Elsevier

Biological Psychiatry

Volume 75, Issue 9, 1 May 2014, Pages 686-692
Biological Psychiatry

Archival Report
APOE Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites in the Aging Brain

https://doi.org/10.1016/j.biopsych.2013.05.022Get rights and content

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 years old who were genotyped for APOE genetic polymorphism. Measurements of 1H-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures of general cognitive functioning, memory, executive function, semantic fluency, and speed of processing were also obtained.

Results

General linear model analysis demonstrated that older APOE E4 carriers had significantly higher choline/creatine and myo-inositol/creatine ratios than APOE E3 homozygotes. Structural equation modeling resulted in a model with an excellent goodness of fit and in which the APOE × age interaction and APOE status each had a significant effect on 1H-MRS metabolites (choline/creatine and myo-inositol/creatine). Furthermore, the APOE × age variable modulation of cognition was mediated by 1H-MRS metabolites.

Conclusions

In a healthy aging normal population, choline/creatine and myo-inositol/creatine ratios were significantly increased in APOE E4 carriers, suggesting the presence of neuroinflammatory processes and greater membrane turnover in older carriers. Structural equation modeling analysis confirmed these possible neurodegenerative markers and also indicated the mediator role of these metabolites on cognitive performance among older APOE E4 carriers.

Section snippets

Participants

Participants (n = 112) were cognitively healthy subjects recruited at the Litwin-Zucker Research Center for the Study of Alzheimer’s Disease and Memory Related Disorders. All potential participants underwent examination by a neurologist or a geriatric psychiatrist to determine study eligibility. All subjects were between the ages of 50 and 86 years, had Mini-Mental State Examination score ≥24, and did not meet Petersen’s criteria for MCI (see Supplement 1 for a detailed description of

Demographic and Cognitive Characteristics

Demographic characteristics and cognitive composite scores stratified by APOE status (carriers of the APOE E4 allele vs. E3 homozygotes) and age as based on a median split of the sample (<65 years vs. ≥65 years) are provided in Table 1 (age was split for presentation purposes in this table). Age range was 50 to 64 years (SD = 4.66) for the subjects younger than 65 years and 65 to 86 years (SD = 5.90) for the subjects older than 65 years. Gender distribution showed an imbalance in the APOE E4

Discussion

This is the first study to find significant APOE genotype effects on 1H-MRS metabolites in a healthy aging population. Specifically, GLM analyses indicated that Cho/Cr and mI/Cr ratios were influenced by an APOE × age interaction (such that older APOE E4 carriers had higher ratios than other subgroups). In addition, Cho/Cr ratio was independently modulated by a main effect of APOE (E4 carriers had higher ratios than E3/E3 homozygotes), and mI/Cr ratio was independently modulated by a main

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