Frontal lobe H MR spectroscopy in asymptomatic and symptomatic mutation carriers.

OBJECTIVE

To determine the frontal lobe proton magnetic resonance spectroscopy (H MRS) abnormalities in asymptomatic and symptomatic carriers of microtubule-associated protein tau () mutations.

METHODS

We recruited patients with mutations from 5 individual families, who underwent single voxel H 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 mutation carriers (n = 9) had Frontotemporal Lobar Degeneration Clinical Dementia Rating Sum of Boxes (FTLD-CDR SOB) score of zero, and symptomatic 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 H 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.

RESULTS

Asymptomatic mutation carriers had lower neuronal marker N-acetylaspartate (NAA)/creatine (Cr) ( = 0.001) and lower NAA/myo-inositol (mI) ( = 0.026) than noncarriers after adjustment for age. Symptomatic mutation carriers had lower NAA/Cr ( = 0.01) and NAA/mI ( = 0.01) and higher mI/Cr ( = 0.02) compared to noncarriers after adjustment for age. Furthermore, NAA/Cr ( = 0.006) and NAA/mI ( < 0.001) ratios decreased, accompanied by an increase in mI/Cr ratio ( = 0.001), as the ages of carriers approached and passed the age at symptom onset.

CONCLUSION

Frontal lobe neurochemical alterations measured with H MRS precede the symptom onset in mutation carriers. Frontal lobe H MRS is a potential biomarker for early neurodegenerative processes in mutation carriers.