Dataset Information

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

ABSTRACT:

Objectives

Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments.

Methods

We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves.

Results

In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions.

Conclusions

This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

SUBMITTER: Chen J

PROVIDER: S-EPMC10942350 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Chen Judy J Ngo Alexander A Rodríguez-Cruces Raúl R Royer Jessica J Caligiuri Maria Eugenia ME Gambardella Antonio A Concha Luis L Keller Simon S SS Cendes Fernando F Yasuda Clarissa L CL Alvim Marina K M MKM Bonilha Leonardo L Gleichgerrcht Ezequiel E Focke Niels K NK Kreilkamp Barbara B Domin Martin M von Podewils Felix F Langner Soenke S Rummel Christian C Wiest Roland R Martin Pascal P Kotikalapudi Raviteja R Bender Benjamin B O'Brien Terence J TJ Sinclair Benjamin B Vivash Lucy L Kwan Patrick P Desmond Patricia M PM Lui Elaine E Duma Gian Marco GM Bonanni Paolo P Ballerini Alice A Vaudano Anna Elisabetta AE Meletti Stefano S Tondelli Manuela M Alhusaini Saud S Doherty Colin P CP Cavalleri Gianpiero L GL Delanty Norman N Kälviäinen Reetta R Jackson Graeme D GD Kowalczyk Magdalena M Mascalchi Mario M Semmelroch Mira M Thomas Rhys H RH Soltanian-Zadeh Hamid H Davoodi-Bojd Esmaeil E Zhang Junsong J Lenge Matteo M Guerrini Renzo R Bartolini Emanuele E Hamandi Khalid K Foley Sonya S Rüber Theodor T Bauer Tobias T Weber Bernd B Caldairou Benoit B Depondt Chantal C Absil Julie J Carr Sarah J A SJA Abela Eugenio E Richardson Mark P MP Devinsky Orrin O Pardoe Heath H Severino Mariasavina M Striano Pasquale P Tortora Domenico D Kaestner Erik E Hatton Sean N SN Arienzo Donatello D Vos Sjoerd B SB Ryten Mina M Taylor Peter N PN Duncan John S JS Whelan Christopher D CD Galovic Marian M Winston Gavin P GP Thomopoulos Sophia I SI Thompson Paul M PM Sisodiya Sanjay M SM Labate Angelo A McDonald Carrie R CR Caciagli Lorenzo L Bernasconi Neda N Bernasconi Andrea A Larivière Sara S Schrader Dewi D Bernhardt Boris C BC

bioRxiv : the preprint server for biology 20240306

<h4>Objectives</h4>Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covaria ...[more]

PMID: 38496668

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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.

Project description:The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.

Project description:It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called "age differentiation" additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences within and between brain and cognition across the adult life span (18-88 years) in a large (N > 646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of gray matter volume (from T1- and T2-weighted MRI) and white matter organization (fractional anisotropy from diffusion-weighted MRI), we found evidence for the differentiation of gray and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation among fluid intelligence, language, and memory, suggesting a relatively stable covariance pattern among cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with the reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age.SIGNIFICANCE STATEMENT The theory of age differentiation posits age-related changes in the relationships among cognitive domains, either weakening (differentiation) or strengthening (dedifferentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult life span sample, we found age-related reductions in the covariance among both brain measures (neural differentiation), but no covariance change among cognitive factors of fluid intelligence, language, and memory. We also observed evidence of uncoupling (differentiation) between a white matter factor and cognitive factors in older age, most strongly for memory. Together, our findings support age-related differentiation as a complex, multifaceted pattern that differs for brain and cognition, and discuss several mechanisms that might explain the changing relationship between brain and cognition.

Project description:ObjectiveFurther studies are needed to improve the understanding of the pathological process underlying cognitive impairments. The purpose of this study is to investigate the global and topographic changes of white matter integrity and cortical structure related to cognitive impairments in a community-based population.MethodsA cross-sectional analysis was performed based on 995 subjects (aged 56.8 ± 9.1 years, 34.8% males) from the Shunyi study, a community-dwelling cohort. Cognitive status was accessed by a series of neurocognitive tests including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), category Verbal Fluency Test (VFT), Digit Span Test (DST), and Trail Making Tests A and B (TMT-A and TMT-B). Structural and diffusional MRI data were acquired. White matter integrity was assessed using fractional anisotropy (FA), mean diffusivity (MD), and peak width of skeletonized mean diffusivity (PSMD). Cortical surface area, thickness, and volume were measured using Freesurfer. Probabilistic tractography was further conducted to track the white matter fibers connecting to the cortical regions related to cognition. General linear models were used to investigate the association between brain structure and cognition.ResultsGlobal mean FA and MD were significantly associated with performances in VFT (FA, β 0.119, p < 0.001; MD, β -0.128, p < 0.001). Global cortical surface area, thickness, and volume were not related to cognitive scores. In tract-based spatial statistics analysis, disruptive white matter integrity was related to cognition impairment, mainly in visuomotor processing speed, semantic memory, and executive function (TMT-A and VFT), rather than verbal short-term memory and working memory (DST). In the whole brain vertex-wise analysis, surface area in the left orbitofrontal cortex, right posterior-dorsal part of the cingulate gyrus, and left central sulcus were positively associated with MMSE and MoCA scores, and the association were independent of the connecting white matter tract.ConclusionDisrupted white matter integrity and regional cortical surface area were related to cognition in community-dwelling populations. The associations of cortical surface area and cognition were independent of the connecting white matter tract.

Dataset Information

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Objectives

Methods

Results

Conclusions

Publications

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Similar Datasets

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