Abstract
BackgroundPET imaging of glucose metabolism has revealed presymptomatic abnormalities in genetic FTD but has not been explored in MAPT P301L mutation carriers. This study aimed to explore the patterns of presymptomatic hypometabolism and atrophy in MAPT P301L mutation carriers.MethodsEighteen asymptomatic members from five families with a P301L MAPT mutation were recruited to the study, six mutation carriers, and twelve mutation-negative controls. All participants underwent standard behavioural and cognitive assessment as well as [18F]FDG-PET and 3D T1-weighted MRI brain scans. Regional standardised uptake value ratios (SUVR) for the PET scan and volumes calculated from an automated segmentation for the MRI were obtained and compared between the mutation carrier and control groups.ResultsThe mean (standard deviation) estimated years from symptom onset was 12.5 (3.6) in the mutation carrier group with a range of 7 to 18 years. No differences in cognition were seen between the groups, and all mutation carriers had a global CDR plus NACC FTLD of 0. Significant reduction in [18F] FDG uptake in the anterior cingulate was seen in mutation carriers (mean 1.25 [standard deviation 0.07]) compared to controls (1.36 [0.09]). A similar significant reduction was also seen in grey matter volume in the anterior cingulate in mutation carriers (0.60% [0.06%]) compared to controls (0.68% [0.08%]). No other group differences were seen in other regions.ConclusionsAnterior cingulate hypometabolism and atrophy are both apparent presymptomatically in a cohort of P301L MAPT mutation carriers. Such a specific marker may prove to be helpful in stratification of presymptomatic mutation carriers in future trials.
Highlights
positron emission tomography (PET) imaging of glucose metabolism has revealed presymptomatic abnormalities in genetic Frontotemporal dementia (FTD) but has not been explored in microtubule-associated protein tau (MAPT) P301L mutation carriers
Several studies have identified presymptomatic changes in genetic FTD using a range of neuroimaging techniques, the majority of these have focused on structural, functional or perfusion magnetic resonance imaging (MRI) [6, 9,10,11, 21, 24]
We aimed to investigate whether presymptomatic neuronal dysfunction is present in P301L MAPT mutation carriers as measured by FDG-PET, and whether patterns of hypometabolism differed from patterns of atrophy
Summary
PET imaging of glucose metabolism has revealed presymptomatic abnormalities in genetic FTD but has not been explored in MAPT P301L mutation carriers. A third of all FTD is genetic, with the first described cause being mutations in the microtubule-associated protein tau (MAPT) gene in 1998 [13, 22, 27]. Studies of positron emission tomography (PET) imaging have been more limited, and mainly focused on [18F]-fluorodeoxyglucose (FDG-PET), a measure of glucose metabolism in vivo, where hypometabolism is thought to reflect neuronal dysfunction. In limited studies so far, FDGPET has revealed presymptomatic abnormalities in other genetic causes of FTD [2, 7, 8, 14], but not in P301L MAPT mutation carriers
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