Glutamatergic response to a low load working memory paradigm in the left dorsolateral prefrontal cortex in patients with mild cognitive impairment: a functional magnetic resonance spectroscopy study

Vijayakumari, Anupa A.; Menon, Ramshekhar; Arun, T.; Mohanan, Nandini; Kesavadas, Chandrasekharan

doi:10.1007/s11682-019-00122-7

Cited by 16 publications

(15 citation statements)

References 36 publications

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“…Another functional magnetic resonance imaging (fMRI) study included 15 patients with amnestic MCI and 22 age-, sex-, and education-matched healthy controls. A significant increase was observed in glutamate during a working memory task (both zero back and one back) in healthy controls, but no significant changes were detected in patients with MCI [108]. Mangas et al observed that the d-glutamate level was higher in the cell body of the mouse brain regions, such as the ventral part of the mesencephalic central grey, the dorsal raphe nucleus, above the posterior commissure, the superior colliculus, and the subparafascicular thalamic nucleus [19].…”

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

confidence: 81%

“…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

121

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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: 81%

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

121

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“…One that included eight patients with MCI, nine patients with AD and 16 healthy controls found that reduced hippocampal glutamate in MCI and AD was associated with episodic memory performance (Wong et al, 2020). The other study performed fMRI in 15 patients with amnestic MCI and 22 age-, sex- and education-matched healthy controls, and observed a significant increase in glutamate during a working memory task (both 0 back and 1 back) in healthy controls, but no significant changes were detected in patients with MCI (Vijayakumari et al, 2019). In an animal study, the d -glutamate level was higher in the cell body of mouse brain regions such as the ventral part of the mesencephalic central grey, the dorsal raphe nucleus, the superior colliculus, the subparafascicular thalamic nucleus and above the posterior commissure (Mangas et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Plasma d-glutamate levels for detecting mild cognitive impairment and Alzheimer’s disease: Machine learning approaches

et al. 2021

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Background: d-glutamate, which is involved in N-methyl-d-aspartate receptor modulation, may be associated with cognitive ageing. Aims: This study aimed to use peripheral plasma d-glutamate levels to differentiate patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) from healthy individuals and to evaluate its prediction ability using machine learning. Methods: Overall, 31 healthy controls, 21 patients with MCI and 133 patients with AD were recruited. Serum d-glutamate levels were measured using high-performance liquid chromatography (HPLC). Cognitive deficit severity was assessed using the Clinical Dementia Rating scale and the Mini-Mental Status Examination (MMSE). We employed four machine learning algorithms (support vector machine, logistic regression, random forest and naïve Bayes) to build an optimal predictive model to distinguish patients with MCI or AD from healthy controls. Results: The MCI and AD groups had lower plasma d-glutamate levels (1097.79 ± 283.99 and 785.10 ± 720.06 ng/mL, respectively) compared to healthy controls (1620.08 ± 548.80 ng/mL). The naïve Bayes model and random forest model appeared to be the best models for determining MCI and AD susceptibility, respectively (area under the receiver operating characteristic curve: 0.8207 and 0.7900; sensitivity: 0.8438 and 0.6997; and specificity: 0.8158 and 0.9188, respectively). The total MMSE score was positively correlated with d-glutamate levels ( r = 0.368, p < 0.001). Multivariate regression analysis indicated that d-glutamate levels were significantly associated with the total MMSE score ( B = 0.003, 95% confidence interval 0.002–0.005, p < 0.001). Conclusions: Peripheral plasma d-glutamate levels were associated with cognitive impairment and may therefore be a suitable peripheral biomarker for detecting MCI and AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing MCI and AD in outpatient clinics.

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“…DLPFC region is well known for its role in verbal and nonverbal memory retrieval along with cognitive process [18][19][20][21][22][23]. It has been suggested that stimulation of left DLP-FC improves cognition and memory simultaneously [24].…”

Section: Discussionmentioning

confidence: 99%