Gyrification abnormalities in young adult presymptomatic carriers of frontotemporal lobar degeneration mutations.

Background: Presymptomatic C9orf72 expansion carriers show regions of low local gyrification index (lGI) as early as their thirties (Caverzasi et al. JNNP 2019) and regions of gyrification decline have been reported (van Veenhuijzen et al. Ann Neurol 2022). These findings raise the question as to whether abnormal gyrification represents a neurodevelopmental difference or early neurodegeneration in frontotemporal lobar degeneration (FTLD) mutation carriers. Yet, previous studies focusing on young adults is lacking and no study has explored gyrification in the two other common FTLD mutations, GRN and MAPT. Here, we analyzed lGI in young adult presymptomatic FTLD mutation carriers. Method: LGI quantifies buried cortex within the sulcal folds compared to the visible cortex on the outer surface, with larger values indicating more folding (Schaer et al. IEEE trans med imaging 2008). Mean lGI values, as measured by a parcel‐wise analysis implemented in FreeSurfer v.6.0, were compared between 31 presymptomatic (preSx) carriers (12 C9orf72, 13 MAPT, 6 GRN, mean age: 25.2 ± 3.91 years) and 28 demographically‐matched healthy controls (HC: mean age: 25.6 ± 3.8 years). We used ANCOVA to compare all presymptomatic carriers combined (preSxAll) and HC to identify regions with significant lGI differences regressing age, sex, education, handedness, total intracranial volume and scanner type as nuisance covariates. Significant group differences were analyzed by Dunnett's post‐hoc tests between each mutation subgroup and HC (p<0.05). Result: Compared to HC, preSxAll had higher mean gyrification in the right caudal (F = 5.07, p = 0.03) and rostral anterior cingulate (F = 6.22, p = 0.17), and lower lGI in the left middle temporal gyrus (F = 4.22, p = 0.046). Within these regions, post‐hoc analyses showed that preSx GRN had greater gyrification in the right caudal anterior cingulate (t = 2.57, p = 0.039, 95% CI = [0.005, 0.248]) and preSx C9orf72 had lower lGI in the left middle temporal gyrus (t = ‐3.14, p = 0.009, 95% CI = [‐0.37, ‐0.04]) vs. HC. Conclusion: Young adult FTLD mutation carriers displayed higher gyrification in the right anterior cingulate and lower gyrification in the left middle temporal gyrus compared to HC. Future studies in children will confirm the extent to which these gyrification abnormalities represent neurodevelopmental differences. [ABSTRACT FROM AUTHOR]