Frontal lobe ¹H MR spectroscopy in asymptomatic and symptomatic <i>MAPT</i> mutation carriers.

Abstract

To determine the frontal lobe proton magnetic resonance spectroscopy (¹H MRS) abnormalities in asymptomatic and symptomatic carriers of microtubule-associated protein tau (<i>MAPT</i>) mutations. We recruited patients with <i>MAPT</i> mutations from 5 individual families, who underwent single voxel ¹H MRS from the medial frontal lobe at 3T (n = 19) from the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Study at the Mayo Clinic site. Asymptomatic <i>MAPT</i> mutation carriers (n = 9) had Frontotemporal Lobar Degeneration Clinical Dementia Rating Sum of Boxes (FTLD-CDR SOB) score of zero, and symptomatic <i>MAPT</i> mutation carriers (n = 10) had a median FTLD-CDR SOB score of 5. Noncarriers from healthy first-degree relatives of the patients were recruited as controls (n = 25). The demographic aspects and ¹H MRS metabolite ratios were compared by use of the Fisher exact test for sex and linear mixed models to account for within-family correlations. We used Tukey contrasts for pair-wise comparisons. Asymptomatic <i>MAPT</i> mutation carriers had lower neuronal marker N-acetylaspartate (NAA)/creatine (Cr) (<i>p</i> = 0.001) and lower NAA/myo-inositol (mI) (<i>p</i> = 0.026) than noncarriers after adjustment for age. Symptomatic <i>MAPT</i> mutation carriers had lower NAA/Cr (<i>p</i> = 0.01) and NAA/mI (<i>p</i> = 0.01) and higher mI/Cr (<i>p</i> = 0.02) compared to noncarriers after adjustment for age. Furthermore, NAA/Cr (<i>p</i> = 0.006) and NAA/mI (<i>p</i> < 0.001) ratios decreased, accompanied by an increase in mI/Cr ratio (<i>p</i> = 0.001), as the ages of carriers approached and passed the age at symptom onset. Frontal lobe neurochemical alterations measured with ¹H MRS precede the symptom onset in <i>MAPT</i> mutation carriers. Frontal lobe ¹H MRS is a potential biomarker for early neurodegenerative processes in <i>MAPT</i> mutation carriers.