Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research

Karen Nuytemans^{1

2}, Sanne Franzen³, Iris J Broce^{4

5}, Paulo Caramelli⁶, Ratnavalli Ellajosyula^{7

8}, Elizabeth Finger^{9

10

11}, Veer Gupta¹², Vivek Gupta¹³, Ignacio Illán-Gala^{14

15}, Samantha M Loi^{16

17}, Darby Morhardt¹⁸, Yolande Pijnenburg^{19

20}, Katya Rascovsky²¹, Monique M Williams²², Jennifer S Yokoyama^{5

23}, Juliana Acosta-Uribe^{24

25}, Rufus Akinyemi²⁶, Suvarna Alladi²⁷, Biniyam A Ayele^{1

28}, Yavuz Ayhan^{29

30}, Renelle Bourdage^{3

31}, Sheila Castro-Suarez^{32

33}, Leonardo Cruz de Souza^{6

34}, Penny Dacks³⁵, Sterre C M de Boer^{19

20

36}, Jessica de Leon⁵, Shana Dodge³⁵, Stephanie Grasso³⁷, Nupur Ghoshal³⁸, Vidyulata Kamath³⁹, Fiona Kumfor³⁶, Jordi A Matias-Guiu⁴⁰, Pauline Narme³¹, T Rune Nielsen⁴¹, Daniel Okhuevbie^{42

43}, Stefanie Piña-Escudero^{5

33}, Ramiro Ruiz-Garcia^{9

11

44}, Brigid Ryan⁴⁵, Marta Scarioni⁴⁶, Andrea Slachevsky^{47

48

49

50}, Aida Suarez-Gonzalez⁵¹, Boon Lead Tee^{5

33

52}, Elena Tsoy^{5

33}, Hulya Ulugut^{5

19

20}, Chiadi U Onyike³⁹, Ganesh M Babulal^{53

54

55

56}; ISTAART Frontotemporal Dementia and Related Disorders PIA, ISTAART Diversity and Disparities PIA

Affiliations

¹ John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
² Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
³ Department of Neurology and Alzheimer Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁴ Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
⁵ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
⁶ Behavioral and Cognitive Neurology Unit, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
⁷ Manipal Hospitals, Bangalore and Annasawmy Mudaliar Hospital, Bangalore, India.
⁸ Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India.
⁹ Parkwood Institute Research, London, London, Ontario, Canada.
¹⁰ Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
¹¹ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
¹² IMPACT-The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
¹³ Macquarie Medical school, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, New South Wales, Australia.
¹⁴ Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁵ Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Monforte de Lemos, Madrid, Spain.
¹⁶ Neuropsychiatry, Royal Melbourne Hospital, Parkville, Victoria, Australia.
¹⁷ Department of Psychiatry, University of Melbourne, Parkville, Victoria, Australia.
¹⁸ Mesulam Center for Cognitive Neurology and Alzheimer's Disease and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁹ Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, North Holland, The Netherlands.
²⁰ Amsterdam Neuroscience, Neurodegeneration, Amsterdam UMC, Amsterdam, North Holland, The Netherlands.
²¹ Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
²² Oak Street Health - North City, St. Louis, Missouri, USA.
²³ Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
²⁴ Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Antioquia, Colombia.
²⁵ Neuroscience Research institute and Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, California, USA.
²⁶ Neuroscience and Ageing Research Unit, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria.
²⁷ Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
²⁸ Department of Neurology, CHS, Addis Ababa University, Addis Ababa, Ethiopia.
²⁹ Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sıhhiye/Altindag, Ankara, Turkey.
³⁰ Faculty of Medicine, Department of Psychiatry, Hacettepe University, Sıhhiye/Altindag, Ankara, Turkey.
³¹ Laboratoire Mémoire Cerveau et Cognition (UR 7536), Institut de Psychologie, Université Paris Cité, Boulogne-Billancourt, France.
³² CBI en Demencias y Enfermedades Desmielinizantes del Sistema Nervioso, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
³³ Global Brain Health Institute, University of California, San Francisco, San Francisco, California, USA.
³⁴ Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
³⁵ The Association for Frontotemporal Degeneration, King of Prussia, Pennsylvania, USA.
³⁶ Brain & Mind Centre and the School of Psychology, The University of Sydney, Camperdown, New South Wales, Australia.
³⁷ Speech, Language and Hearing Sciences, The University of Texas at Austin, Austin, Texas, USA.
³⁸ Depts. of Neurology and Psychiatry, Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA.
³⁹ Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴⁰ Department of Neurology, Hospital Clinico San Carlos, San Carlos Institute for Health Research (IdiSSC), Universidad Complutense, Madrid, Spain.
⁴¹ Danish Dementia Research Center, Copenhagen University Hospital, Rigshospitalet, and Department of Phychology, University of Copenhagen, Copenhagen, Denmark.
⁴² Department of Cell Biology and Genetics, University of Lagos, Tafawa Balewa, Lagos, Nigeria.
⁴³ Waisman Center, and Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁴⁴ National Institute of Neurology and Neurosurgery, Mexico City, Mexico.
⁴⁵ Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
⁴⁶ Department of Neurology, Ghent University Hospital, Ghent, Belgium.
⁴⁷ Geroscience Center for Brain Health and Metabolism (GERO), Ñuñoa Santiago, Santiago, Chile.
⁴⁸ Neuropsychology and Clinical Neuroscience Laboratory (LANNEC), Physiopathology Department - Institute of Biomedical Sciences (ICBM), Neurocience and East Neuroscience Departments, Faculty of Medicine, University of Chile, Independencia, Santiago, Chile.
⁴⁹ Memory and Neuropsychiatric Center (CMYN), Memory Unit, Neurology Department, Hospital del Salvador and Faculty of Medicine, University of Chile, Providencia, Santiago, Chile.
⁵⁰ Neurology and Psychiatry Department, Clínica Alemana-Universidad Desarrollo, Santiago, Chile.
⁵¹ Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.
⁵² Dyslexia Center, Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
⁵³ Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
⁵⁴ Institute of Public Health, Washington University in St. Louis, St. Louis, Missouri, USA.
⁵⁵ Department of Psychology, Faculty of Humanities, University of Johannesburg, Johannesburg, South Africa.
⁵⁶ Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington DC, USA.

