Hippocampal metabolites in asthma and their implications for cognitive function

Abstract

Emerging research indicates that individuals with asthma have an increased risk of cognitive impairment, yet the associations of asthma with neural correlates of memory remain relatively unknown. The hippocampus is the predominant neural structure involved in memory, and alterations in the hippocampal metabolic profile are observed in individuals with mild cognitive impairment. We therefore hypothesized that individuals with asthma may have altered hippocampal metabolites compared to healthy controls. Structural magnetic resonance imaging (sMRI) and proton magnetic resonance spectroscopy (¹H-MRS) were used to compare hippocampal volume and metabolites of otherwise healthy adults with and without asthma (N = 40), and to study the association of these measures with cognitive function and asthma-related variables. Participants underwent 3-Tesla sMRI and ¹H-MRS, with the volume of interest placed in the left hippocampus to measure levels of N-acetylaspartate (NAA), glutamate (Glu), creatine (Cr), and myo-inositol (MI), as indicators of neuronal viability, cellular activity, cellular energy reserve, as well as glial activation. Individuals with asthma had lower hippocampal NAA compared to healthy controls. For all participants, poorer cognitive function was associated with reduced NAA and Glu. For individuals with asthma, poorer cognitive function was associated with reduced disease control. Additionally, short-acting rescue bronchodilator use was associated with significantly lower NAA, and Glu, whereas inhaled corticosteroid use was related to significantly higher Cr and in tendency higher NAA and Glu. All findings controlled for left hippocampal volume, which was not different between groups. These findings highlight that asthma and/or its treatment may affect hippocampal chemistry. It is possible that the observed reductions in hippocampal metabolites in younger individuals with asthma may precede cognitive and hippocampal structural deficits observed in older individuals with asthma.

Keywords: 1H-MRS; Asthma; Cognition; Creatine; Glutamate; Hippocampus; N-acetylaspartate; Structural magnetic resonance imaging.

Fig. 1

MRI voxel placement and ¹H-MRS spectra from the hippocampus of a participant with asthma. Sagittal view demonstrates placement of the volume of interest in the left hippocampus. The area under the spectra represents the concentration of each metabolite in the identified tissue. Red line, baseline; blue line, in vivo data; green line, fit; light blue line, residual. Abbreviations: Cr, creatine; NAA, N-acetylaspartate; MI, myo-inositol; Glu, glutamate. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Group differences on total values of left hippocampal metabolites. Abbreviations: Cr, creatine; NAA, N-acetylaspartate; MI, myo-inositol; Glu, glutamate.

Fig. 3

Residual plots of left hippocampal metabolites and global cognitive function scores captured by the Montreal Cognitive Assessment, controlling for hippocampal volume in the entire sample. Statistics for Pearson partial correlations (two-tailed) displayed, controlling for left hippocampal volume. Abbreviations: Cr, creatine; NAA, N-acetylaspartate; MI, myo-inositol; Glu, glutamate.

Fig. 4

Residual plots of left hippocampal metabolites and frequency of short-acting bronchodilator use in the past week for the asthma group only, controlling for left hippocampal volume. Statistics for Pearson partial correlations (two-tailed) displayed, controlling for left hippocampal volume. Abbreviations: Cr, creatine; NAA, N-acetylaspartate; MI, myo-inositol; Glu, glutamate.

Fig. 5

Relations of Asthma Control Questionnaire (ACQ) and MoCA (Montreal Cognitive Assessment) scores. Pearson correlation (two-tailed) displayed.