scholarly journals Free-water metrics in medial temporal lobe white matter tract projections relate to longitudinal cognitive decline

2020 ◽  
Author(s):  
Derek B. Archer ◽  
Elizabeth E. Moore ◽  
Niranjana Shashikumar ◽  
Logan Dumitrescu ◽  
Kimberly R. Pechman ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Executive Function ◽  
White Matter ◽  
Cognitive Decline ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Hippocampal Volume ◽  
White Matter Tract ◽  
Uncinate Fasciculus ◽  
Inferior Longitudinal Fasciculus

AbstractObjectiveHippocampal volume is a sensitive marker of neurodegeneration and a well-established predictor of age-related cognitive impairment. Recently, free-water (FW) magnetic resonance imaging (MRI) has shown associations with pathology in Alzheimer’s disease (AD), but it is still unclear whether these metrics are associated with measures of cognitive impairment. Here, we investigate whether FW and FW-corrected fractional anisotropy (FAT) within medial temporal lobe white matter tracts (cingulum, fornix, uncinate fasciculus, inferior longitudinal fasciculus, and tapetum) provides meaningful contribution to cognition and cognitive decline beyond hippocampal volume.Participants and MethodsVanderbilt Memory & Aging Project participants (n=319, 73±7 years, 59% male) with normal cognition and mild cognitive impairment (40% of cohort) underwent baseline brain MRI, including structural MRI to quantify hippocampal volume, diffusion MRI to quantify medial temporal lobe white matter tract FW and FAT, and longitudinal neuropsychological assessment with a mean follow-up of 3.5 years. Linear regressions were conducted to determine how hippocampal volume and white matter tract FW and FAT interact with baseline memory and executive function performances. Competitive model analyses determined the unique variance provided by white matter tract FW and FAT beyond that of hippocampal volume and other comorbidities. Linear mixed-effects models were conducted to determine how baseline hippocampal volume and white matter tract FW and FAT interact to explain longitudinal change in memory and executive function performances.ResultsFW in the inferior longitudinal fasciculus, tapetum, uncinate fasciculus, and cingulum were robustly associated with baseline memory and executive function. Further, competitive model analysis showed that tract FW contributed unique variance beyond other comorbidities and hippocampal volume for memory (ΔRadj2 range: 0.82-2.00%) and executive function (ΔRadj2 range: 0.88-1.87%). Longitudinal analyses demonstrated significant interactions of hippocampal volume and FAT in the inferior longitudinal fasciculus (p=0.02), tapetum (p=0.02), uncinate fasciculus (p=0.02), and cingulum (p=0.002) with decline in memory. For decline in executive function, we found significant interactions of hippocampal volume and FAT in inferior longitudinal fasciculus (p=0.03), tapetum (p=0.02), uncinate fasciculus (p=0.02), and fornix (p=0.02), as well as cingulum (p=0.02) and fornix (p=0.02) FW.ConclusionsOur results highlight novel associations between FW and FAT measures of medial temporal lobe tract microstructure and cognitive performance such that individuals with smaller hippocampal volumes and lower tract microstructure experience greater cognitive decline. These results suggest that white matter has a unique role in cognitive decline and, therefore, could be used to provide better disease staging, allowing for more precise disease monitoring in AD.

scholarly journals Free-water metrics in medial temporal lobe white matter tract projections relate to longitudinal cognitive decline

2020 ◽  
Vol 94 ◽  
pp. 15-23
Author(s):  
Derek B. Archer ◽  
Elizabeth E. Moore ◽  
Niranjana Shashikumar ◽  
Logan Dumitrescu ◽  
Kimberly R. Pechman ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Free Water ◽  
White Matter Tract

scholarly journals Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment

2019 ◽  
Vol 75 (7) ◽  
pp. 1382-1392 ◽  
Author(s):  
Marie Caillaud ◽  
Carol Hudon ◽  
Benjamin Boller ◽  
Simona Brambati ◽  
Simon Duchesne ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Episodic Memory ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Hippocampal Volume ◽  
Subjective Cognitive Decline

Abstract Objective The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer’s disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals. Method We included 126 participants from the Consortium for the Early Identification of Alzheimer’s disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs). Results Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups. Discussion As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD’s hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD.

006 Effect of apolipoprotein e ε4 allele on medial temporal lobe atrophy in ischaemic stroke patients

2018 ◽  
Vol 89 (6) ◽  
pp. A4.1-A4
Author(s):  
Mohamed Salah Khlif ◽  
Emilio Werden ◽  
Natalia Egorova ◽  
Wasim Khan ◽  
Amy Brodtmann
Keyword(s):  
Cognitive Impairment ◽  
Ischaemic Stroke ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Hippocampal Volume ◽  
Stroke Survivors ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
The Right ◽  
Time Point

