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

ABSTRACT: Although hippocampal volume has served as a long-standing predictor of cognitive decline, diffusion magnetic resonance imaging studies of white matter have shown similar relationships. Still, it remains unclear if gray matter and white matter interact to predict cognitive impairment and longitudinal decline. Here, we investigate whether free-water (FW) and FW-corrected fractional anisotropy (FA_T) within medial temporal lobe white matter tracts provides meaningful contribution to cognition and cognitive decline beyond hippocampal volume. Using data from the Vanderbilt Memory & Aging Project (n = 319), we found that FW was associated with baseline memory and executive function beyond that of hippocampal volume and other comorbidities. Longitudinal analyses demonstrated significant interactions of hippocampal volume and inferior longitudinal fasciculus (p = 0.043) and cingulum bundle (p = 0.025) FA_T on memory decline and with fornix FA_T (p = 0.025) on decline in executive function. Results suggest that FW metrics of white matter have a unique role in cognitive decline and should be included in theoretical models of aging, cerebrovascular disease, and Alzheimer's disease.

SUBMITTER: Archer DB

PROVIDER: S-EPMC7483422 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Archer Derek B DB Moore Elizabeth E EE Shashikumar Niranjana N Dumitrescu Logan L Pechman Kimberly R KR Landman Bennett A BA Gifford Katherine A KA Jefferson Angela L AL Hohman Timothy J TJ

Neurobiology of aging 20200512

Although hippocampal volume has served as a long-standing predictor of cognitive decline, diffusion magnetic resonance imaging studies of white matter have shown similar relationships. Still, it remains unclear if gray matter and white matter interact to predict cognitive impairment and longitudinal decline. Here, we investigate whether free-water (FW) and FW-corrected fractional anisotropy (FA<sub>T</sub>) within medial temporal lobe white matter tracts provides meaningful contribution to cogni ...[more]

PMID: 32502831

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Project description:Mesial temporal lobe epilepsy (MTLE), one of the most common types of refractory focal epilepsy, has shown white matter abnormalities both within and beyond the temporal lobe. In particular, the white matter abnormalities in the ipsilateral hemisphere are more obvious than those in the contralateral hemisphere in MTLE, that is, the abnormalities present asymmetrical characteristics. However, very few studies have characterized the white matter microstructure asymmetry in MTLE patients specifically. Thus, we performed diffusion tensor imaging (DTI) to investigate the white matter microstructure asymmetries of patients with MTLE with unilateral hippocampal sclerosis (MTLE-HS). We enrolled 25 MTLE-HS (left MTLE-HS group, n = 13; right MTLE-HS group, n = 12) and 26 healthy controls (HC). DTI data were analyzed by tract-based spatial statistics (TBSS) to test the hemispheric differences across the entire white matter skeleton. We also conducted a two-sample paired t-test for 21 paired region of interests (ROIs) parceled on the basis of the ICBM-DTI-81 white-matter label atlas of bilateral hemispheres to test the hemispheric differences. An asymmetry index (AI) was calculated to further quantify the differences between the left and right paired-ROIs. It was found that the asymmetries of white matter skeletons were significantly lower in the MTLE-HS groups than in the HC group. In particular, the asymmetry traits were moderately reduced in the RMTLE-HS group and obviously reduced in the LMTLE-HS group. In addition, AI was significantly different in the RMTLE-HS group from the LMTLE-HS or HC group in the limbic system and superior longitudinal fasciculus (SLF). The current study found that the interhemispheric white matter asymmetries were significantly reduced in the MTLE-HS groups than in the HC group. The interhemispheric white matter asymmetries are distinctly affected in left and right MTLE-HS groups. The differences in AI among RMTLE-HS, LMTLE-HS, and HC involved the limbic system and SLF, which may have some pragmatic implications for the diagnosis of MTLE and differentiating LMTLE-HS from RMTLE-HS.

Project description:ObjectiveTemporal Lobe Epilepsy (TLE) is frequently a neurodevelopmental disorder, involving subcortical volume loss, cortical atrophy, and white matter (WM) disruption. However, few studies have addressed how these pathological changes in TLE relate to one another. In this study, we investigate spatial patterns of gray and white matter degeneration in TLE and evaluate the hypothesis that the relationship among these patterns varies as a function of the age at which seizures begin.MethodsEighty-two patients with TLE and 59 healthy controls were enrolled. T1-weighted images were used to obtain hippocampal volumes and cortical thickness estimates. Diffusion-weighted imaging was used to obtain fractional anisotropy (FA) and mean diffusivity (MD) of the superficial WM (SWM) and deep WM tracts. Analysis of covariance was used to examine patterns of WM and gray matter alterations in TLE relative to controls, controlling for age and sex. Sliding window correlations were then performed to examine the relationships between SWM degeneration, cortical thinning, and hippocampal atrophy across ages of seizure onset.ResultsCortical thinning in TLE followed a widespread, bilateral pattern that was pronounced in posterior centroparietal regions, whereas SWM and deep WM loss occurred mostly in ipsilateral, temporolimbic regions compared to controls. Window correlations revealed a relationship between hippocampal volume loss and whole brain SWM disruption in patients who developed epilepsy during childhood. On the other hand, in patients with adult-onset TLE, co-occurring cortical and SWM alterations were observed in the medial temporal lobe ipsilateral to the seizure focus.SignificanceOur results suggest that although cortical, hippocampal and WM alterations appear spatially discordant at the group level, the relationship among these features depends on the age at which seizures begin. Whereas neurodevelopmental aspects of TLE may result in co-occurring WM and hippocampal degeneration near the epileptogenic zone, the onset of seizures in adulthood may set off a cascade of SWM microstructural loss and cortical atrophy of a neurodegenerative nature.

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

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

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