Frontal lobe 1H MR spectroscopy in asymptomatic and symptomatic MAPT mutation carriers
| Autor: | Qin Chen, Christina Dheel, Jonathan Graff-Radford, Howie Rosen, Neill R. Graff-Radford, Leah K. Forsberg, Adam L. Boxer, David S. Knopman, Dana Haley, Debra Gearhart, Jeffrey L. Gunter, Zbigniew K. Wszolek, Ruth Kraft, Maria I. Lapid, Jeremy Syrjanen, David R. Jones, Ralitza H. Gavrilova, Timothy G. Lesnick, Kejal Kantarci, Julie A. Fields, Nirubol Tosakulwong, Bradley F. Boeve, Rosa Rademakers, Danielle Brushaber |
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| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
biology Clinical Dementia Rating business.industry Tau protein Case-control study Frontotemporal lobar degeneration medicine.disease Gastroenterology Asymptomatic 03 medical and health sciences symbols.namesake 0302 clinical medicine Frontal lobe Internal medicine medicine symbols biology.protein 030212 general & internal medicine Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery Fisher's exact test Frontotemporal dementia |
| Zdroj: | Neurology. 93:e758-e765 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.0000000000007961 |
| Popis: | ObjectiveTo determine the frontal lobe proton magnetic resonance spectroscopy (1H MRS) abnormalities in asymptomatic and symptomatic carriers of microtubule-associated protein tau (MAPT) mutations.MethodsWe recruited patients with MAPT 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 MAPT mutation carriers (n = 9) had Frontotemporal Lobar Degeneration Clinical Dementia Rating Sum of Boxes (FTLD-CDR SOB) score of zero, and symptomatic MAPT 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.ResultsAsymptomatic MAPT mutation carriers had lower neuronal marker N-acetylaspartate (NAA)/creatine (Cr) (p = 0.001) and lower NAA/myo-inositol (mI) (p = 0.026) than noncarriers after adjustment for age. Symptomatic MAPT mutation carriers had lower NAA/Cr (p = 0.01) and NAA/mI (p = 0.01) and higher mI/Cr (p = 0.02) compared to noncarriers after adjustment for age. Furthermore, NAA/Cr (p = 0.006) and NAA/mI (p < 0.001) ratios decreased, accompanied by an increase in mI/Cr ratio (p = 0.001), as the ages of carriers approached and passed the age at symptom onset.ConclusionFrontal lobe neurochemical alterations measured with 1H MRS precede the symptom onset in MAPT mutation carriers. Frontal lobe 1H MRS is a potential biomarker for early neurodegenerative processes in MAPT mutation carriers. |
| Databáze: | OpenAIRE |
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