Cerebral Metabolite Concentrations Are Associated With Cortical and Subcortical Volumes and Cognition in Older Adults

Lamb, Damon G.; Porges, Eric C.; Bottari, Sarah A; Woods, Adam J.; Datta, Somnath; Langer, Kailey; Cohen, Ronald A.

doi:10.3389/fnagi.2020.587104

Cited by 12 publications

(11 citation statements)

References 50 publications

(54 reference statements)

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“…Changes in the cerebral levels of those metabolites, following a fatty diet, have been reported in preclinical studies 21 and evidence exists that the consumption of a high caloric diet also leads to high concentrations of inflammatory cytokines in the brain, resulting in microgliosis, astrocytosis and neuronal damage 8 , 22 . Moreover, patients suffering from steatohepatitis have a reduced brain volume 23 and are at higher risk to suffer from neurological diseases, which are, most probably, related to the volume reductions as well 24 .…”

Section: Introductionmentioning

confidence: 99%

MAFLD progression contributes to altered thalamus metabolism and brain structure

Nucera

Ruga

Cardamone

et al. 2022

Sci Rep

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Metabolic associated fatty liver disease (MAFLD), commonly known as non-alcoholic fatty liver disease, represents a continuum of events characterized by excessive hepatic fat accumulation which can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and in some severe cases hepatocellular carcinoma. MAFLD might be considered as a multisystem disease that affects not only the liver but involves wider implications, relating to several organs and systems, the brain included. The present study aims to investigate changes associated with MAFLD-induced alteration of thalamic metabolism in vivo. DIAMOND (Diet-induced animal model of non-alcoholic fatty liver disease) mice were fed a chow diet and tap water (NC NW) or fat Western Diet (WD SW) for up to 28 weeks. At the baseline and weeks 4, 8, 20, 28 the thalamic neurochemical profile and total cerebral brain volume were evaluated longitudinally in both diet groups using 1H-MRS. To confirm the disease progression, at each time point, a subgroup of animals was sacrificed, the livers excised and placed in formalin. Liver histology was assessed and reviewed by an expert liver pathologist. MAFLD development significantly increases the thalamic levels of total N-acetylaspartate, total creatine, total choline, and taurine. Furthermore, in the WD SW group a reduction in total cerebral brain volume has been observed (p < 0.05 vs NC NW). Our results suggest that thalamic energy metabolism is affected by MAFLD progression. This metabolic imbalance, that is quantifiable by 1H-MRS in vivo, might cause structural damage to brain cells and dysfunctions of neurotransmitter release.

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Section: Introductionmentioning

confidence: 99%

MAFLD progression contributes to altered thalamus metabolism and brain structure

Nucera

Ruga

Cardamone

et al. 2022

Sci Rep

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“…As neurochemical changes may serve as a precursor to atrophy, it would follow that certain areas are more vulnerable to age-related metabolic changes than others. An investigation of the relationships between cerebral metabolites and both cortical and subcortical brain volumes in the same sample has recently been published and found divergent relationships between frontal and parietal metabolite concentrations and cortical and subcortical brain volumes (Williamson et al, 2021 ). Additionally, in many cases, cytokines are pleiotropic or act on each other which further complicates the interpretation of seemingly counterintuitive effects.…”

Section: Discussionmentioning

confidence: 99%

Circulating Cytokines Predict 1H-Proton MRS Cerebral Metabolites in Healthy Older Adults

Langer

Cohen

Porges

et al. 2021

Front. Aging Neurosci.

