Alterations of Brain Metabolites in Adults With HIV: A Systematic Meta-analysis of Magnetic Resonance Spectroscopy Studies

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012394
Author(s):  
Sophia Dahmani ◽  
Nicholas Kaliss ◽  
John W. VanMeter ◽  
David J Moore ◽  
Ronald J. Ellis ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Basal Ganglia ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Meta Analysis ◽  
Brain Regions ◽  
Resonance Spectroscopy ◽  
Signal Pathways ◽  
Brain Metabolites

Objective.A meta-analysis of proton magnetic resonance spectroscopy (MRS) studies to investigate alterations in brain metabolites in people with HIV (PWH), as well as their relationship with combination antiretroviral therapy (cART) and cognitive impairment.Methods.The PubMed database was searched for studies published from 1997 to 2020. Twenty-seven studies were identified, which included 1255 PWH and 633 controls. Four metabolites (N-acetyl aspartate (NAA), myo-Inositol (mI), choline (Cho), and glutamatergic metabolites (Glx) from five brain regions (basal ganglia (BG), frontal gray and white matter (FGM, FWM), and parietal gray and white matter (PGM, PWM)) were pooled separately using random-effects meta-analysis.Results.During early HIV infection, metabolite alterations were largely limited to the BG, including Cho elevation, a marker of inflammation. cART led to global mI and Cho normalization (i.e., less elevations), but improvement in NAA was negligible. In chronic PWH on cART, there were consistent NAA reductions across brain regions, along with Cho and mI elevations in the FWM and BG, and Glx elevations in the FWM. Cognitive impairment was associated with NAA reduction and to a lesser degree, mI elevation.Conclusions.The basal ganglia is the primary region affected during early infection. cART is successful in partially controlling neuroinflammation (global mI and Cho normalization). However, neuronal dysfunction (NAA reductions) and neuroinflammation (mI and Cho elevations) persist and contribute to cognitive impairment in chronic PWH. Novel compounds targeting NAA signal pathways, along with better neuroinflammation control, may help to reduce cognitive impairment in PWH.

Longitudinal Functional Magnetic Resonance Spectroscopy Study in Subjects with Mild Cognitive Impairment and Alzheimer’s Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Soo-Hyun Cho ◽  
Hak Young Rhee ◽  
Janghoon Oh ◽  
Jin San Lee ◽  
Soonchan Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Resonance Spectroscopy ◽  
Brain Metabolites ◽  
Functional Magnetic Resonance ◽  
Longitudinal Changes ◽  
Functional Magnetic Resonance Spectroscopy

Background: Longitudinal changes of brain metabolites during a functional stimulation are unknown in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) subjects. Objective: This study was to evaluate the longitudinal changes of brain metabolites using proton magnetic resonance spectroscopy (1H MRS) in response to treatment during a memory task in the subjects of cognitive normal (CN), aMCI, and AD. Methods: We acquired functional magnetic resonance spectroscopy (fMRS) data from 28 CN elderly, 16 aMCI and 12 AD subjects during a face-name association task. We measured fMRS metabolite ratios over 24 months in the 8-month apart, determined the temporal changes of the metabolites, and evaluated the differences among the three groups under the three different conditions (base, novel, repeat). Results: The results of comparisons for the three subject groups and the three-time points showed that tNAA/tCho and tCr/tCho were statistically significant among the three subject groups in any of the three conditions. The dynamic temporal change measurements for the metabolites for each condition showed that Glx/tCho and Glu/tCho levels at the third visit increased significantly compared with in the first visit in the novel condition in the AD group. Conclusion: We found declines in tNAA/tCho and tCr/tCho in the aMCI and AD subjects with increasing disease severity, being highest in CN and lowest in AD. The Glx/tCho level increased temporally in the AD subjects after they took an acetylcholine esterase inhibitor. Therefore, Glx may be suitable to demonstrate functional recovery after treatment.

scholarly journals P1240EVALUATION OF COGNITIVE FUNCTION IN HEMODIALYSIS PATIENTS USING MAGNETIC RESONANCE SPECTROSCOPY: FIVE YEARS FOLLOW UP RESULTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Shigeru Owada ◽  
Aki Hirayama ◽  
Teruhiko Maeba
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Future Research ◽  
Resonance Spectroscopy ◽  
Brain Metabolites ◽  
Dialysis Patients ◽  
Cont Group ◽  
The Brain

