The Ignite app detects early cognitive impairment and tracks disease severity in genetic frontotemporal dementia

Background Ignite is an iPad-based cognitive assessment app designed to enhance the sensitivity of detecting early cognitive changes in presymptomatic frontotemporal dementia (FTD). It is intended for use as a remote outcome measure in future clinical trials. Before use in clinical trials, it is essential to establish the app’s sensitivity for detecting cognitive impairment and to evaluate its performance relative to established clinical measures. Methods A total of 569 participants from the Genetic FTD Initiative who completed Ignite during their annual research visit were included. Each participant also underwent a clinical assessment and a standard neuropsychological battery. Ignite scores were z-scored against a normative sample, and cognitive composite scores were calculated across distinct domains. Disease stage was defined using the CDR+NACC-FTLD global score including neuropsychiatric and motor components (CDR+NACC-FTLD-NM), where 0 = asymptomatic (N = 190), 0.5 = prodromal (N = 110), 1 = mildly symptomatic (N = 27) and ≥ 2 = moderately/severely symptomatic (N = 42). Linear regressions (adjusting for age, sex, and education) compared Ignite scores between healthy non-carriers (N = 200) and mutation carriers stratified by disease stage, with further analyses also conducted by genetic group ( C9orf72 , MAPT , and GRN ). Receiver operating characteristic (ROC) analyses were used to compare Ignite with standard neuropsychological composites. Results Ignite detected significant cognitive impairment in all symptomatic mutation carriers (CDR = 1 and CDR ≥ 2) across all six cognitive domains compared with non-carriers ( p  < 0.001). Prodromal mutation carriers (CDR = 0.5) showed impairments in all domains except social cognition, while asymptomatic carriers (CDR = 0) demonstrated reduced performance in executive function, social cognition, and calculation ( p  < 0.05). C9orf72 mutation carriers showed the earliest and broadest deficits across all cognitive domains, MAPT carriers exhibited pronounced impairments in semantic knowledge and social cognition, and GRN carriers demonstrated marked deficits in executive function and processing speed, particularly at symptomatic stages. ROC analyses demonstrated similarly good discrimination for Ignite and GENFI neuropsychology between symptomatic carriers and non-carriers across all cognitive domains (AUCs 0.91–0.92 for Ignite vs 0.89–0.93 for GENFI). Discrimination at the prodromal stage was lower for both measures, though Ignite showed higher AUCs across all domains (0.58–0.70 vs 0.55–0.64). Conclusions Ignite is a sensitive digital cognitive assessment capable of detecting early cognitive changes in genetic FTD and demonstrates improved discrimination compared with standard neuropsychological measures at milder disease severity. Its sensitivity to disease stage and gene-specific profiles, supports its potential utility as a scalable remote outcome measure for FTD clinical trials.