Hippocampal pathology in amyotrophic lateral sclerosis: selective vulnerability of subfields and their associated projections

Christidi, Foteini; Karavasilis, Efstratios; Rentzos, Michael; Velonakis, Georgios; Zouvelou, Vasiliki; Xirou, Sophia; Argyropoulos, G; Papatriantafyllou, Ioannis; Pantolewn, Varvara; Ferentinos, Panagiotis; Kelekis, Nikolaos; Seimenis, Ioannis; Evdokimidis, Ioannis; Bede, Peter

doi:10.1016/j.neurobiolaging.2019.07.019

Cited by 69 publications

(72 citation statements)

References 82 publications

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“…10,14 Since the nucleus accumbens controls impulsivity and aggression, pathological changes in this structure may be related to the behavioral changes in ALS patients. 17 Several previous studies 14,15,36 have found reduced hippocampal volumes, whereas we found no significant differences in the volume of the hippocampus. This discrepancy might be related to our study only enrolling patients with relatively early-stage ALS who did not have obvious cognitive impairment.…”

Section: Discussioncontrasting

confidence: 59%

Shape Analysis of the Subcortical Nuclei in Amyotrophic Lateral Sclerosis without Cognitive Impairment

et al. 2020

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Background and Purpose Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the pyramidal motor system. However, recent studies have suggested that degeneration of the extramotor system plays a role in the disability experienced by patients with ALS. We investigated the local shape changes and mean volumes of the subcortical nuclei in sporadic ALS patients with preserved cognition. Methods The participants comprised 32 patients with ALS and 43 age-and sex-matched healthy controls. Three-dimensional T1-weighted structural images were acquired. Surfacebased vertex analysis was performed with fully automated segmentation of both amygdalae, hippocampi, caudate nuclei, nuclei accumbens, putamina, pallida, and thalami, and the brainstem. The scalar distances from the mean surfaces of the individual subcortical nuclei were compared between groups, and correlations of the local shape distances with initial Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALS-FRS-R) scores and the delta FRS-R and with the disease duration were analyzed. Results ALS patients showed regional shape contractions on the lateral surfaces of both pallida, the lateroposterior surface of the right putamen, and the anterior basal surface of the right accumbens. Delta FRS-R scores were negatively correlated with local shape distances in the right hippocampus and the putamina. However, the initial ALS-FRS-R score and disease duration were not correlated with local shape distances. Conclusions Subcortical gray-matter structures are involved in the neurodegenerative process of ALS before cognitive impairment becomes evident.

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Section: Discussioncontrasting

confidence: 59%

Shape Analysis of the Subcortical Nuclei in Amyotrophic Lateral Sclerosis without Cognitive Impairment

et al. 2020

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“… 42 Other studies indicated that interconnected gray matter regions become gradually affected instead of being subject to contiguous spread. 10 , 43 Future research could, therefore, examine differences between the Braak stages and observed disease spread in patients. As patients with early diagnosis may have a more aggressive disease course, 44 we investigated whether the observed effects reflect a more progressive disease course, but no clear relation between neuroimaging effects and disease progression was found in patients with short or long disease duration.…”

Section: Discussionmentioning

confidence: 99%

Multimodal longitudinal study of structural brain involvement in amyotrophic lateral sclerosis

et al. 2020

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ObjectiveTo understand the progressive nature of amyotrophic lateral sclerosis (ALS) by investigating differential brain patterns of gray and white matter involvement in clinically or genetically defined subgroups of patients using cross-sectional, longitudinal, and multimodal MRI.MethodsWe assessed cortical thickness, subcortical volumes, and white matter connectivity from T1-weighted and diffusion-weighted MRI in 292 patients with ALS (follow-up: n = 150) and 156 controls (follow-up: n = 72). Linear mixed-effects models were used to assess changes in structural brain measurements over time in patients compared to controls.ResultsPatients with a C9orf72 mutation (n = 24) showed widespread gray and white matter involvement at baseline, and extensive loss of white matter integrity in the connectome over time. In C9orf72-negative patients, we detected cortical thinning of motor and frontotemporal regions, and loss of white matter integrity of connections linked to the motor cortex. Patients with spinal onset displayed widespread white matter involvement at baseline and gray matter atrophy over time, whereas patients with bulbar onset started out with prominent gray matter involvement. Patients with unaffected cognition or behavior displayed predominantly motor system involvement, while widespread cerebral changes, including frontotemporal regions with progressive white matter involvement over time, were associated with impaired behavior or cognition. Progressive loss of gray and white matter integrity typically occurred in patients with shorter disease durations (<13 months), independent of progression rate.ConclusionsHeterogeneity of phenotype and C9orf72 genotype relates to distinct patterns of cerebral degeneration. We demonstrate that imaging studies have the potential to monitor disease progression and early intervention may be required to limit cerebral degeneration.

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“…The HATA was connected with the amygdala closely, and compared with the healthy group, the volumes of HATA were reduced in the MCI group [ 2 , 38 ]. In another study, obvious changes in fimbria were observed in AD [ 39 ]. The change of parasubiculum affected the medial temporal memory system and dementia, and AD patients had more cellular neurofibrillary tangles in parasubiculum [ 40 , 41 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Hippocampal Subregion and Gene Detection in Alzheimer’s Disease Based on Genetic Clustering Random Forest

Jin

Liu

Cao

et al. 2021

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The distinguishable subregions that compose the hippocampus are differently involved in functions associated with Alzheimer’s disease (AD). Thus, the identification of hippocampal subregions and genes that classify AD and healthy control (HC) groups with high accuracy is meaningful. In this study, by jointly analyzing the multimodal data, we propose a novel method to construct fusion features and a classification method based on the random forest for identifying the important features. Specifically, we construct the fusion features using the gene sequence and subregions correlation to reduce the diversity in same group. Moreover, samples and features are selected randomly to construct a random forest, and genetic algorithm and clustering evolutionary are used to amplify the difference in initial decision trees and evolve the trees. The features in resulting decision trees that reach the peak classification are the important “subregion gene pairs”. The findings verify that our method outperforms well in classification performance and generalization. Particularly, we identified some significant subregions and genes, such as hippocampus amygdala transition area (HATA), fimbria, parasubiculum and genes included RYR3 and PRKCE. These discoveries provide some new candidate genes for AD and demonstrate the contribution of hippocampal subregions and genes to AD.

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Hippocampal pathology in amyotrophic lateral sclerosis: selective vulnerability of subfields and their associated projections

Cited by 69 publications

References 82 publications

Shape Analysis of the Subcortical Nuclei in Amyotrophic Lateral Sclerosis without Cognitive Impairment

Shape Analysis of the Subcortical Nuclei in Amyotrophic Lateral Sclerosis without Cognitive Impairment

Multimodal longitudinal study of structural brain involvement in amyotrophic lateral sclerosis

Hippocampal Subregion and Gene Detection in Alzheimer’s Disease Based on Genetic Clustering Random Forest

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