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

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

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.

The Correlation Between Caffeine Intake and Brain Health in Cognitively Normal Healthy Older Adults

Objectives Caffeine is associated with brain health, and it is suggested to lower the risk of neurological diseases. This cross-sectional study aimed to investigate the association between caffeine intake and concentration of brain metabolites in healthy older adults. Methods Caffeine intake was determined in 60 cognitively normal, healthy older adults aged between 60–85 years (61.9% women) using a 7-day food record (7D) that was collected seven days prior to their Magnetic Resonance scan. The 7D was entered in the Nutrition Data System for Research (NDS-R version 2012) for nutrient analysis. Brain metabolites [N-acetylaspartate, creatine, total choline, glutamate + glutamine, and myo-inositol (mI)] were measured using a 1H magnetic resonance spectroscopic imaging method at 3T. All metabolites were quantified using LCModel analysis software and concentrations are shown as a ratio to creatine. Measurements were presented as mean ± standard deviation and n(%). We assessed the relationship between caffeine intake and brain metabolite concentrations by multiple linear regression, adjusting for age and sex. Statistical analyses were performed using SPSS (v25, IBM) with significance of P ≤ 0.05. Results Participants had a mean age of 69.3 ± 7.3 years. Mean caffeine intake among the participants was 152.17 ± 133.79mg/d (range: 0–635.98mg/d). There was a significant correlation between caffeine and mI (β = 0.443; P = 0.001). The remaining metabolites were not correlated with caffeine intake. Conclusions Higher caffeine intake in older adults was associated with higher brain mI concentrations. The metabolic link between brain mI concentrations and neurological diseases is still unclear, thus, future studies are necessary regarding the mechanism for the impact of caffeine on brain metabolism. Funding Sources This study is supported by funding from National Dairy Council (IYC). The Hoglund Brain Imaging Center is supported by grants from the NIH (C76 HF00201, P30 HD002528, S10 RR29577, UL1 TR000001, and P30AG035982) and the Hoglund Family Foundation.