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Background: Changes in both circulating cytokines and neurochemical concentrations have been observed in aging. Patterns of change across these factors are associated with age-related pathologies, including neurodegenerative disease. More evidence to define patterns of change that are characteristic of healthy aging is needed, as is an investigation into how age-related changes in blood cytokines and brain neurochemicals may relate to one another in a healthy older adult population.Methods: Single voxel 1H-proton magnetic resonance spectroscopy was collected in medial frontal and medial parietal regions. Phosphocholine and glycerophosphocholine (Cho), myo-inositol (MI), N-acetylaspertate and N-acetylasperglutamate (NAA), creatine and phosphocreatine (Cr), and glutamate and glutamine (Glx) were measured in a sample of 83 healthy, cognitively normal adults aged 52–89. Blood data were collected to quantify 12 cytokines: interleukins (IL-) 2, 5, 6, 7, 8, 10, 12, 13, IL-1 β, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and IL-17 α. Correlation analyses were performed to assess age relationships between each of these factors. Backward linear regressions were performed. Cytokine data and age were used as predictors of each cerebrospinal fluid (CSF)-corrected metabolite concentration in both voxels.Results: Associations were identified between a variety of cytokines and concentrations of frontal NAA, Cr, and Glx, and of parietal MI, Cho, NAA, and Cr. In the frontal voxel, NAA was predicted by more IL-1B and less TNF-α, Cr by less TNF-α and more IL-5, and Glx by less TNF-α. In the parietal voxel, MI was predicted by more IL-10 and IL-8 and less IL-2, Cho by more TNF-α and less IL-2, NAA by more IL-1B and TNF-α and less IL-13, IL-2, and IL-7, and Cr by more IL-10 and less IL-2.Conclusions: Associations were identified between circulating cytokines and neurometabolite concentrations in this sample of older adults. The present results serve as the initial evidence of relationships between circulating cytokines and neurophysiology. Findings invite further investigation to understand the physiological consequences of aging, and how peripheral inflammatory markers may relate to neurochemical concentrations in healthy aging.

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“…Cortical thickness in the parietal region in CW appears to be larger than in CM [17]. As TM and CW show a similar developmental pattern in the parietal cortex [13,17], and because we expect volumetric changes to be reflected in altered metabolite concentration [58], we hypothesized that no differences exist between CW and TMGD regarding absolute metabolite levels and relative metabolite ratios in the parietal cortex. In the amygdala however, no volumetric differences have been reported in TM with respect to cisgender people.…”

Section: Introductionmentioning

confidence: 99%

“…A recent study by Williamson et al (2021) examined the relationship between cerebral metabolites, brain volume, and cognitive performance [58]. They found that cerebral metabolite concentrations are associated with cortical and subcortical volumes.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the 1H-MRS Metabolite Spectra in Transgender Men with Gender Dysphoria and Cisgender People

Collet

Bhaduri

Kiyar

et al. 2021

JCM

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Much research has been conducted on sexual differences of the human brain to determine whether and to what extent a brain gender exists. Consequently, a variety of studies using different neuroimaging techniques attempted to identify the existence of a brain phenotype in people with gender dysphoria (GD). However, to date, brain sexual differences at the metabolite level using magnetic resonance spectroscopy (1H-MRS) have not been explored in transgender people. In this study, 28 cisgender men (CM) and 34 cisgender women (CW) and 29 transgender men with GD (TMGD) underwent 1H-MRS at 3 Tesla MRI to characterize common brain metabolites. Specifically, levels of N–acetyl aspartate (NAA), choline (Cho), creatine (Cr), glutamate and glutamine (Glx), and myo-inositol + glycine (mI + Gly) were assessed in two brain regions, the amygdala-anterior hippocampus and the lateral parietal cortex. The results indicated a sex-assigned at birth pattern for Cho/Cr in the amygdala of TMGD. In the parietal cortex, a sex-assigned at birth and an intermediate pattern were found. Though assessed post-hoc, exploration of the age of onset of GD in TMGD demonstrated within-group differences in absolute NAA and relative Cho/Cr levels, suggestive for a possible developmental trend. While brain metabolite levels in TMGD resembled those of CW, some interesting findings, such as modulation of metabolite concentrations by age of onset of GD, warrant future inquiry.

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Cerebral Metabolite Concentrations Are Associated With Cortical and Subcortical Volumes and Cognition in Older Adults

Cited by 12 publications

References 50 publications

MAFLD progression contributes to altered thalamus metabolism and brain structure

MAFLD progression contributes to altered thalamus metabolism and brain structure

Circulating Cytokines Predict 1H-Proton MRS Cerebral Metabolites in Healthy Older Adults

Characterization of the 1H-MRS Metabolite Spectra in Transgender Men with Gender Dysphoria and Cisgender People

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