Hippocampal dysfunction is associated with memory impairment in multiple sclerosis: A volumetric and functional connectivity study

Background: Previous studies have suggested a relationship between neuroanatomical and neurofunctional hippocampal alterations and episodic memory impairments in multiple sclerosis (MS) patients. Objective: We examined hippocampus volume and functional connectivity (FC) changes in MS patients with different episodic memory capabilities. Methods: Hippocampal subfield volume and FC changes were compared in two subgroups of MS patients with and without episodic memory impairment (multiple sclerosis impaired (MSi) and multiple sclerosis preserved (MSp), respectively) and healthy controls (HC). A discriminant function (DF) analysis was used to identify which of these neuroanatomical and neurofunctional parameters were the most relevant components of the mnemonic profiles of HC, MSp, and MSi. Results: MSi showed reduced volume in several hippocampal subfields compared to MSp and HC. Ordinal gradation (MSi > MSp > HC) was also observed for FC between the posterior hippocampus and several cortical areas. DF-based analyses revealed that reduced right fimbria volume and enhanced FC at the right posterior hippocampus were the main neural signatures of the episodic memory impairments observed in the MSi group. Conclusion: Before any sign of episodic memory alterations (MSp), FC increased on several pathways that connect the hippocampus with cortical areas. These changes further increased when the several hippocampal volumes reduced and memory deficits appeared (MSi).

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Does Fatigue Complaint Reflect Memory Impairment in Multiple Sclerosis?

Multiple Sclerosis International ◽

10.1155/2014/692468 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Caroline Jougleux-Vie ◽

Emeline Duhin ◽

Valerie Deken ◽

Olivier Outteryck ◽

Patrick Vermersch ◽

...

Keyword(s):

Multiple Sclerosis ◽

Episodic Memory ◽

Memory Impairment ◽

Subjective Assessment ◽

Depression Score ◽

Confounding Factors ◽

Memory Complaint ◽

Subjective Fatigue ◽

With Memory ◽

Verbal Episodic Memory

Background and Purpose. Fatigue and memory impairment are common symptoms in multiple sclerosis (MS) and both may interact with cognition. This can contribute to making a complaint misrepresentative of the objective disorder. We sought to determine whether fatigue complaint in MS reflects memory impairment and investigated whether patients’ subjective fatigue is associated with memory complaint.Methods. Fifty MS patients complaining of fatigue underwent subjective assessment of fatigue and memory complaint measured using self-assessment scales. Cognitive functions were assessed using a battery of neuropsychological tests, including a test of verbal episodic memory, the selective reminding test (SRT). Correlations were studied between subjective fatigue, memory complaint, and performance in verbal episodic memory.Results. Depression score, psychotropic and/or antiepileptic drug use, Expanded Disability Status Scale (EDSS) score, and MS form were confounding factors. After adjusting for these confounding factors, neither fatigue complaint nor memory complaint was correlated with SRT performance. Subjective fatigue was significantly associated with memory complaint.Conclusion. Although complaint of fatigue in MS was correlated with memory complaint, subjective fatigue was not the expression of memory impairment.

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Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

Brain ◽

10.1093/brain/awab114 ◽

2021 ◽

Author(s):

David Berron ◽

Jacob W Vogel ◽

Philip S Insel ◽

Joana B Pereira ◽

Long Xie ◽

...

Keyword(s):

Functional Connectivity ◽

Entorhinal Cortex ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Memory Impairment ◽

Memory Performance ◽

Hippocampal Atrophy ◽

Tau Pathology ◽

Β Amyloid ◽

With Memory

Abstract In Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior-medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance. We included 215 β-amyloid negative cognitively unimpaired, 81 β-amyloid positive cognitively unimpaired and 87 β-amyloid positive individuals with mild cognitive impairment, who each underwent [18]F-RO948 tau and [18]F-flutemetamol amyloid PET imaging, structural T1-MRI and memory assessments as part of the Swedish BioFINDER-2 study. First, event-based modelling revealed that the entorhinal cortex and area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions. Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau-related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior-medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy. In summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease-stage specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe-cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.

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A CSF biomarker of intrathecal B cells activation correlates with memory impairment in multiple sclerosis

Journal of the Neurological Sciences ◽

10.1016/j.jns.2021.117772 ◽

2021 ◽

Vol 429 ◽

pp. 117772

Author(s):

Lorenzo Gaetani ◽

Giovanni Brachelente ◽

Nicola Salvadori ◽

Elena Chipi ◽

Elena Di Sabatino ◽

...

Keyword(s):

Multiple Sclerosis ◽

B Cells ◽

Memory Impairment ◽

Csf Biomarker ◽

With Memory

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Delayed recall memory impairment in patients with Parkinson's disease

Dementia & Neuropsychologia ◽

10.1590/s1980-5764-2016dn1003006 ◽

2016 ◽

Vol 10 (3) ◽

pp. 204-209 ◽

Cited By ~ 1

Author(s):

Arthur Oscar Schelp ◽

Cristiane Lara Mendes-Chiloff ◽

Vanessa Cristina Paduan ◽

José Eduardo Corrente ◽

Fabrício Diniz de Lima ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Episodic Memory ◽

Memory Impairment ◽

Rating Scale ◽

Demographic Variables ◽

Delayed Recall ◽

Recall Memory ◽

Significant Difference ◽

With Memory

ABSTRACT Age is one of the risk factors for dementia in patients with Parkinson's disease (PDD). Distinct cognitive syndromes of Parkinson's disease (PD) have been identified in previous studies. Questions about the role of such cognitive disorders in PD outcomes, especially memory dysfunction, in patients with PD remain unanswered. Objective: To establish possible correlations between delayed recall memory (episodic memory), age, and other demographic variables in patients with PD. Methods: A two-stage protocol was applied. Patients with delayed recall memory compromise, selected based on a brief battery of tests (BBRC-Edu), were classified as dementia cases and submitted to the Mattis Dementia Rating Scale (MDRS). Data from patients with memory disturbances were compared against individuals without episodic memory impairment, and correlated with age and demographic variables. Results: Except for identification and naming, all subtests in the screening battery showed a significant difference (p≤0.0001) between the memory-compromised group (case) and the group without memory impairment (no case). The results also correlated negatively with age (p≤0.0001) and positively with level of education (p=0.0874) in patients with PD. Conclusion: The analysis showed a significant relationship between age and dementia characterized by impaired episodic memory. The findings support reports of a wide spectrum of neuropsychological performance impairment in PD with age, particularly dementia associated with memory deterioration. No correlations between disease duration and cognitive dysfunction were evident.

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Effects of amnesia on processing in the hippocampus and default mode network during a naturalistic memory task: a case study

10.31234/osf.io/e9n8c ◽

2018 ◽

Author(s):

Christiane Oedekoven ◽

James L. Keidel ◽

Stuart Anderson ◽

Angus Nisbet ◽

Chris Bird

Keyword(s):

Functional Connectivity ◽

Episodic Memory ◽

Memory Performance ◽

Memory Task ◽

Structural Mri ◽

Brain Regions ◽

Left Hippocampus ◽

Cortical Regions ◽

The Right ◽

Encoding And Retrieval

Despite their severely impaired episodic memory, individuals with amnesia are able to comprehend ongoing events. Online representations of a current event are thought to be supported by a network of regions centred on the posterior midline cortex (PMC). By contrast, episodic memory is widely believed to be supported by interactions between the hippocampus and these cortical regions. In this MRI study, we investigated the encoding and retrieval of lifelike events (video clips) in a patient with severe amnesia likely resulting from a stroke to the right thalamus, and a group of 20 age-matched controls. Structural MRI revealed grey matter reductions in left hippocampus and left thalamus in comparison to controls. We first characterised the regions activated in the controls while they watched and retrieved the videos. There were no differences in activation between the patient and controls in any of the regions. We then identified a widespread network of brain regions, including the hippocampus, that were functionally connected with the PMC in controls. However, in the patient there was a specific reduction in functional connectivity between the PMC and a region of left hippocampus when both watching and attempting to retrieve the videos. A follow up analysis revealed that in controls the functional connectivity between these regions when watching the videos was correlated with memory performance. Taken together, these findings support the view that the interactions between the PMC and the hippocampus enable the encoding and retrieval of multimodal representations of the contents of an event.

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Calbindin-1 Expression in the Hippocampus following Neonatal Hypoxia-Ischemia and Therapeutic Hypothermia and Deficits in Spatial Memory

Developmental Neuroscience ◽

10.1159/000497056 ◽

2018 ◽

Vol 40 (5-6) ◽

pp. 508-522 ◽

Cited By ~ 2

Author(s):

Janasha Goffigan-Holmes ◽

Dafne Sanabria ◽

Johana Diaz ◽

Debra Flock ◽

Raul Chavez-Valdez

Keyword(s):

Therapeutic Hypothermia ◽

Neurodegenerative Disorders ◽

Memory Impairment ◽

Memory Deficits ◽

Nissl Staining ◽

Memory Impairments ◽

Neonatal Hypoxia ◽

Y Maze ◽

Hypoxia Ischemia ◽

With Memory

Hippocampal injury following neonatal hypoxia-ischemia (HI) leads to memory impairments despite therapeutic hypothermia (TH). In the hippocampus, the expression of calbindin-1 (Calb1), a Ca2+-buffering protein, increases during postnatal development and decreases with aging and neurodegenerative disorders. Since persistent Ca2+ dysregulation after HI may lead to ongoing injury, persistent changes in hippocampal expression of Calb1 may contribute to memory impairments after neonatal HI. We hypothesized that, despite TH, neonatal HI persistently decreases Calb1 expression in the hippocampus, a change associated with memory deficits in the mouse. We induced cerebral HI in C57BL6 mice at postnatal day 10 (P10) with right carotid ligation and 45 min of hypoxia (FiO2 = 0.08), followed by normothermia (36°C, NT) or TH (31°C) for 4 h with anesthesia-shams as controls. Nissl staining and glial fibrillary acidic protein (GFAP) immunohistochemistry (IHC) were used to grade brain injury and astrogliosis at P11, P18, and P40 prior to the assessment of Calb1 expression by IHC. The subset of mice followed to P40 also performed a memory behavior task (Y-maze) at P22–P26. Nonparametric statistics stratified by sex were applied. In both anterior and posterior coronal brain sections, hippocampal Calb1 expression doubled between P11 and P40 due to an increase in the cornus ammonis (CA) field (Kruskal-Wallis [KW] p < 0.001) and not the dentate gyrus (DG). Neonatal HI produced delayed (P18) and late (P40) deficits in the expression of Calb1 exclusively in the CA field (KW p = 0.02) in posterior brain sections. TH did not attenuate Calb1 deficits after HI. Thirty days after HI injury (at P40), GFAP scores in the hippocampus (p < 0.001, r = –0.47) and CA field (p < 0.001, r = –0.39) of posterior brain sections inversely correlated with their respective Calb1 expression. Both sexes demonstrated deficits in Y-maze testing, including approximately 40% lower spontaneous alterations performance and twice as much total impairment compared to sham mice (KW p < 0.001), but it was only in females that these deficits correlated with the Calb1 expression in the hippocampal CA field (p < 0.05) of the posterior sections. Hippocampal atrophy after neonatal HI also correlated with worse deficits in Y-maze testing, but it did not predict Calb1 deficits. Neonatal HI produces a long-lasting Calb1 deficit in the hippocampal CA field during development, which is not mitigated by TH. Late Calb1 deficit after HI may be the result of persistent astrogliosis and can lead to memory impairment, particularly in female mice.

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Enhanced resting-state functional connectivity between core memory-task activation peaks is associated with memory impairment in MCI

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2016.04.018 ◽

2016 ◽

Vol 45 ◽

pp. 43-49 ◽

Cited By ~ 18

Author(s):

Yifei Zhang ◽

Lee Simon-Vermot ◽

Miguel Á. Araque Caballero ◽

Benno Gesierich ◽

Alexander N.W. Taylor ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Memory Impairment ◽

Memory Task ◽

Core Memory ◽

Resting State Functional Connectivity ◽

With Memory ◽

Task Activation

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Effect of Metformin on Doxorubicin-Induced Memory Dysfunction

Brain Sciences ◽

10.3390/brainsci10030152 ◽

2020 ◽

Vol 10 (3) ◽

pp. 152

Author(s):

Ibrahim Alharbi ◽

Hindi Alharbi ◽

Yasser Almogbel ◽

Abdullah Alalwan ◽

Ahmad Alhowail

Keyword(s):

Cognitive Dysfunction ◽

Memory Impairment ◽

Elevated Plus Maze ◽

Male Rats ◽

Memory Impairments ◽

Glucose Levels ◽

Y Maze ◽

Altered Glucose ◽

Plus Maze ◽

With Memory

Doxorubicin (DOX) is widely used to treat many types of cancer; however, it is associated with chemotherapy-related complications such as cognitive dysfunction, known as chemobrain. Chemobrain affects up to 75% of cancer survivors, and there are currently no available therapeutic options. This study aims to examine whether metformin (MET) can protect against the neurotoxicity caused by DOX treatment. Forty male rats were divided into four groups (10 rats/group): control, DOX, DOX + MET, and MET. Rats treated with DOX received five doses of 4 mg/kg DOX weekly (cumulative dose: 20 mg/kg). For the DOX-MET and MET groups, MET (3 mg/mL) was dissolved in drinking water. Behavioral and glucose tests were performed one day after treatment was completed. We found DOX (4 mg/kg/week, 5 weeks) caused learning and memory impairment in the Y-maze, novel object recognition, and elevated plus maze behavioral tests. MET did not rescue these DOX-induced memory impairments. Neither DOX nor MET nor MET + DOX altered glucose levels following the treatment. In summary, DOX treatment is associated with memory impairment in rats, but MET does not rescue this cognitive dysfunction.

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