PMID: 39535468
PMCID: PMC11667558
DOI: 10.1002/alz.14312

Review

Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research

Karen Nuytemans et al. Alzheimers Dement. 2024 Dec.

. 2024 Dec;20(12):9014-9036.

doi: 10.1002/alz.14312. Epub 2024 Nov 13.

Authors

Affiliations

¹ John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
² Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
³ Department of Neurology and Alzheimer Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁴ Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
⁵ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
⁶ Behavioral and Cognitive Neurology Unit, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
⁷ Manipal Hospitals, Bangalore and Annasawmy Mudaliar Hospital, Bangalore, India.
⁸ Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India.
⁹ Parkwood Institute Research, London, London, Ontario, Canada.
¹⁰ Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
¹¹ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
¹² IMPACT-The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
¹³ Macquarie Medical school, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, New South Wales, Australia.
¹⁴ Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁵ Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Monforte de Lemos, Madrid, Spain.
¹⁶ Neuropsychiatry, Royal Melbourne Hospital, Parkville, Victoria, Australia.
¹⁷ Department of Psychiatry, University of Melbourne, Parkville, Victoria, Australia.
¹⁸ Mesulam Center for Cognitive Neurology and Alzheimer's Disease and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁹ Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, North Holland, The Netherlands.
²⁰ Amsterdam Neuroscience, Neurodegeneration, Amsterdam UMC, Amsterdam, North Holland, The Netherlands.
²¹ Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
²² Oak Street Health - North City, St. Louis, Missouri, USA.
²³ Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
²⁴ Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Antioquia, Colombia.
²⁵ Neuroscience Research institute and Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, California, USA.
²⁶ Neuroscience and Ageing Research Unit, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria.
²⁷ Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
²⁸ Department of Neurology, CHS, Addis Ababa University, Addis Ababa, Ethiopia.
²⁹ Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sıhhiye/Altindag, Ankara, Turkey.
³⁰ Faculty of Medicine, Department of Psychiatry, Hacettepe University, Sıhhiye/Altindag, Ankara, Turkey.
³¹ Laboratoire Mémoire Cerveau et Cognition (UR 7536), Institut de Psychologie, Université Paris Cité, Boulogne-Billancourt, France.
³² CBI en Demencias y Enfermedades Desmielinizantes del Sistema Nervioso, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
³³ Global Brain Health Institute, University of California, San Francisco, San Francisco, California, USA.
³⁴ Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
³⁵ The Association for Frontotemporal Degeneration, King of Prussia, Pennsylvania, USA.
³⁶ Brain & Mind Centre and the School of Psychology, The University of Sydney, Camperdown, New South Wales, Australia.
³⁷ Speech, Language and Hearing Sciences, The University of Texas at Austin, Austin, Texas, USA.
³⁸ Depts. of Neurology and Psychiatry, Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA.
³⁹ Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴⁰ Department of Neurology, Hospital Clinico San Carlos, San Carlos Institute for Health Research (IdiSSC), Universidad Complutense, Madrid, Spain.
⁴¹ Danish Dementia Research Center, Copenhagen University Hospital, Rigshospitalet, and Department of Phychology, University of Copenhagen, Copenhagen, Denmark.
⁴² Department of Cell Biology and Genetics, University of Lagos, Tafawa Balewa, Lagos, Nigeria.
⁴³ Waisman Center, and Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁴⁴ National Institute of Neurology and Neurosurgery, Mexico City, Mexico.
⁴⁵ Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
⁴⁶ Department of Neurology, Ghent University Hospital, Ghent, Belgium.
⁴⁷ Geroscience Center for Brain Health and Metabolism (GERO), Ñuñoa Santiago, Santiago, Chile.
⁴⁸ Neuropsychology and Clinical Neuroscience Laboratory (LANNEC), Physiopathology Department - Institute of Biomedical Sciences (ICBM), Neurocience and East Neuroscience Departments, Faculty of Medicine, University of Chile, Independencia, Santiago, Chile.
⁴⁹ Memory and Neuropsychiatric Center (CMYN), Memory Unit, Neurology Department, Hospital del Salvador and Faculty of Medicine, University of Chile, Providencia, Santiago, Chile.
⁵⁰ Neurology and Psychiatry Department, Clínica Alemana-Universidad Desarrollo, Santiago, Chile.
⁵¹ Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.
⁵² Dyslexia Center, Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
⁵³ Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
⁵⁴ Institute of Public Health, Washington University in St. Louis, St. Louis, Missouri, USA.
⁵⁵ Department of Psychology, Faculty of Humanities, University of Johannesburg, Johannesburg, South Africa.
⁵⁶ Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington DC, USA.

