Examining Associations Between Smartphone Use and Clinical Severity in Frontotemporal Dementia: Proof-of-Concept Study
Authors: Paolillo Emily W , Casaletto Kaitlin B , Clark Annie L , Taylor Jack C , Heuer Hilary W , Wise Amy B , Dhanam Sreya , Sanderson-Cimino Mark , Saloner Rowan , Kramer Joel H , Kornak John , Kremers Walter , Forsberg Leah , Appleby Brian , Bayram Ece , Bozoki Andrea , Brushaber Danielle , Darby R Ryan , Day Gregory S , Dickerson Bradford C , Domoto-Reilly Kimiko , Elahi Fanny , Fields Julie A , Ghoshal Nupur , Graff-Radford Neill , G H Hall Matthew , Honig Lawrence S , Huey Edward D , Lapid Maria I , Litvan Irene , Mackenzie Ian R , Masdeu Joseph C , Mendez Mario F , Mester Carly , Miyagawa Toji , Naasan Georges , Pascual Belen , Pressman Peter , Ramos Eliana Marisa , Rankin Katherine P , Rexach Jessica , Rojas Julio C , VandeVrede Lawren , Wong Bonnie , Wszolek Zbigniew K , Boeve Bradley F , Rosen Howard J , Boxer Adam L , Staffaroni Adam M ,   ALLFTD Consortium
Published: June 2024

Background
Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown.

Objective
This study aims to characterize daily trajectories in smartphone battery use, a proxy for smartphone use, and examine relationships with clinical indicators of severity in FTLD.

Methods
Participants were 231 adults (mean age 52.5, SD 14.9 years; n=94, 40.7% men; n=223, 96.5% non-Hispanic White) enrolled in the Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL study) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS study) Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Mobile App study, including 49 (21.2%) with mild neurobehavioral changes and no functional impairment (ie, prodromal FTLD), 43 (18.6%) with neurobehavioral changes and functional impairment (ie, symptomatic FTLD), and 139 (60.2%) clinically normal adults, of whom 55 (39.6%) harbored heterozygous pathogenic or likely pathogenic variants in an autosomal dominant FTLD gene. Participants completed the Clinical Dementia Rating plus National Alzheimer’s Coordinating Center Frontotemporal Lobar Degeneration Behavior and Language Domains (CDR+NACC FTLD) scale, a neuropsychological battery; the Neuropsychiatric Inventory; and brain magnetic resonance imaging. The ALLFTD Mobile App was installed on participants’ smartphones for remote, passive, and continuous monitoring of smartphone use. Battery percentage was collected every 15 minutes over an average of 28 (SD 4.2; range 14-30) days. To determine whether temporal patterns of battery percentage varied as a function of disease severity, linear mixed effects models examined linear, quadratic, and cubic effects of the time of day and their interactions with each measure of disease severity on battery percentage. Models covaried for age, sex, smartphone type, and estimated smartphone age.

Results
The CDR+NACC FTLD global score interacted with time on battery percentage such that participants with prodromal or symptomatic FTLD demonstrated less change in battery percentage throughout the day (a proxy for less smartphone use) than clinically normal participants (P<.001 in both cases). Additional models showed that worse performance in all cognitive domains assessed (ie, executive functioning, memory, language, and visuospatial skills), more neuropsychiatric symptoms, and smaller brain volumes also associated with less battery use throughout the day (P<.001 in all cases).

Conclusions
These findings support a proof of concept that passively collected data about smartphone use behaviors associate with clinical impairment in FTLD. This work underscores the need for future studies to develop and validate passive digital markers sensitive to longitudinal clinical decline across neurodegenerative diseases, with potential to enhance real-world monitoring of neurobehavioral change.