Abstract Background and Aims In Japan, the elderly population is increasing remarkably, and dialysis patients are aging as usual. According to statistics from the Japanese Society for Dialysis Therapy, at the end of 2017, the incidence of HD patients is estimated to be 3 per 1,000 population, and by the end of 2020, the average age will be over 70 years. Therefore, early diagnosis of cognitive impairment is an important issue. With the aging of dialysis patients, the number of cases showing cognitive dysfunction increase in addition to the decline of physical strength. The problem of the onset of dementia involves many difficulties in medical treatment and nursing. Magnetic resonance spectroscopy (MRS) has been progressing from 1970s to evaluate neurological functions by measuring metabolites in the brain non-invasively. There are few reports using MRS for dialysis patients. In this study, we investigated the brain metabolites of hemodialysis (HD) patients with or without cognitive impairments using MRS and evaluated its usefulness for the diagnosis of cognitive disorder. Method A Toshiba MR device of 1.5 T was used. PRESS sequence was used to acquire water-suppressed 1H-MRS. Timing was TR/TE 2000/25 ms. Three kinds of brain metabolites, namely N-acethylaspartate (NAA), creatine (Cr) and mioinositol (MI) in the posterior cingulate gyrus were measured for 25 healthy adults (Cont group, 44±16 y.o.) and 84 HD patients (HD group, 74±11 y.o.), and ratios of NAA/Cr, MI/Cr and MI/NAA were calculated. The concentration of each metabolite was analyzed using LC model. HD patients were classified into three groups, namely normal cognitive function group (HD-N, n=25, 72±16 y.o.), mild cognitive impairment (HD-M, n=29, 74±9 y.o.) and dementia (HD-D, n=30, 79±8 y.) using MMSE test. Also, sequential changes of the brain metabolites were evaluated for 13 patients with worse cognitive function prospectively. Results HD patients showed a significant decrease of NAA and increases of MI and MI/NAA ratios compared to those of Cont group, suggesting that some metabolic abnormalities were inducted in HD. With a detailed classification of cognitive function in HD patients, NAA/Cr ratios were 1.69±0.17, 1.57±0.15, 1.71±0.20 and 1.54±0.22 in Cont, HD-N, HD-M and HD-D groups, respectively, and was significantly lower even in HD-N group than that of Cont group. MI/Cr ratios were 0.78±0.21, 0.90±0.21, 0.95±0.28 and 1.02±0.27 in Cont, HD-N, HD-M and HD-D groups, respectively, and those of HD-N/-M/-D were significantly higher than that of Cont group. Also, the value of HD-D was significantly higher than those in the other groups. MI/NAA ratios were 0.46±0.13, 0.56±0.17, 0.54±0.16 and 0.66±0.15, in Cont, HD-N, HD-M and HD-D groups, respectively. Again, those of HD-N/-M/-D were significantly higher than that of Cont group. HD-D group was highest among the HD patients. In the prospective study, dementia progressed in 10 of 13 HD patients who were observed more than 5 years. The MI/NAA ratio increased in the patients with dementia progression (from 0.58±0.11 to 1.24±0.17) while that value of the patients without dementia progression showed no changes (from 0.51±0.14 to 0.55±0.18). Conclusion These result suggest that the measurement of metabolic fluctuation in the brain using MRS is useful for the diagnosis of cognitive function in HD patients. The MI/NAA value is a strong candidate for a predictive biomarker of dementia progression. In the future, research and development of measurements of various parts of the brain and their integration to show changes in the whole brain are desired.

scholarly journals Meta-Analysis of Neurochemical Changes Estimated via Magnetic Resonance Spectroscopy in Mild Cognitive Impairment and Alzheimer's Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Huanhuan Liu ◽  
Dandan Zhang ◽  
Huawei Lin ◽  
Qi Zhang ◽  
Ling Zheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Resonance Spectroscopy ◽  
Neurochemical Changes

The changes of neurochemicals in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients has been observed via magnetic resonance spectroscopy in several studies. However, whether it exists the consistent pattern of changes of neurochemicals in the encephalic region during the progression of MCI to AD were still not clear. The study performed meta-analysis to investigate the patterns of neurochemical changes in the encephalic region in the progress of AD. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases, and finally included 63 studies comprising 1,086 MCI patients, 1,256 AD patients, and 1,907 healthy controls. It showed that during the progression from MCI to AD, N-acetyl aspartate (NAA) decreased continuously in the posterior cingulate (PC) (SMD: −0.42 [95% CI: −0.62 to −0.21], z = −3.89, P < 0.05), NAA/Cr (creatine) was consistently reduced in PC (SMD: −0.58 [95% CI: −0.86 to −0.30], z = −4.06, P < 0.05) and hippocampus (SMD: −0.65 [95% CI: −1.11 to −0.12], z = −2.44, P < 0.05), while myo-inositol (mI) (SMD: 0.44 [95% CI: 0.26–0.61], z = 4.97, P < 0.05) and mI/Cr (SMD: 0.43 [95% CI: 0.17–0.68], z = 3.30, P < 0.05) were raised in PC. Furthermore, these results were further verified by a sustained decrease in the NAA/mI of PC (SMD: −0.94 [95% CI: −1.24 to −0.65], z = −6.26, P < 0.05). Therefore, the levels of NAA and mI were associated with the cognitive decline and might be used as potentially biomarkers to predict the possible progression from MCI to AD.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020200308.