IntroductionApolipoprotein E (APOE) ε4 allele is a known risk factor for the development of cognitive impairment. APOE ε4 carriers have been reported as having lower hippocampal volume in Alzheimer’s disease, mild cognitive impairment, and in healthy cohorts,1 but this is not well investigated in stroke. Here, we compared the regional volume in the medial temporal lobe in ischaemic stroke survivors, with and without the ε4 allele, three (time point 1, t1) and twelve (t2) months after stroke.Methods21 APOE ε4 carriers and 21 non-carriers, matched for lesion size and location and for neurological impairment as measured by NIHSS, were sampled from the CANVAS study, a longitudinal imaging study in stroke survivors.2 A mixed-effect linear model was used to analyse the effect of the ε4 allele on hippocampal, entorhinal, and para-hippocampal volumes, adjusting for age, sex, years of education, and total intracranial volume. Volumes were estimated using the longitudinal stream in FreeSurfer 5.3.ResultsThe left hippocampal (pt1=0.038, pt2=0.040) and entorhinal (pt1=0.044, pt2=0.038) volumes were significantly lower in the ε4-carrier group at each time point. The right entorhinal (pt1=pt2=0.002) and para-hippocampal (pt1=0.018, pt2=0.020) volumes were also significantly lower in the ε4-carrier group, but there was no difference in the right hippocampal volume (pt1=pt2=0.055) between the two groups. The group-time interaction was significant for the left para-hippocampal cortex (p=0.019): ε4 non-carriers showed a significant volume increase (p=0.018) between t1 and t2.ConclusionThese findings suggest that stroke survivors who carry the APOE-ε4 allele will experience greater atrophy in the medial temporal lobe in the twelve months following their stroke.References1. Manning EN, et al. e4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD. PLoS ONE2014;9(5):e97608.2. Brodtmann A, et al. Charting cognitive and volumetric trajectories after stroke: Protocol for the Cognition And Neocortical Volume After Stroke (CANVAS) study. Int J Stroke2014;9(6):824–828.

scholarly journals Diffusion Tensor Imaging in Alzheimer’s Disease and Mild Cognitive Impairment

2009 ◽  
Vol 21 (1-2) ◽  
pp. 39-49 ◽  
Author(s):  
G. T. Stebbins ◽  
C. M. Murphy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Entorhinal Cortex ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Diffusion Tensor

Structural magnetic resonance imaging (MRI) studies of Alzheimer’s disease and mild cognitive impairment (MCI) have focused on the hippocampus and entorhinal cortex; gray matter structures in the medial temporal lobe. Few studies have investigated the integrity of white matter in patients with AD or MCI. Diffusion tensor imaging (DTI) is a MRI technique that allows for the interrogation of the microstructural integrity of white matter. Based on increases in translational diffusion (mean diffusivity: MD) and decreases directional diffusion (fractional anisotropy: FA) damage to white matter can be assessed. Studies have identified regions of increased MD and decreased FA in patients with AD and MCI in all lobes of the brain, as well as medial temporal lobe structures including the hippocampus, entorhinal cortex and parahippocampal white matter. The pattern of white matter integrity disruption tends to follow an anterior to posterior gradient with greater damage noted in posterior regions in AD and MCI. Recent studies have exploited inter-voxel directional similarities to develop models of white matter pathways, and have used these models to assess the integrity of inter-cerebral connections. Particular focus has been applied to the parahippocampal white matter (including the perforant path) and the posterior cingulum. Although many studies have found DTI indicators of impaired white matter in AD and MCI, other studies have failed to detect any differences in MD or FA between the groups, demonstrating the need for large replicative studies. DTI is an evolving technique and advances in its application ought to provide new insights into AD and MCI.

scholarly journals White-matter tract integrity in late-life depression: associations with severity and cognition

2013 ◽  
Vol 44 (7) ◽  
pp. 1427-1437 ◽  
Author(s):  
R. A. Charlton ◽  
M. Lamar ◽  
A. Zhang ◽  
S. Yang ◽  
O. Ajilore ◽  
...  
Keyword(s):  
Executive Function ◽  
White Matter ◽  
Learning And Memory ◽  
Late Life ◽  
White Matter Integrity ◽  
White Matter Tract ◽  
Uncinate Fasciculus ◽  
Depression Severity ◽  
Late Life Depression ◽  
White Matter Tracts

BackgroundAlthough significant changes in both gray and white matter have been noted in late-life depression (LLD), the pathophysiology of implicated white-matter tracts has not been fully described. In this study we examined the integrity of specific white-matter tracts in LLD versus healthy controls (HC).MethodParticipants aged ⩾60 years were recruited from the community. The sample included 23 clinically diagnosed individuals with LLD and 23 HC. White-matter integrity metrics [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)] were calculated in the bilateral cingulum and uncinate fasciculus. Depression severity was measured using the Center for Epidemiological Studies Depression Scale (CESD). Composite scores for learning and memory and executive function were created using standardized neuropsychological assessments.ResultsWhite-matter integrity was lower in LLD versus HC in the bilateral cingulum and right uncinate fasciculus (p⩽0.05). In the whole sample, depression severity correlated with integrity in the bilateral cingulum and right uncinate fasciculus (p ⩽0.05). In patients, depression severity correlated with the integrity of the left uncinate fasciculus (p = 0.03); this tract also correlated with executive function (p = 0.02). Among HC, tract integrity did not correlate with depression scores; however, learning and memory correlated with integrity of the bilateral uncinate fasciculus and bilateral cingulum; executive function correlated with the right uncinate and left cingulum (p ⩽0.05).ConclusionsWhite-matter tract integrity was lower in LLD than in HC and was associated with depression severity across all participants. Tract integrity was associated with cognition in both groups but more robustly among HC.

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