2014
DOI: 10.1016/j.biopsych.2013.05.022
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APOE Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites in the Aging Brain

Abstract: Background Proton magnetic resonance spectroscopy (1H-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. Methods We studied a cohort of 112 normal adults between 50 and 86 y… Show more

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Cited by 31 publications
(36 citation statements)
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References 40 publications
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“…The associations of high Glx, mI, and GABA with low episodic memory performance did not remain significant after correction for multiple testing and, thus, need to be interpreted with caution. However, as mI is considered to be a glial marker of inflammation that has been reported to be increased in AD (Bitsch, et al, 1999,Miller, et al, 1993, and Glx, and GABA reflect activity of major cerebral neurotransmitter systems that also are affected by AD pathology (Gomar, et al, 2014,Kapogiannis and Mattson, 2011,Miller, et al, 1993,Olson, et al, 2008,Riese, et al, 2015, our findings might indicate a general increase of neuronal metabolic activity in a context of low episodic memory and thus be consistent with the effects observed for NAA. The fact that metabolic change was not associated with hippocampal or general brain atrophy may indicate potential reversibility due to absence of major neurodegenerative damage.…”
Section: Discussionsupporting
confidence: 85%
“…The associations of high Glx, mI, and GABA with low episodic memory performance did not remain significant after correction for multiple testing and, thus, need to be interpreted with caution. However, as mI is considered to be a glial marker of inflammation that has been reported to be increased in AD (Bitsch, et al, 1999,Miller, et al, 1993, and Glx, and GABA reflect activity of major cerebral neurotransmitter systems that also are affected by AD pathology (Gomar, et al, 2014,Kapogiannis and Mattson, 2011,Miller, et al, 1993,Olson, et al, 2008,Riese, et al, 2015, our findings might indicate a general increase of neuronal metabolic activity in a context of low episodic memory and thus be consistent with the effects observed for NAA. The fact that metabolic change was not associated with hippocampal or general brain atrophy may indicate potential reversibility due to absence of major neurodegenerative damage.…”
Section: Discussionsupporting
confidence: 85%
“…Another study by the same group looked at the contribution of the metabolites choline, myoinositol, and creatine in normal adults stratified according to age and APOEε4 genotype. They found that choline/creatine and myoinositol/creatine ratios were increased in older APOEε4 carriers and that the presence of these neurodegeneration markers was also linked to declining cognitive scores [34], an interesting finding that deserves replication.…”
Section: Novel Approaches and Clinical Meaningfulnessmentioning
confidence: 94%
“…Few other investigations have explored mediation effects of metabolites measured with MRS on cognitive function. Gomar et al [44] examined the precuneus in a sample older than 50 years of age and found that associations of Cho/Cre with a composite measure of broad cognitive ability varied as a function of APOE genotype (including APOE-4), but these investigators did not examine GABA. CSF and measures of Alzheimer pathology (e.g., estimates of amyloid concentration) were not included in this analysis.…”
Section: Association Of Cognitive Variables With Agementioning
confidence: 99%