PMID: 39535468
PMCID: PMC11667558
DOI: 10.1002/alz.14312

Abstract

Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure. This perspective paper was produced by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) and discusses the field's current status on the cross-cultural aspects of basic and translational research in FTD (including that focused on epidemiology, genetics, biomarkers, and treatment). It subsequently provides a summary of gaps and needs to address the disparities and advance global FTD biomedical research.

Keywords: biomarkers; cultural diversity; epidemiology; ethnicity; frontotemporal dementia; genetics; infrastructure.

PubMed Disclaimer

Conflict of interest statement

S.F. receives royalties on two neuropsychological tests (mVAT and FDT; Hogrefe). N.G. receives consulting fees from Blue Cross Blue Shield Association. C.U.O. receives consulting fees from Acadia Pharmaceuticals, Reata Pharmaceuticals, Otsuka Pharmaceuticals, Eli Lily and Company, Alexion Pharmaceuticals, Lykis Therapeutics, and Zeyra Therapeutics. All other authors report no conflicts of interest. Author disclosures are available in the supporting information.

Figures

**FIGURE 1**
Contributions of major genetic ancestries to large world populations and example population groups representing variability, on average. Blue = European ancestry, Orange = African ancestry, Gray = Amerindian (U.S.) ancestry, Yellow = South Asian ancestry, Purple = East Asian Ancestry, Pink = First Nations (Australia) ancestry, Green = Papua New Guinean ancestry.

See this image and copyright information in PMC

References

1. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134(Pt 9):2456‐2477. doi:10.1093/brain/awr179 - DOI - PMC - PubMed
1. Gorno‐Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006‐1014. doi:10.1212/WNL.0b013e31821103e6 - DOI - PMC - PubMed
1. Franzen S, Nuytemans K, Bourdage R, et al. Gaps in clinical research in frontotemporal dementia: a call for diversity and disparities‐focused research. Alzheimers Dement. 2023;19(12):5817‐5836. doi:10.1002/alz.13129 - DOI - PMC - PubMed
1. Onyike CU, Shinagawa S, Ellajosyula R. Frontotemporal dementia: a cross‐cultural perspective. Adv Exp Med Biol. 2021;1281:141‐150. doi:10.1007/978-3-030-51140-1_10 - DOI - PubMed
1. Onyike CU, Diehl‐Schmid J. The epidemiology of frontotemporal dementia. Int Rev Psychiatry. 2013;25(2):130‐137. doi:10.3109/09540261.2013.776523 - DOI - PMC - PubMed

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Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research

Affiliations

Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous