Reduced Hippocampal Glutamate and Posterior Cingulate N-Acetyl Aspartate in Mild Cognitive Impairment and Alzheimer’s Disease Is Associated with Episodic Memory Performance and White Matter Integrity in the Cingulum: A Pilot Study

Wong, Dickson; Atiya, Samir; Fogarty, Jennifer; Montero‐Odasso, Manuel; Pasternak, Stephen; Brymer, Chris; Borrie, Michael; Bartha, Robert

doi:10.3233/jad-190773

Cited by 41 publications

(31 citation statements)

References 113 publications

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“…These observations lead to the question: how is the lower peripheral d-glutamate level related to cognitive impairment? A pilot study enrolled eight individuals with MCI, nine individuals with AD, and 16 healthy elderly controls, finding that reduced hippocampal glutamate in MCI and AD was associated with episodic memory performance [107]. Another functional magnetic resonance imaging (fMRI) study included 15 patients with amnestic MCI and 22 age-, sex-, and education-matched healthy controls.…”

Section: Potential Role Of D-glutamate In Alzheimer's Diseasementioning

confidence: 99%

“…Moreover, previous studies have found decreased glutamate in the brain is associated with impaired cognitive functions. A study of eight individuals with MCI, nine individuals with AD, and 16 healthy elderly controls found that reduced hippocampal glutamate in MCI and AD was associated with episodic memory performance [107], while another functional magnetic resonance imaging (fMRI) study noted reduced glutamate change in brain during a working memory task in patients with MCI [108].…”

Section: Potential Role Of D-glutamate In Brain-gut-microbiota Axismentioning

confidence: 99%

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d-glutamate and Gut Microbiota in Alzheimer’s Disease

Chang

Lin

Lane

2020

IJMS

119

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Background: An increasing number of studies have shown that the brain–gut–microbiota axis may significantly contribute to Alzheimer’s disease (AD) pathogenesis. Moreover, impaired memory and learning involve the dysfunction neurotransmission of glutamate, the agonist of the N-methyl-d-aspartate receptor and a major excitatory neurotransmitter in the brain. This systematic review aimed to summarize the current cutting-edge research on the gut microbiota and glutamate alterations associated with dementia. Methods: PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews were reviewed for all studies on glutamate and gut microbiota in dementia published up until Feb 2020. Results: Several pilot studies have reported alterations of gut microbiota and metabolites in AD patients and other forms of dementia. Gut microbiota including Bacteroides vulgatus and Campylobacter jejuni affect glutamate metabolism and decrease the glutamate metabolite 2-keto-glutaramic acid. Meanwhile, gut bacteria with glutamate racemase including Corynebacterium glutamicum, Brevibacterium lactofermentum, and Brevibacterium avium can convert l-glutamate to d-glutamate. N-methyl-d-aspartate glutamate receptor (NMDAR)-enhancing agents have been found to potentially improve cognition in AD or Parkinson’s disease patients. These findings suggest that d-glutamate (d-form glutamate) metabolized by the gut bacteria may influence the glutamate NMDAR and cognitive function in dementia patients. Conclusions: Gut microbiota and glutamate are potential novel interventions to be developed for dementia. Exploring comprehensive cognitive functions in animal and human trials with glutamate-related NMDAR enhancers are warranted to examine d-glutamate signaling efficacy in gut microbiota in patients with AD and other neurodegenerative dementias.

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Section: Potential Role Of D-glutamate In Alzheimer's Diseasementioning

confidence: 99%

Section: Potential Role Of D-glutamate In Brain-gut-microbiota Axismentioning

confidence: 99%

d-glutamate and Gut Microbiota in Alzheimer’s Disease

Chang

Lin

Lane

2020

IJMS

119

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“…Early MRS studies show abnormal concentrations of N-acetylaspartate (NAA), creatine, and choline are associated with the status of memory and cognition impairment and have a promise for assessing cognitive status, evaluating response to medicine, and monitoring progression during treatment [76] , [77] , [78] . In recent years, with advances in the technical development of MR hardware and pulse sequences, the roles of glutamate, the excitatory neurotransmitter, and GABA, the inhibitory neurotransmitter, in MCI patients became the main focus [79] , [80] , [81] . For example, with ultra-high field 7 Tesla MR scanner, abnormal concentrations of GABA, glutamate, NAA, glutathione, and myo-inositol (mI) in different brain regions were detected [82] .…”

Section: Multimodal Imaging Data Fusion: Diseasesmentioning

confidence: 99%

Advances in multimodal data fusion in neuroimaging: Overview, challenges, and novel orientation

et al. 2020

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Highlights We analysed over 450 references from all well-famed databases. We provided a comprehensive survey on multimodal data fusion in neuroimaging. This review encompassed current challenges & applications, strengths &limitations. Fundamental fusion rules, and fusion quality assessment methods were reviewed. Atlas-based fusion segmentation, quantification, & applications were reviewed.

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“…In recent years, D-glutamate has become a molecule of interest for its protective effects against the behavioral symptoms of Alzheimer’s Disease [ 33 , 40 , 41 ]. Specifically, Alzheimer’s Disease is marked by a decrease in circulating D-glutamate as well as decreased D-glutamate in the hippocampus.…”

Section: Nmda Receptor Agonists or Co-agonistsmentioning

confidence: 99%

“…Specifically, Alzheimer’s Disease is marked by a decrease in circulating D-glutamate as well as decreased D-glutamate in the hippocampus. It has been suggested that the loss of D-glutamate leads to reduced NMAD receptor activation and hence a worsening of symptoms [ 14 , 33 , 40 , 41 ]. D-Glutamate is thought to be absorbed from food as well as produced in the gut by bacteria, and it has been suggested that gut bacteria derived D-glutamate could be a novel therapeutic to slow the progression of Alzheimer’s Disease [ 14 ].…”

Section: Nmda Receptor Agonists or Co-agonistsmentioning

confidence: 99%

Advances in D-Amino Acids in Neurological Research

Seckler

Lewis

2020

IJMS

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D-amino acids have been known to exist in the human brain for nearly 40 years, and they continue to be a field of active study to today. This review article aims to give a concise overview of the recent advances in D-amino acid research as they relate to the brain and neurological disorders. This work has largely been focused on modulation of the N-methyl-D-aspartate (NMDA) receptor and its relationship to Alzheimer’s disease and Schizophrenia, but there has been a wealth of novel research which has elucidated a novel role for several D-amino acids in altering brain chemistry in a neuroprotective manner. D-amino acids which have no currently known activity in the brain but which have active derivatives will also be reviewed.

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Reduced Hippocampal Glutamate and Posterior Cingulate N-Acetyl Aspartate in Mild Cognitive Impairment and Alzheimer’s Disease Is Associated with Episodic Memory Performance and White Matter Integrity in the Cingulum: A Pilot Study

Cited by 41 publications

References 113 publications

d-glutamate and Gut Microbiota in Alzheimer’s Disease

d-glutamate and Gut Microbiota in Alzheimer’s Disease

Advances in multimodal data fusion in neuroimaging: Overview, challenges, and novel orientation

Advances in D-Amino Acids in Neurological Research

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