TY - JOUR
T1 - Multisite ALLFTD study modeling progressive empathy loss from the earliest stages of behavioral variant frontotemporal dementia
AU - the ALLFTD consortium
AU - Toller, Gianina
AU - Cobigo, Yann
AU - Callahan, Patrick
AU - Appleby, Brian S.
AU - Brushaber, Danielle
AU - Domoto-Reilly, Kimiko
AU - Forsberg, Leah K.
AU - Ghoshal, Nupur
AU - Graff-Radford, Jonathan
AU - Graff-Radford, Neil R.
AU - Grossman, Murray
AU - Heuer, Hilary W.
AU - Kornak, John
AU - Kremers, Walter
AU - Lapid, Maria I.
AU - Leger, Gabriel
AU - Litvan, Irene
AU - Mackenzie, Ian R.
AU - Pascual, Maria B.
AU - Ramos, Eliana M.
AU - Rascovsky, Katya
AU - Rojas, Julio C.
AU - Staffaroni, Adam M.
AU - Tartaglia, Maria C.
AU - Toga, Arthur
AU - Weintraub, Sandra
AU - Wszolek, Zbigniew K.
AU - Boeve, Brad F.
AU - Boxer, Adam L.
AU - Rosen, Howard J.
AU - Rankin, Katherine P.
N1 - Funding Information:
HJR: has received research support from Biogen Pharmaceuticals, has consulting agreements with Wave Neuroscience and Ionis Pharmaceuticals, and receives research support from NIH.
Funding Information:
KDR: research support from NIH. She has served as an investigator for clinical
Funding Information:
ALB: research support from NIH, the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Association for Frontotemporal Degeneration and the Alzheimer's Association. He has served as a consultant for Abbvie, AGTC, Alector, Arkuda, Arvinas, Asceneuron, AZTherapeutics, Bioage, Ionis, Lundbeck, Passage BIO, Regeneron, Samumed, Transposon, and UCB, and received research support from Biogen, Eisai, Eli Lilly, Genentech, Novartis, Roche, and TauRx.
Funding Information:
NG: research support from NIH, the Association for Frontotemporal Degeneration, and Tau Consortium. She has participated in multicenter therapy studies by sponsored by Bristol Myers Squibb, Lilly, Janssen, Novartis, Pfizer, and Wyeth.
Funding Information:
ZKW: is partially supported by the Mayo Clinic Center for Regenerative Medicine; gifts from The Sol Goldman Charitable Trust, and the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson's Research Foundation. He served/s as PI or Co‐PI on Abbvie, Inc. (M15‐562 and M15‐563), Biogen, Inc. (228PD201) grant, and Biohaven Pharmaceuticals, Inc. (BHV4157‐206 and BHV3241‐301). He serves as PI of the Mayo Clinic American Parkinson Disease Association (APDA) Information and Referral Center, and as Co‐PI of the Mayo Clinic APDA Center for Advanced Research. He is a Co‐Editor‐in‐Chief of the (). He is a former Co‐Editor‐in‐Chief of , and former Associated Editor of the . Neurologia i Neurochirurgia Polska Polish Journal of Neurology and Neurosurgery Parkinsonism and Related Disorders European Journal of Neurology
Funding Information:
AMS: research support from NIA‐NIH and Larry L. Hillblom Foundation.
Funding Information:
KPR: receives research funding from NIH, Quest Diagnostics, Rainwater Charitable Foundation, and Marcus Family Foundation.
Funding Information:
BFB: research support from NIH, and research support for clinical trials sponsored by Biogen, Alector, and EIP Pharma. He serves on the Scientific Advisory Board of the Tau Consortium.
Funding Information:
MG: receives research support from NIH, Avid, and Piramal. He participates in clinical trials sponsored by Biogen, TauRx, and Alector; serves as a consultant to Bracco and UCB; and serves on the editorial board of . Neurology
Funding Information:
BSA: research support from the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and Ionis.
Funding Information:
Data collection and dissemination of the data presented in this manuscript were supported by the ARTFL‐LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Consortium (U19: AG063911, funded by the National Institute on Aging and the National Institute of Neurological Diseases and Stroke), the former ARTFL & LEFFTDS Consortia (ARTFL: U54 NS092089, funded by the National Institute of Neurological Diseases and Stroke and National Center for Advancing Translational Sciences; LEFFTDS: U01 AG045390, funded by the National Institute on Aging and the National Institute of Neurological Diseases and Stroke), grant R01AG029577 funded by the National Institute on Aging, as well as grant P300P1_177667 from the Swiss National Science Foundation. The manuscript has been reviewed by the ALLFTD Executive Committee for scientific content. The authors acknowledge the invaluable contributions of the study participants and families as well as the assistance of the support staff at each of the participating sites.
Publisher Copyright:
© 2022 the Alzheimer's Association.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
KW - Interpersonal Reactivity Index
KW - behavioral variant frontotemporal dementia
KW - clinical trials
KW - cognitive empathy
KW - emotional empathy
KW - volumetric MRI
UR - http://www.scopus.com/inward/record.url?scp=85145396751&partnerID=8YFLogxK
U2 - 10.1002/alz.12898
DO - 10.1002/alz.12898
M3 - Article
C2 - 36591730
AN - SCOPUS:85145396751
SN - 1552-5260
VL - 19
SP - 2842
EP - 2852
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 7
ER -