Frontal adenosine triphosphate markers from 31P MRS are associated with cognitive performance in healthy older adults: preliminary findings

Abstract

Aging is associated with declines in mitochondrial efficiency and energy production which directly impacts the availability of adenosine triphosphate (ATP), which contains high energy phosphates critical for a variety of cellular functions. Previous phosphorous magnetic resonance spectroscopy (³¹P MRS) studies demonstrate cerebral ATP declines with age. The purpose of this study was to explore the functional relationships of frontal and posterior ATP levels with cognition in healthy aging. Here, we measured frontal and posterior ATP levels using ³¹P MRS at 3 Tesla (3 T) and assessed cognition using the Montreal Cognitive Assessment (MoCA) in 30 healthy older adults. We found that greater frontal, but not posterior, ATP levels were significantly associated with better MoCA performance. This relationship remained significant after controlling for age, sex, years of education, and brain atrophy. In conclusion, our findings indicate that cognition is related to ATP in the frontal cortex. These preliminary findings may have important implications in the search for non-invasive markers of in vivo mitochondrial function and the impact of ATP availability on cognition. Future studies are needed to confirm the functional significance of regional ATP and cognition across the lifespan.

Keywords: adenosine triphosphate; aging; brain energy metabolism; cognition; phosphorous magnetic resonance spectroscopy.

FIGURE 1

Example of voxel placements for panel (A) frontal and (B) posterior regions of the brain in left sagittal, coronal, and axial view. Yellow boxes represent the location of the voxel collected.

FIGURE 2

Representative ³¹P MRS spectra. From top to bottom: (residue) the difference between the estimated curve and the original curve; (individual components) representation of ³¹P metabolite peaks including 1 = PME, 2 = Pi, 3 = PDE, 4 = PCr, 5 = gamma ATP, 6 = alpha ATP, 7 = beta ATP; (estimate) spectrum generated after jMRUI/AMARES processing; (original) ³¹P spectrum obtained in the frequency domain in parts per million (ppm).

FIGURE 3

Scatterplots of the relationship between ATP TP ratios and MoCA total scores. (A) Frontal ATP TP ratios; (B) Posterior ATP TP ratios; R² reflects variance explained from the partial correlation between regional ATP TP ratios and MoCA total scores; X-axis = standardized residual of ATP TP ratios after controlling for age, sex, education, and CSF fraction; Y-axis = MoCA total scores.