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 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 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 Mg 2+ 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.

Phosphate Brain Energy Metabolism and Cognition in Alzheimer’s Disease: A Spectroscopy Study Using Whole-Brain Volume-Coil 31Phosphorus Magnetic Resonance Spectroscopy at 7Tesla

“…The present work adds to prior work of post-mortem findings of low Mg 2+ in the brain's vulnerable region using an in vivo technique. The use of UHF has enabled to have a high resolution of αand β-ATP signal, which appeared to be an easy-to-fit singlet they are more complicated as doublet and triplet, respectively, at the lower field at 1.5-T and 3T (Das et al, 2020). Therefore, measuring Mg 2+ levels precisely could add a new dimension to have a comprehensive approach to understand the role of regulatory co-factors on the p-BEM mechanism, a mitochondrial function.…”

“…In contrast, the cellular pH and Mg 2+ concentration were derived from the chemical shift measurements in region summed spectra for the four brain regions of interest-frontal, temporal, parietal, and occipital lobes. For each spectrum, the free intracellular magnesium (Mg 2+ ) concentration was calculated using the chemical shift difference between αand β-ATP (δ α−β in ppm), whereas pH was calculated from the chemical shift of the corresponding Pi (internal) peaks (δ Pi , in ppm) in reference to PCr (δ PCr = 0ppm) (Das et al, 2020). Total-ATP (t-ATP) signal was calculated by averaging the α-, β-, and γ-ATP resonances.…”

“…(PMEs/PDEs) (for definition of the terminology refer to our previous publication Das et al, 2020). The BEM markers, membrane phospholipid indices, and regulatory co-factors were transformed into a shifted log scale to symmetrize their respective distributions and reduce high-leverage contributions in individual values regressions.…”

“…At UHF magnetic strength 7T, the first aim of this research was to test the feasibility to acquire high quality whole-brain data for resolving phosphate brain energy and membrane metabolites from each voxel simultaneously across the three cohorts cognitively normal (CN) adults, aMCI, and mild AD using volume-coil 31 P MRS. Our second aim was to investigate if p-BEM and membrane phospholipid markers differ across those three groups in the four regions-frontal, temporal, parietal, and occipital bilaterally. The p-BEM markers were measured using the three indices-energy reserve index (PCr/t-ATP), energy consumption index (intracellular_Pi/t-ATP), and metabolic state indicator (intracellular_Pi/PCr), along with regulatory co-factors -magnesium (Mg 2+ ) and pH, separately (definitions of the three indices are cited in our previous publication; Das et al, 2020). Based on the prior study's findings using either 18 FDG-PET (Silverman et al, 2001;Mosconi et al, 2010;Mosconi, 2013;Ou et al, 2019) or 31 P MRS (Rijpma et al, 2018), which supported reduced respective BEM (glucose or phosphate) in the temporal lobes in MCI and AD, we hypothesized that p-BEM markers-energy reserve, energy consumption indices, and regulatory co-factors (Mg 2+ and pH), would be lower in the same vulnerable region of the brain and the same population, i.e., aMCI and AD when compared to CN group.…”

Snoring Remediation with Oral Appliance Therapy Potentially Reverses Cognitive Impairment: An Intervention Controlled Pilot Study

“…Informed consent was provided and signed by all eligible participants in approved guidelines with UTSW, UTD and TAMUCOD IRBs. A detailed description of the neurocognitive tests used was published [ 21 ].…”