Multisite ALLFTD study modeling progressive empathy loss from the earliest stages of behavioral variant frontotemporal dementia

• Published in: Alzheimer's & dementia Vol. 19; no. 7; pp. 2842 - 2852
• Main Authors: Toller, Gianina, Cobigo, Yann, Callahan, Patrick, Appleby, Brian S., Brushaber, Danielle, Domoto‐Reilly, Kimiko, Forsberg, Leah K., Ghoshal, Nupur, Graff‐Radford, Jonathan, Graff‐Radford, Neil R., Grossman, Murray, Heuer, Hilary W., Kornak, John, Kremers, Walter, Lapid, Maria I., Leger, Gabriel, Litvan, Irene, Mackenzie, Ian R., Pascual, Maria B., Ramos, Eliana M., Rascovsky, Katya, Rojas, Julio C., Staffaroni, Adam M., Tartaglia, Maria C., Toga, Arthur, Weintraub, Sandra, Wszolek, Zbigniew K., Boeve, Brad F., Boxer, Adam L., Rosen, Howard J., Rankin, Katherine P.
• Format: Journal Article
• Language: English
• Published: United States 01.07.2023
• Subjects: Atrophy; behavioral variant frontotemporal dementia; clinical trials; cognitive empathy; emotional empathy; Empathy; Frontotemporal Dementia - diagnosis; Humans; Interpersonal Reactivity Index; Magnetic Resonance Imaging; Neuropsychological Tests; volumetric MRI; behavioral variant frontotemporal dementia; Interpersonal Reactivity Index; clinical trials; emotional empathy; volumetric MRI; cognitive empathy
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1002/alz.12898

Introduction Empathy relies on fronto‐cingular and temporal networks that are selectively vulnerable in behavioral variant frontotemporal dementia (bvFTD). This study modeled when in the disease process empathy changes begin, and how they progress. Methods Four hundred thirty‐one individuals with asymptomatic genetic FTD (n = 114), genetic and sporadic bvFTD (n = 317), and 163 asymptomatic non‐carrier controls were enrolled. In sub‐samples, we investigated empathy measured by the informant‐based Interpersonal Reactivity Index (IRI) at each disease stage and over time (n = 91), and its correspondence to underlying atrophy (n = 51). Results Empathic concern (estimate = 4.38, 95% confidence interval [CI] = 2.79, 5.97; p < 0.001) and perspective taking (estimate = 5.64, 95% CI = 3.81, 7.48; p < 0.001) scores declined between the asymptomatic and very mild symptomatic stages regardless of pathogenic variant status. More rapid loss of empathy corresponded with subcortical atrophy. Discussion Loss of empathy is an early and progressive symptom of bvFTD that is measurable by IRI informant ratings and can be used to monitor behavior in neuropsychiatry practice and treatment trials.