Anterior cingulate metabolite levels, memory, and inhibitory control in abstinent men and women with Alcohol Use Disorder

Aims: Alcohol use disorder (AUD), has been shown to have harmful cognitive and physiological effects, including altered brain chemistry. Further, although men and women may differ in vulnerability to the neurobiological effects of AUD, results of existing studies have been conflicting. Brain metabolite levels and cognitive functions were examined in a cross section of men with AUD (AUDm) and women with AUD (AUDw) to determine degree of abnormalities after extended periods of abstinence (mean, six years), and to evaluate gender differences in cognitive and metabolite measures. Methods: Participants were 40 abstinent individuals with AUD (22 AUDw, 18 AUDm) and 50 age-equivalent non-AUD comparison participants (26 NCw, 24 NCm). Proton magnetic resonance spectroscopy (MRS) was employed at 3 Tesla to acquire metabolite spectra from the dorsal anterior cingulate cortex (dACC). Brain metabolites N-acetylaspartate (NAA), choline (Cho), myo-Inositol (mI), and glutamate & glutamine (Glx) were examined relative to measures of memory and inhibitory control. Results: Metabolite levels in the AUD group showed no significant differences from the NC group. Memory and inhibitory-control impairments were observed in the AUD group. There also were significant group-specific associations between metabolite ratios and measures of inhibitory control. There were no Group-by-Gender interactions for the four metabolite ratios. Conclusions: These findings demonstrate that brain metabolite levels in men and women with AUD, following long-term abstinence, do not differ from individuals without AUD. The data also provide evidence of associations between metabolite levels and measures of inhibitory control, a functional domain important for curtailing harmful drinking.

31P Transversal Relaxation Times and Metabolite Concentrations in the Human Brain at 9.4T

A method to estimate phosphorus (31P) transversal relaxation times (T2) of coupled spin systems is demonstrated. Additionally, intracellular and extracellular pH (pHext, pHint) and relaxation corrected metabolite concentrations are reported. Echo time (TE) series of 31P metabolite spectra were acquired using STEAM localization. Spectra were fitted using LCModel with accurately modeled Vespa basis sets accounting for J−evolution of the coupled spin systems. T2s were estimated by fitting a single exponential two−parameter model across the TE series. Fitted inorganic phosphate frequencies were used to calculate pH, and relaxation times were used to determine the brain metabolite concentrations. The method was demonstrated in the healthy human brain at a field strength of 9.4T. T2 relaxation times of ATP and NAD are the shortest between 8 ms and 20 ms, followed by T2s of inorganic phosphate between 25 ms and 50 ms, and PCr with a T2 of 100 ms. Phosphomonoesters and −diesters have the longest T2s of about 130 ms. Measured T2s are comparable to literature values and fit in a decreasing trend with increasing field strengths. Calculated pHs and metabolite concentrations are also comparable to literature values

A Pilot Study on the Cutoff Value of Related Brain Metabolite in Chinese Elderly Patients With Mild Cognitive Impairment Using MRS

