhyk, Darya
Gonzalez-Ortega, Itxaso
Echeveste, Jon
Graña-Lecuona, Marina
Graña, Manuel
Gonzalez-Pinto, Ana
White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers
title White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers
title_full White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers
title_fullStr White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers
title_full_unstemmed White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers
title_short White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers
title_sort white matter tract integrity in alzheimer's disease vs. late onset bipolar disorder and its correlation with systemic inflammation and oxidative stress biomarkers
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472694/
https://www.ncbi.nlm.nih.gov/pubmed/28670271
http://dx.doi.org/10.3389/fnagi.2017.00179
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