Cross-country variance in facial emotion recognition in presymptomatic and symptomatic behavioral variant frontotemporal dementia: Insights from the GENFI and ReDLat consortia

Liset de Boer¹, Lize C Jiskoot¹, Harro Seelaar¹, John C van Swieten¹, Agustin Ibanez^{2

3}, Marcelo Maito², Sol Fittipaldi², Julie F H De Houwer¹, Tine Swartenbroekx¹, Pam A Boesjes¹, Rhian S Convery⁴, Eve Ferry-Bolder⁴, Phoebe Foster⁴, Arabella Bouzigues⁴, Lucy Chisman-Russell⁴, Esther van den Berg¹, Janne Papma^{1

5}, Sanne Franzen¹, Renelle Bourdage^{1

6}, James B Rowe⁷, Barbara Borroni^{8

9}, Daniela Galimberti^{10

11}, Pietro Tiraboschi¹², Mario Masellis¹³, Elizabeth Finger¹⁴, Robert Laforce¹⁵, Caroline Graff¹⁶, Alexander Gerhard¹⁷, Raquel Sanchez-Valle¹⁸, Alexandre Mendonça¹⁹, Fermin Moreno²⁰, Matthis Synofzik²¹, Rik Vandenberghe²², Simon Ducharme²³, Isabelle Le Ber²⁴, Johannes Levin^{25

26

27}, Thibaud Lebouvier²⁸, Benedetta Nacmias²⁹, Markus Otto³⁰, Christopher R Butler^{31

32}, Isabel Santana³³, Maxime Bertoux²⁸, M Carmela Tartaglia³⁴, Jonathan D Rohrer⁴, Jackie M Poos¹; GENFI Consortium

Affiliations

¹ Alzheimer Center, Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
² Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Peñalolén, Santiago de Chile, Chile.
³ Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland.
⁴ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
⁵ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁶ Université Paris Cité, Laboratoire Mémoire Cerveauet Cognition (UR7536), Institut de Psychologie, Boulogne-Billancourt, France.
⁷ Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.
⁸ Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa, Brescia, Italy.
⁹ Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
¹⁰ Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
¹¹ Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
¹² Fondazione IRCCS Institute Neurologico Carlo Besta, Milan, Italy.
¹³ Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada.
¹⁴ Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada.
¹⁵ Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, and Faculté de Médecine, Université Laval, Rue Québec (Qc), QC, Canada.
¹⁶ Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Bioclinicum, Karolinska Institutet, Solna, Sweden.
¹⁷ Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Withington, Manchester, UK.
¹⁸ Alzheimer's disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacións Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.
¹⁹ Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
²⁰ Cognitive Disorders Unit, Department of Neurology, Donostia Universitary Hospital, Donostia, San Sebastian, Spain.
²¹ Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.
²² Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
²³ Department of Psychiatry, Douglas Mental Health University Institute and Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
²⁴ Sorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié, Paris, France.
²⁵ Department of Neurology, LMU University Hospital, LMU, Munich, Germany.
²⁶ German Center for Neurodegenerative Diseases, site Munich, Munich, Germany.
²⁷ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
²⁸ Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, Inserm, Rue Michel Polonowski, Lille, France.
²⁹ Department of Neurofarba, University of Florence, Firenze, Italy.
³⁰ Department of Neurology, University of Ulm, Ulm, Germany.
³¹ Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK.
³² The George Institute for Global Health, School of Public Health, Imperial College London, London, UK.
³³ University Hospital of Coimbra (HUC), Neurology Service, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
³⁴ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.

PMID: 41085124
PMCID: PMC12519523
DOI: 10.1002/alz.70741

Cross-country variance in facial emotion recognition in presymptomatic and symptomatic behavioral variant frontotemporal dementia: Insights from the GENFI and ReDLat consortia

Liset de Boer et al. Alzheimers Dement. 2025 Oct.

. 2025 Oct;21(10):e70741.

doi: 10.1002/alz.70741.

