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Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using 31P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment.

ABSTRACT: Background:The human brain has high energy requirements that continuously support healthy neuronal activity and cognition. A disruption in brain energy metabolism (BEM) may contribute to early neuropathological changes such as accumulation of ?-amyloid and tau in vulnerable populations. One such population is amnestic mild cognitive impairment (aMCI) where some individuals are at risk for developing dementia, i.e. Alzheimer's disease (AD). Recent advances in imaging technology are providing new avenues to measure BEM accurately using 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7-Tesla. This study investigates whether a methodology using partial volume-coil 31P MRS at 7T over parieto-occipital lobes can accurately quantify high-energy phosphate and membrane phospholipid metabolites in aMCI. A secondary objective was to explore BEM and membrane phospholipid indices' correspondence with cognitive performance in domains of executive function (EF), memory, attention, and visuospatial skills in aMCI, a heterogeneous population. Methods:19 aMCI participants enrolled in the study completed cognitive assessment and 31P MRS scan. BEM indices were measured using three energy indicators: energy reserve (PCr/t-ATP), energy consumption (intracellular_Pi/t-ATP), and metabolic state (PCr/intracellular_Pi) along with regulatory co-factors of BEM-intracellular Mg2 + and pH; whereas the ratio of phosphomonoesters (PMEs) to phosphodiesters (PDEs) - membrane phospholipid indicator. Results:31P MRS scan showed thirteen well-resolved peaks with precise quantification of the phosphorus metabolites at UHF. The higher BEM indices were associated with lower cognitive performance of memory [(energy reserve indicator: CVLT p = 0.004), (metabolic state indicator: CVLT p = 0.007)], executive function [(metabolic state indicator: TOSL (p = 0.044)], and attention [(pH: selective auditory task, p = 0.044)]. The finding of an inverse relationship observed in the parieto-occipital lobes suggests an association between neuronal energy markers with cognition in aMCI. Conclusion:The significant contribution of this preliminary research was to establish the feasibility of utilizing a methodology at UHF to accurately measure high-energy phosphate and membrane phospholipid metabolites in a population with heterogeneous outcomes. This work offers a novel approach for future work to further elucidate early dementia biomarkers or precursors to the downstream accumulation of amyloid and tau using the combination of MRS-PET imaging modalities in AD.

SUBMITTER: Das N

PROVIDER: S-EPMC7483543 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using <sup>31</sup>P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment.

Das Namrata N Ren Jimin J Spence Jeffrey S JS Rackley Audette A Chapman Sandra B SB

Frontiers in aging neuroscience 20200828

<h4>Background</h4>The human brain has high energy requirements that continuously support healthy neuronal activity and cognition. A disruption in brain energy metabolism (BEM) may contribute to early neuropathological changes such as accumulation of β-amyloid and tau in vulnerable populations. One such population is amnestic mild cognitive impairment (aMCI) where some individuals are at risk for developing dementia, i.e. Alzheimer's disease (AD). Recent advances in imaging technology are provid ...[more]

PMID: 33005142

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Project description:PurposePhosphorus (31 P) metabolites are emerging liver disease biomarkers. Of particular interest are phosphomonoester and phosphodiester (PDE) "peaks" that comprise multiple overlapping resonances in 31 P spectra. This study investigates the effect of improved spectral resolution at 7 Tesla (T) on quantifying hepatic metabolites in cirrhosis.MethodsFive volunteers were scanned to determine metabolite T1 s. Ten volunteers and 11 patients with liver cirrhosis were scanned at 7T. Liver spectra were acquired in 28?min using a 16-channel 31 P array and 3D chemical shift imaging. Concentrations were calculated using ?-adenosine-triphosphate (?-ATP)?=?2.65 mmol/L wet tissue.ResultsT1 means?±?standard deviations: phosphatidylcholine 1.05?±?0.28 s, nicotinamide-adenine-dinucleotide (NAD+ ) 2.0?±?1.0 s, uridine-diphosphoglucose (UDPG) 3.3?±?1.4 s. Concentrations in healthy volunteers: ?-ATP 2.74?±?0.11 mmol/L wet tissue, inorganic phosphate 2.23?±?0.20 mmol/L wet tissue, glycerophosphocholine 2.34?±?0.46 mmol/L wet tissue, glycerophosphoethanolamine 1.50?±?0.28?mmol/L wet tissue, phosphocholine 1.06?±?0.16 mmol/L wet tissue, phosphoethanolamine 0.77?± 0.14 mmol/L wet tissue, NAD+ 2.37?±?0.14 mmol/L wet tissue, UDPG 2.00?±?0.22 mmol/L wet tissue, phosphatidylcholine 1.38?±?0.31 mmol/L wet tissue. Inorganic phosphate and phosphatidylcholine concentrations were significantly lower in patients; glycerophosphoethanolamine concentrations were significantly higher (P?<?0.05).ConclusionWe report human in vivo hepatic T1 s for phosphatidylcholine, NAD+ , and UDPG for the first time at 7T. Our protocol allows high signal-to-noise, repeatable measurement of metabolite concentrations in human liver. The splitting of PDE into its constituent peaks at 7T may allow more insight into changes in metabolism. Magn Reson Med 78:2095-2105, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Project description:IntroductionMitochondrial dysfunction is a neurometabolic hallmark signaling abnormal brain energy metabolism (BEM) targeted as a potential early marker of Alzheimer's disease (AD). Advanced imaging technologies, such as 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7T, provide sensitive phosphate-BEM (p-BEM) data with precision. The study's first goal was to develop a methodology to measure phosphate energy and membrane metabolites simultaneously across the whole-brain using volume-coil 31P MRS at 7T in three groups-cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and AD. The second aim investigated whether p-BEM markers in the four brain regions-frontal, temporal, parietal, and occipital were significantly different across the three groups. The final goal examined correspondence between the p-BEM markers and cognition in the three groups.MethodsForty-one participants (CN = 15, aMCI = 15, AD = 11) were enrolled and completed cognitive assessment and scan. The cognitive domains included executive function (EF), memory, attention, visuospatial skills, and language. The p-BEM markers were measured using energy reserve index (PCr/t-ATP), energy consumption index (intracellular_Pi/t-ATP), metabolic state indicator (intracellular_Pi/PCr), and regulatory co-factors [magnesium (Mg2+) and intracellular pH].ResultsThirteen metabolites were measured simultaneously from the whole brain for all three group with high spectral resolution at UHF. In the aMCI group, a lower p-BEM was observed compared to CN group based on two markers, i.e., energy reserve (p = 0.009) and energy consumption (p = 0.05) indices; whereas in AD a significant increase was found in metabolic stress indicator (p = 0.007) and lower Mg2+ (p = 0.004) in the temporal lobes compared to aMCI using ANOVA between group analytical approach. Finally, using a linear mixed model, a significant positive correlation was found between Mg2+ and cognitive performance of memory (p = 0.013), EF (p = 0.023), and attention (p = 0.0003) in CN but not in aMCI or AD.ConclusionTo our knowledge, this is the first study to show that it is possible to measure p-BEM in vivo with precision at UHF across the three groups. Moreover, the findings suggest that p-BEM may be compromised in aMCI even before an AD diagnosis, which in future studies should explore to examine whether this energy crisis contributes to some of the earliest neuropathophysiologic changes in AD.

Dataset Information

Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using 31P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment.

Publications

Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using <sup>31</sup>P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment.

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