E. W. Paolillo, S. Dhanam, J. C. Taylor, M. Sanderson-Cimino, R. Fregly, R. Saloner, K. B. Casaletto, J. H. Kramer, B. L. Miller, W. W. Seeley, M. L. Gorno-Tempini, P. A. Ljubenkov, J. C. Rojas, S. Lee, V. Sturm, B. Appleby, E. Bayram, D. Clark, C. M. Considine, R. R. Darby, G. S. Day, A. De Vito, M. Eldaief, J. A. Fields, N. Ghoshal, E. D. Huey, D. J. Irwin, K. Kantarci, J. Y. Kwan, I. R. Mackenzie, J. C. Masdeu, C. U. Onyike, A. Pantelyat, B. Pascual, T. Popli, K. Rascovsky, N. Rezaii, S. W. Scholz, A. Snyder, M. C. Tartaglia, B. J. Traynor, B. Wong
Introduction: Frontotemporal lobar degeneration (FTLD) is a devastating disease that commonly results in early onset dementia, yet its rarity and heterogeneity limit large-scale research and clinical trials. Remote monitoring via low-burden digital health tools may overcome these barriers. We evaluated clinical utility of passive smartphone monitoring in FTLD using a multi-domain mobile assessment platform. Methods: Participants were 567 adults (53% clinically normal, 21% prodromal FTLD, 26% symptomatic FTLD) who completed an in-person study visit and downloaded the ALLFTD Mobile App on their personal smartphones. The app delivered unsupervised cognitive tests and passively collected continuous data on battery percentage (proxy for smartphone use) and step count. Longitudinal follow-up included smartphone monitoring and annual in-person study visits. Primary analyses examined associations between passive smartphone features and markers of disease severity at baseline and longitudinally, and tested whether passive features added incremental value beyond app-based cognitive testing. Results: Passive smartphone features were feasible to collect and showed excellent reliability with <2 weeks of monitoring (ICCs>0.9). Features capturing smartphone use and movement demonstrated sensitivity to gold-standard clinical measures of disease severity both at baseline and longitudinally. A classification model combining passive features, the app-based cognitive composite score, and demographics detected longitudinal functional decline (AUC=0.89); passive features alone (AUC=0.84) performed comparably to a cognitive screener (AUC=0.85). Discussion: Passive smartphone monitoring is a valid, zero-burden measure of disease severity and progression in FTLD that adds modest incremental value beyond app-based cognitive testing. Findings support its use as a scalable digital endpoint in longitudinal FTLD research.