Authors

Affiliations

¹ Alzheimer Center, Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
² Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Peñalolén, Santiago de Chile, Chile.
³ Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland.
⁴ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
⁵ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁶ Université Paris Cité, Laboratoire Mémoire Cerveauet Cognition (UR7536), Institut de Psychologie, Boulogne-Billancourt, France.
⁷ Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.
⁸ Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa, Brescia, Italy.
⁹ Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
¹⁰ Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
¹¹ Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
¹² Fondazione IRCCS Institute Neurologico Carlo Besta, Milan, Italy.
¹³ Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada.
¹⁴ Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada.
¹⁵ Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, and Faculté de Médecine, Université Laval, Rue Québec (Qc), QC, Canada.
¹⁶ Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Bioclinicum, Karolinska Institutet, Solna, Sweden.
¹⁷ Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Withington, Manchester, UK.
¹⁸ Alzheimer's disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacións Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.
¹⁹ Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
²⁰ Cognitive Disorders Unit, Department of Neurology, Donostia Universitary Hospital, Donostia, San Sebastian, Spain.
²¹ Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.
²² Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
²³ Department of Psychiatry, Douglas Mental Health University Institute and Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
²⁴ Sorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié, Paris, France.
²⁵ Department of Neurology, LMU University Hospital, LMU, Munich, Germany.
²⁶ German Center for Neurodegenerative Diseases, site Munich, Munich, Germany.
²⁷ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
²⁸ Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, Inserm, Rue Michel Polonowski, Lille, France.
²⁹ Department of Neurofarba, University of Florence, Firenze, Italy.
³⁰ Department of Neurology, University of Ulm, Ulm, Germany.
³¹ Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK.
³² The George Institute for Global Health, School of Public Health, Imperial College London, London, UK.
³³ University Hospital of Coimbra (HUC), Neurology Service, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
³⁴ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.

PMID: 41085124
PMCID: PMC12519523
DOI: 10.1002/alz.70741

Abstract

Introduction: We investigated international differences in facial emotion recognition (FER) across stages of frontotemporal dementia (FTD). Previous studies may have missed early decline by combining data and masking variations in FER across countries.

Methods: An FER test was administered to 159 individuals with behavioral variant FTD, 521 presymptomatic pathogenic variant carriers, and 583 controls from 16 countries of residence. Linear mixed models assessed age, sex, education, and country effects on FER. Voxel-based morphometry examined neural correlates across countries.

Reults: Country accounted for 18%-18.3% of FER variance in presymptomatic carriers and controls and 9.9% in individuals with behavioral variant of FTD (bvFTD). Cross-country differences interacted with the effects of sex, age, and education. Neural correlates involving the frontal lobe and basal ganglia were identified in individuals with bvFTD, but no cross-country differences were found.

Discussion: These results underscore the need for culturally sensitive FER tools in research and clinical practice, especially as global multinational clinical trials emerge.

Highlights: Performance on a test for facial emotion recognition (FER) varies between countries. The percentage of variance is lower in the behavioral variant of frontotemporal dementia (bvFTD) compared to presymptomatic pathogenic variant carriers and healthy controls. Cross-country differences interacted with the effects of sex, age, and education. There were no differences in brain correlates of FER across countries.

Keywords: cultural diversity; facial emotion recognition; frontotemporal dementia; presymptomatic; social cognition.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. Author disclosures are available in the Supporting Information.

Figures

**FIGURE 1**
Heatmap of the difference between every pair of countries measured with Hedge's g. Positive values correspond to a better performance of column countries compared to row countries.

**FIGURE 2**
Effects of sex, age, and education per country in healthy controls. Note: Dotted lines indicate a higher predicted FER total score in males compared to females. The effects of age and education on the predicted FER total score are visualized with 95% confidence intervals. FER, facial emotion recognition.

**FIGURE 3**
Effects of sex, age, and education per country in presymptomatic pathogenic variant carriers. Note: Dotted lines indicate a higher predicted FER total score in males compared to females. The effects of age and education on the predicted FER total score are visualized with 95% confidence intervals. FER, facial emotion recognition.

**FIGURE 4**
Effects of sex, age, and education per country in symptomatic pathogenic variant carriers. *Note*: Dotted lines indicate a higher predicted FER total score in males compared to females. The effects of age and education on the predicted FER total score are visualized with 95% confidence intervals. FER, facial emotion recognition.

**FIGURE 5**
Neuroanatomical correlates of performance on the FER total score in individuals with bvFTD. Results are corrected for family‐wise error (p < 0.05). bvFTD, behavioral variant of frontotemporal dementia; FER, facial emotion recognition.

See this image and copyright information in PMC

References

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Cross-country variance in facial emotion recognition in presymptomatic and symptomatic behavioral variant frontotemporal dementia: Insights from the GENFI and ReDLat consortia

Affiliations

Cross-country variance in facial emotion recognition in presymptomatic and symptomatic behavioral variant frontotemporal dementia: Insights from the GENFI and ReDLat consortia

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources