Longitudinal changes in network homogeneity in presymptomatic C9orf72 mutation carriers

The risk for carriers of repeat expansion mutations in C9orf72 to develop amyotrophic lateral sclerosis and frontotemporal dementia increases with age. Functional magnetic resonance imaging studies have shown reduced connectivity in symptomatic carriers, but it is not known whether connectivity declines throughout life as an acceleration of the normal aging pattern. In this study, we examined intra-network homogeneity (NeHo) in 5 functional networks in 15 presymptomatic C9+ carriers over an 18-month period and compared to repeated scans in 34 healthy controls and 27 symptomatic C9+ carriers. The longitudinal trajectory of NeHo in the somatomotor, dorsal attention, and default mode networks in presymptomatic carriers differed from aging controls and symptomatic carriers. In somatomotor networks, NeHo increased over time in regions adjacent to regions where symptomatic carriers had reduced NeHo. In the default network, the posterior cingulate exhibited age-dependent increases in NeHo. These findings are evidence against the proposal that the decline in functional connectivity seen in symptomatic carriers represents a lifelong acceleration of the healthy aging process.