Whole-Brain Metabolic Abnormalities Are Associated With Mobility in Older Adults With Multiple Sclerosis

Abstract

Background: Older adults with multiple sclerosis (MS) experience mobility impairments, but conventional brain imaging is a poor predictor of walking abilities in this population.

Objective: To test whether brain metabolites measured with Magnetic Resonance Spectroscopy (MRS) are associated with walking performance in older adults with MS.

Methods: Fifteen older adults with MS (mean age: 60.9, SD: 5.1) and 22 age-matched healthy controls (mean age: 64.2, SD: 5.7) underwent whole-brain MRS and mobility testing. Levels of N-acetylaspartate (NAA), myo-inositol (MI), choline (CHO), and temperature in 47 brain regions were compared between groups and correlated with walking speed (Timed 25 Foot Walk) and walking endurance (Six-Minute Walk).

Results: Older adults with MS had higher MI in 23 areas, including the bilateral frontal (right: t (21.449) = -2.605, P = .016; left: t (35) = -2.434, P = .020), temporal (right: t (35) = -3.063, P = .004; left: t (35) = -3.026, P = .005), and parietal lobes (right: t (21.100) = -2.886, P = .009; left: t (35) = -2.507, P = .017), and right thalamus (t (35) = -2.840, P = .007). MI in eleven regions correlated with walking speed, and MI in twelve regions correlated with walking endurance. NAA was lower in MS in the bilateral thalami (right: t (35) = 3.449, P < .001; left: t (35) = 2.061, P = .047), caudate nuclei (right: t (33) = 2.828, P = .008; left: t (32) = 2.132, P = .041), and posterior cingulum (right: t (35) = 3.077, P = .004; left: t (35) = 2.972, P = .005). NAA in four regions correlated with walking speed and endurance. Brain temperature was higher in MS patients in four regions, but did not correlate with mobility measures. There were no group differences in CHO.

Conclusion: MI and NAA may be useful imaging end-points for walking ability as a clinical outcome in older adults with MS.

Keywords: brain temperature; magnetic resonance spectroscopy; mobility; multiple sclerosis; older adults.

Figure 1.

Average MI/CR ratios in the groups of older healthy controls (left) and older adults with multiple sclerosis (right). Metabolite maps are overlaid on an MNI standard brain for reference. Representative integrated spectra in the right thalamus from one participant in each group are displayed, showing decreased NAA in the Multiple Sclerosis patient. CHO=choline, CR=creatine, MI=myo-inositol, NAA=N-Acetylaspartate, ppm=parts per million

Figure 2.

Relationships between MI/CR and walking speed on the Timed 25-foot Walk (T25FW) in four distinct brain regions.