Objective: This cross-sectional study aimed to distinguish patients with mild cognitive impairment (MCI) from patients with normal controls (NCs) by measuring the levels of N-acetyl aspartate (NAA), total creatinine (tCr), and choline (Cho) in their hippocampus (HIP) and their posterior cingulate gyrus (PCG) by using proton magnetic resonance spectroscopy (MRS) and to predict the cutoff value on the ratios of metabolites. We further aimed to provide a reference for the diagnosis of MCI in elderly patients in China.Methods: About 69 patients who underwent a clinical diagnosis of the MCI group and 67 patients with NCs, the Mini-Mental Status Examination (MMSE) score, the Montreal Cognitive Assessment (MoCA) score, and MRS of the bilateral HIP and bilateral PCG were considered. The ratio of NAA/tCr and Cho/tCr in the bilateral HIP and bilateral PCG was calculated. The relationship between the ratios of metabolites and the scores of MMSE and MoCA was analyzed, and the possible brain metabolite cutoff point for the diagnosis of MCI was evaluated.Results: Compared with the NC group, the scores of MMSE and MoCA in the MCI group decreased significantly (p < 0.05); the ratio of NAA/tCr in the bilateral HIP and bilateral PCG and the ratio of Cho/tCr at the right HIP in the MCI group decreased significantly (p < 0.05); however, there was no significant difference in the ratio of Cho/tCr in the left HIP and bilateral PCG between the two groups (p > 0.05). The correlation coefficient between MMSE/MoCA and the ratio of NAA/tCr was 0.49–0.56 in the bilateral HIP (p < 0.01). The best cutoff value of NAA/creatine (Cr) in the left HIP and the right HIP was 1.195 and 1.19. Sensitivity, specificity, and the Youden index (YDI) in the left HIP and the right HIP were (0.725, 0.803, 0.528) and (0.754, 0.803, 0.557), respectively.Conclusion: The level of metabolites in the HIP and the PCG of patients with MCI and of those with normal subjects has a certain correlation with the score of their MMSE and MoCA. When the value of NAA/tCr in the left HIP and right HIP is <1.19, it suggests that MCI may have occurred. According to this cutoff point, elderly patients with MCI in China could be screened.

Altered brain metabolite concentration and delayed neurodevelopment in preterm neonates

Background A very-low-birth-weight (VLBW) preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes. In this study, we investigated how neonatal brain metabolite concentrations changed with postmenstrual age and examined the relationship between changes in concentration (slopes) and neurodevelopmental level at 3–4 years. Methods We retrospectively examined 108 VLBW preterm infants who had brain single-voxel magnetic resonance spectroscopy at 34–42 weeks’ postmenstrual age. Neurodevelopment was assessed using a developmental test, and subjects were classified into four groups: developmental quotient <70, 70–84, 85–100, and >100. One-way analyses of covariance and multiple-comparison post hoc tests were used to compare slopes. Results We observed correlations between postmenstrual age and the concentrations of N-acetylaspartate and N-acetylaspartylglutamate (tNAA) (p < 0.001); creatine and phosphocreatine (p < 0.001); glutamate and glutamine (p < 0.001); and myo-inositol (p = 0.049) in the deep gray matter; and tNAA (p < 0.001) in the centrum semiovale. A significant interaction was noted among the tNAA slopes of the four groups in the deep gray matter (p = 0.022), and we found a significant difference between the <70 and 85–100 groups (post hoc, p = 0.024). Conclusions In VLBW preterm infants, the slopes of tNAA concentrations (adjusted for postmenstrual age) were associated with lower developmental quotients at 3–4 years. Impact In very-low-birth-weight preterm-born infants, a slower increase in tNAA brain concentration at term-equivalent age was associated with poorer developmental outcomes at 3–4 years. The increase in tNAA concentration in very-low-birth-weight infants was slower in poorer developmental outcomes, and changes in tNAA concentration appeared to be more critical than changes in tCho for predicting developmental delays. While tNAA/tCho ratios were previously used to examine the correlation with neurodevelopment at 1–2 years, we used brain metabolite concentrations.

Brain Metabolite, N-Acetylaspartate Is a Potent Protein Aggregation Inhibitor

Deposition of toxic protein inclusions is a common hallmark of many neurodegenerative disorders including Alzheimer's disease, Parkinson disease etc. N-acetylaspartate (NAA) is an important brain metabolite whose levels got altered under various neurodegenerative conditions. Indeed, NAA has been a widely accepted biological marker for various neurological disorders. We have also reported that NAA is a protein stabilizer. In the present communication, we investigated the role of NAA in modulating the aggregation propensity on two model proteins (carbonic anhydrase and catalase). We discovered that NAA suppresses protein aggregation and could solubilize preformed aggregates.