Meta-analysis of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy

Neurology ◽  
2020 ◽  
Vol 94 (11) ◽  
pp. e1147-e1156 ◽  
Author(s):  
Georgia Zeng ◽  
Ross Penninkilampi ◽  
Joga Chaganti ◽  
Sara Montagnese ◽  
Bruce J. Brew ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Parietal Lobe ◽  
Meta Analysis ◽  
Brain Regions ◽  
Resonance Spectroscopy ◽  
Cochrane Central Register ◽  
Central Register ◽  
Mean Differences

ObjectiveVarious imaging modalities have been used to explore pathogenic mechanisms and stratify the severity of hepatic encephalopathy (HE). The hypothesis of this meta-analysis was that there is a progressive identifiable derangement of imaging measures using magnetic resonance spectroscopy (MRS) related to the severity of the HE.MethodsStudies with more than 10 cases and HE diagnosis were identified from the electronic databases PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Literatura Latino Americana em Ciências da Saúde (LILACS), and Cochrane Central Register of Controlled Trials (CENTRAL) through July 25, 2018. Participants were stratified into healthy controls and patients with non-HE (NHE) (cirrhosis without HE), minimal HE (MHE), and overt HE (OHE). Analyses were organized by metabolite studied and brain region examined. Statistical meta-analysis was performed using the metafor package in R (v3.4.1). Pooled standardized mean differences between patient groups were calculated using a random effects model.ResultsWe identified 31 studies (1,481 patients) that included data for cirrhosis-related HE. We found the parietal region to be the most reliable in differentiating between patients with and without MHE, with standard mean differences of +0.82 (95% confidence interval [CI] +0.49 to +1.15, p < 0.0001, I2 = 37.45%) for glutamine/glutamate, −0.36 (95% CI −0.61 to −0.10, p = 0.007, I2 = 20.00%) for choline, and−0.77 (95% CI −1.19 to −0.34, p = 0.0004, I2 = 67.48%) for myo-inositol. We also found that glutamine/glutamate was the metabolite that reliably correlated with HE grade in all brain regions.ConclusionsThe meta-analysis reveals that MRS changes in glutamine/glutamate, choline, and myo-inositol, particularly in the parietal lobe, correlate with the severity of HE. MRS may be of value in the assessment of HE.

scholarly journals Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration

2020 ◽  
Vol 20 (1) ◽  
pp. 2-11
Author(s):  
Amanda Eisele ◽  
MaryJane Hill-Strathy ◽  
Lars Michels ◽  
Katrin Rauen
Keyword(s):  
Systematic Review ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Frontal Lobe ◽  
Brain Metabolism ◽  
Meta Analysis ◽  
Resonance Spectroscopy

Introduction: Traumatic brain injury (TBI) is the most relevant external risk factor for dementia and a major global health burden. Mild TBI (mTBI) contributes to up to 90% of all TBIs, and the classification “mild” often misrepresents the patient’s burden who suffer from neuropsychiatric long-term sequelae. Magnetic resonance spectroscopy (MRS) allows in vivo detection of compromised brain metabolism although it is not routinely used after TBI. Objective: Thus, we performed a systematic review and meta-analysis to elucidate if MRS has the potential to identify changes in brain metabolism in adult patients after a single mTBI with a negative routine brain scan (CCT and/or MRI scan) compared to aged- and sex-matched healthy controls (HC) during the acute or subacute postinjury phase (≤90 days after mTBI). Methods: A comprehensive literature search was conducted from the first edition of electronic databases until January 31, 2020. Group analyses were performed per metabolite using a random-effects model. Results: Four and 2 out of 5,417 articles met the inclusion criteria for the meta-analysis and systematic review, respectively. For the meta-analysis, 50 mTBI patients and 51 HC with a mean age of 31 and 30 years, respectively, were scanned using N-acetyl-aspartate (NAA), a marker for neuronal integrity. Glutamate (Glu), a marker for disturbed brain metabolism, choline (Cho), a marker for increased cell membrane turnover, and creatine (Cr) were used in 2 out of the 4 included articles. Regions of interests were the frontal lobe, the white matter around 1 cm above the lateral ventricles, or the whole brain. NAA was decreased in patients compared to HC with an effect size (ES) of –0.49 (95% CI –1.08 to 0.09), primarily measured in the frontal lobe. Glu was increased in the white matter in 22 mTBI patients compared to 22 HC (ES 0.79; 95% CI 0.17–1.41). Cho was decreased in 31 mTBI patients compared to 31 HC (ES –0.31; 95% CI –0.81 to 0.19). Cr was contradictory and, therefore, potentially not suitable as a reference marker after mTBI. Conclusions: MRS pinpoints changes in posttraumatic brain metabolism that correlate with cognitive dysfunction and, thus, might possibly help to detect mTBI patients at risk for unfavorable outcome or posttraumatic neurodegeneration early.

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