Changes of brain metabolites in early Alzheimer’s disease: A high‐field magnetic resonance spectroscopy study on medication treatment effect

Abstract

AbstractBackgroundAD involves deficits in essential brain chemicals. A functional neurocompensatory response in brain regions critical for executive control has been reported for early AD. It is unclear whether such an effect can be detected in brain metabolites and affected by medication treatments. In this study, we used single‐voxel proton magnetic resonance spectroscopy (SV‐1H‐MRS, short as MRS here) to quantify neurochemical changes non‐invasively. Our objectives are to 1) examine differences in key neurometabolites between brain regions either compromised or preserved in early AD and 2) test the potential effect of medication treatment on metabolite levels in the brain regions.MethodSixteen participants with early AD (76.8±8.0 yrs, 56.2% female) and 20 normal controls (73.6 ± 6.3 yrs, 60% female) had two MRS sessions six months apart. AD patients took cholinesterase inhibitors as part of standard care following the baseline scan. MRS acquisition used 4T MRI with LASER sequence from two voxels (5.12cm3), respectively placed in the posterior cingulate gyri (PCG) and the left dorsolateral prefrontal cortex (DLPFC). Spectra data were fitted using fitMAN and analyzed using ANOVA for main effect and interactions (voxel placement, subject group, scan time).ResultThe level of many metabolites was greater in the DLPFC than in the PCG voxels (Fs>4.01, ps<0.050), regardless of the subject group. Participants with early AD had lower levels of NAA and Gln (absolute value and ratio to Cr) and higher Cr/NAA than controls across the brain regions (Fs>4.09, ps<0.047). Post‐treatment, a change in Ala/Cr, Gly/Cr, Gly/NAA, and Lac/NAA (Fs>4.04, ps<0.048). There was an increase in Syl only in the DLPFC voxel (Fs>6.71, ps<0.029), whereas there was a decrease in Gly/NAA in the PCG voxel (F = 11.47, p = 0.005). In contrast, in controls, NAAG in the PCG voxel decreased between baseline and follow‐up (Fs>5.08, ps<0.027).ConclusionThe data showed a lower level of several metabolites essential for maintaining neuronal function and connectivity in early AD than normal aging, especially in brain regions that are compromised early in the disease process. The study suggested a positive impact of clinical management of early AD on enabling neurocompensation for at least six months.