What can DTI tell about early cognitive impairment? – Differentiation between MCI subtypes and healthy controls by diffusion tensor imaging

Gyebnár, Gyula; Szabó, Ádám; Sirály, Enikö; Fodor, Zsuzsanna; Sákovics, Anna; Salacz, Pál; Hidasi, Zoltán; Csibri, Éva; Rudas, Gábor; Kozák, Lajos R.; Csukly, Gábor

doi:10.1016/j.pscychresns.2017.10.007

Cited by 39 publications

(34 citation statements)

References 65 publications

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“…The Isaacs set test is a multi-composite test involving executive processing strategy allowing efficient search within the semantic stores (Amieva et al, 2008;Catheline et al, 2015). The observed association is consistent with previous studies that evidenced the involvement of the cingulum bundle in executive functioning (Bettcher et al, 2016;Gyebnár et al, 2018;Metzler-Baddeley et al, 2012;Seiler et al, 2018) and with studies showing that higher free water fraction was associated with poorer cognitive performance in older adults (Maillard et al, 2019) and in clinical populations (Bergamino et al, 2017;Ji et al, 2017Ji et al, , 2019Maillard et al, 2017). Indeed, in a recent longitudinal study on 224 elderly subjects, Maillard and colleagues showed that free water increased was not only associated with reduced performance in executive function but was also the most robust predictor of cognitive decline (Maillard et al, 2019).…”

Section: Free Water Contentsupporting

confidence: 86%

Diffusion MRI free water is a sensitive marker of age-related changes in the cingulum

Edde

Theaud

Rheault

et al. 2019

Preprint

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Diffusion MRI is extensively used to investigate changes in white matter microstructure. However, diffusion measures within white matter tissue can be affected by partial volume effects due to cerebrospinal fluid and white matter hyperintensities, especially in the aging brain. In previous aging studies, the cingulum bundle that plays a central role in the architecture of the brain networks supporting cognitive functions has been associated with cognitive deficits. However, most of these studies did not consider the partial volume effects on diffusion measures. The aim of this study was to evaluate the effect of free water elimination on diffusion measures of the cingulum in a group of 68 healthy elderly individuals. We first determined the effect of free water elimination on conventional DTI measures and then examined the effect of free water elimination on verbal fluency performance over 12 years. The cingulum bundle was reconstructed with a tractography pipeline including a white matter hyperintensities mask to limit the negative impact of hyperintensities on fiber tracking algorithms. We observed that free water elimination improved the sensitivity of conventional DTI measures to detect associations between tissue-specific diffusion measures of the cingulum and changes in verbal fluency in older individuals. Moreover, free water content measured along the cingulum was independently strongly associated with changes in verbal fluency. These observations suggest the importance of using free water elimination when studying brain aging and indicate that free water itself could be a relevant marker for age-related cingulum white matter modifications and cognitive decline.

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Section: Free Water Contentsupporting

confidence: 86%

Diffusion MRI free water is a sensitive marker of age-related changes in the cingulum

Edde

Theaud

Rheault

et al. 2019

Preprint

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“…While AD is a disease primarily associated with GM loss, the WM changes in different brain regions have also been reported with a role in cognitive expression (Dore et al, 2013). Supportive studies using diffusion tensor imaging metrics to characterize brain WM reported an association between fiber density and memory (Gyebnar et al, 2018;Remy, Vayssiere, Saint-Aubert, Barbeau, & Pariente, 2015) with reduced brain volume in PCC region and with worsened memory in aMCI (Meyer et al, 2013). These morphometric studies of CC region for its involvement in cognitive processes have also been investigated and found supportive of other functional, directional, and psychological studies in a clinical setting.…”

Section: Significance Of Cingulate Region In Cognitive Functioningmentioning

confidence: 99%

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

Shukla

Mandal

Tripathi

et al. 2019

Human Brain Mapping

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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.

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“… Peter, et al 2016 [21] 20 MCI, 20 CNC Verbal Learning and Memory Test HC and basal forebrain cholinergic system volumetry HC volume positively correlated with memory. Gyebnar, et al 2018 [22] 18 aMCI, 20 naMCI, 27 CNC CANTAB, RAVLT Voxel- and ROI-based DTI Voxel-based: R inferior frontal gyrus pars triangularis FA negatively correlated with visual memory. L parahippocampal gyrus MD negatively correlated with verbal memory.…”

Section: Structural Mrimentioning

confidence: 99%

“…Similar to GM changes, which include both MTL and extratemporal regions, precuneus WM volume reduction was also associated with worsened memory in aMCI [18] . Several fasciculi including uncinate, fornix, and cingulum, which are connected to medial temporal regions, were implicated in studies associating fiber density and memory [20] , [22] , [41] . In addition to these WM volume and integrity changes, Fujishima et al [19] reported that increased number of WMHs, pointing to increased vascular impairment, in the bilateral periventricular regions was related to worse recall performance in MCI.…”

Section: Structural Mrimentioning

confidence: 99%

Current understanding of magnetic resonance imaging biomarkers and memory in Alzheimer's disease

Bayram

Caldwell

Banks

2018

A&D Transl Res & Clin Interv

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Alzheimer's disease (AD) is caused by a cascade of changes to brain integrity. Neuroimaging biomarkers are important in diagnosis and monitoring the effects of interventions. As memory impairments are among the first symptoms of AD, the relationship between imaging findings and memory deficits is important in biomarker research. The most established magnetic resonance imaging (MRI) finding is hippocampal atrophy, which is related to memory decline and currently used as a diagnostic criterion for AD. While the medial temporal lobes are impacted early by the spread of neurofibrillary tangles, other networks and regional changes can be found quite early in the progression. Atrophy in several frontal and parietal regions, cortical thinning, and white matter alterations correlate with memory deficits in early AD. Changes in activation and connectivity have been detected by functional MRI (fMRI). Task-based fMRI studies have revealed medial temporal lobe hypoactivation, parietal hyperactivation, and frontal hyperactivation in AD during memory tasks, and activation patterns of these regions are also altered in preclinical and prodromal AD. Resting state fMRI has revealed alterations in default mode network activity related to memory in early AD. These studies are limited in part due to the historic inclusion of patients who had suspected AD but likely did not have the disorder. Modern biomarkers allow for more diagnostic certainty, allowing better understanding of neuroimaging markers in true AD, even in the preclinical stage. Larger patient cohorts, comparison of candidate imaging biomarkers to more established biomarkers, and inclusion of more detailed neuropsychological batteries to assess multiple aspects of memory are needed to better understand the memory deficit in AD and help develop new biomarkers. This article reviews MRI findings related to episodic memory impairments in AD and introduces a new study with multimodal imaging and comprehensive neuropsychiatric evaluation to overcome current limitations.

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What can DTI tell about early cognitive impairment? – Differentiation between MCI subtypes and healthy controls by diffusion tensor imaging

Cited by 39 publications

References 65 publications

Diffusion MRI free water is a sensitive marker of age-related changes in the cingulum

Diffusion MRI free water is a sensitive marker of age-related changes in the cingulum

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

Current understanding of magnetic resonance imaging biomarkers and memory in Alzheimer's disease

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