Longitudinal brain atrophy rates in presymptomatic genetic frontotemporal dementia

Background In light of upcoming clinical trials for genetic frontotemporal dementia (FTD), it is important to identify at what age brain atrophy rates start accelerate and deviate from normal aging effects find the optimal starting point treatment. We aimed investigate longitudinal in presymptomatic stage FTD, using normative volumetry software. Method 34 GRN, eight MAPT, 14 C9orf72 mutation carriers underwent volumetric T1-weighted MRI with a one- two-year interval (mean number scans = 3.5, SD 1.6). Images were automatically analyzed Quantib® ND which consisted volume measurements (CSF grey + white matter) lobes (left, right, combined), cerebellum, hippocampus. All volumes compared reference centile curves based on large population-derived sample non-demented individuals (n 4951). Mixed-effects models fitted analyze different gene groups as function age, corrected sex, head coil, scanner software version. Result Atrophy total brain, frontal lobe, temporal lobe differed between (all p<0.002). GRN declined faster than all areas, though relative remained 5th 75th percentile ages 45 – 70. MAPT carriers, was already 45, showed further decline 50-60. Temporal started 50th but fastest over time other structures. Frontal, temporal, parietal cerebellar below there minimal until 60. Conclusion provide evidence FTD. The affected areas after diverge slopes groups. These results highlight value disease-tracking staging biomarkers