Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium

Jessica Gong; Katie Harris; Darren M Lipnicki; Erico Castro-Costa; Maria Fernanda Lima-Costa; Breno S Diniz; Shifu Xiao; Richard B Lipton; Mindy J Katz; Cuiling Wang; Pierre-Marie Preux; Maëlenn Guerchet; Antoine Gbessemehlan; Karen Ritchie; Marie-Laure Ancelin; Ingmar Skoog; Jenna Najar; Therese Rydberg Sterner; Nikolaos Scarmeas; Mary Yannakoulia; Mary H Kosmidis; Antonio Guaita; Elena Rolandi; Annalisa Davin; Oye Gureje; Stella Trompet; Jacobijn Gussekloo; Steffi Riedel-Heller; Alexander Pabst; Susanne Röhr; Suzana Shahar; Devinder Kaur Ajit Singh; Nurul Fatin Malek Rivan; Martin van Boxtel; Sebastian Köhler; Mary Ganguli; Chung-Chou Chang; Erin Jacobsen; Mary Haan; Ding Ding; Qianhua Zhao; Zhenxu Xiao; Kenji Narazaki; Tao Chen; Sanmei Chen; Tze Pin Ng; Xinyi Gwee; Katya Numbers; Karen A Mather; Marcia Scazufca; Antonio Lobo; Concepción De-la-Cámara; Elena Lobo; Perminder S Sachdev; Henry Brodaty; Maree L Hackett; Sanne A E Peters; Mark Woodward; Cohort Studies of Memory in an International Consortium (COSMIC)

doi:10.1002/alz.12962

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium

Alzheimers Dement. 2023 Aug;19(8):3365-3378. doi: 10.1002/alz.12962. Epub 2023 Feb 15.

Authors

Jessica Gong^{1

2}, Katie Harris¹, Darren M Lipnicki³, Erico Castro-Costa⁴, Maria Fernanda Lima-Costa⁴, Breno S Diniz⁵, Shifu Xiao⁶, Richard B Lipton⁷, Mindy J Katz⁷, Cuiling Wang⁸, Pierre-Marie Preux⁹, Maëlenn Guerchet⁹, Antoine Gbessemehlan⁹, Karen Ritchie¹⁰, Marie-Laure Ancelin¹⁰, Ingmar Skoog¹¹, Jenna Najar¹¹, Therese Rydberg Sterner¹¹, Nikolaos Scarmeas^{12

13}, Mary Yannakoulia¹⁴, Mary H Kosmidis¹⁵, Antonio Guaita¹⁶, Elena Rolandi^{16

17}, Annalisa Davin¹⁶, Oye Gureje¹⁸, Stella Trompet¹⁹, Jacobijn Gussekloo^{19

20}, Steffi Riedel-Heller²¹, Alexander Pabst²¹, Susanne Röhr²¹, Suzana Shahar²², Devinder Kaur Ajit Singh²², Nurul Fatin Malek Rivan²², Martin van Boxtel²³, Sebastian Köhler²³, Mary Ganguli²⁴, Chung-Chou Chang²⁴, Erin Jacobsen²⁴, Mary Haan²⁵, Ding Ding²⁶, Qianhua Zhao²⁶, Zhenxu Xiao²⁶, Kenji Narazaki²⁷, Tao Chen²⁸, Sanmei Chen²⁹, Tze Pin Ng³⁰, Xinyi Gwee³⁰, Katya Numbers³, Karen A Mather³, Marcia Scazufca³¹, Antonio Lobo^{32

33

34}, Concepción De-la-Cámara^{32

34}, Elena Lobo^{33

34

35}, Perminder S Sachdev³, Henry Brodaty³, Maree L Hackett^{1

36}, Sanne A E Peters^{1

2

37}, Mark Woodward^{1

2}; Cohort Studies of Memory in an International Consortium (COSMIC)

Affiliations

¹ The George Institute for Global Health, University of New South Wales, Sydney, Australia.
² The George Institute for Global Health, Imperial College London, London, UK.
³ Centre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
⁴ Center for Studies in Public Health and Aging Rene Rachou Institute, Oswaldo Cruz Foundation, Belo Horizonte, Brazil.
⁵ UConn Center on Aging, Department of Psychiatry, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA.
⁶ Department of Geriatric Psychiatry, Shanghai Mental Health Centre, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁷ Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.
⁸ Department of Epidemiology and Community Heath, Albert Einstein College of Medicine, Bronx, New York, USA.
⁹ Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of chronic diseases in tropical zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, Limoges, France.
¹⁰ INM Institute for Neurosciences of Montpellier, Univ Montpellier, INSERM, Montpellier, France.
¹¹ Department of Psychiatry and Neurochemistry, Center for Ageing and Health (Age Cap), University of Gothenburg, Gothenburg, Sweden.
¹² 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.
¹³ Department of Neurology, Columbia University, New York, New York, USA.
¹⁴ Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
¹⁵ Lab of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹⁶ Golgi Cenci Foundation, Abbiategrasso, Italy.
¹⁷ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
¹⁸ WHO Collaborating Centre for Research and Training in Mental Health, Neurosciences and Substance Abuse, Department of Psychiatry, University of Ibadan, Ibadan, Nigeria.
¹⁹ Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
²⁰ Department of Public Health and Primary Care, Leiden, the Netherlands.
²¹ Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany.
²² Centre for Healthy Ageing and Wellness, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
²³ Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
²⁴ Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
²⁵ Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
²⁶ Institute of Neurology, National Center for Neurological Disorders, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
²⁷ Center for Liberal Arts, Fukuoka Institute of Technology, Fukuoka, Japan.
²⁸ Sports and Health Research Center, Department of Physical Education, Tongji University, Shanghai, China.
²⁹ Global Health Nursing, Department of Health Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
³⁰ Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Queenstown, Singapore.
³¹ Instituto de Psiquiátria e LIM-23, Hospital da Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
³² Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain.
³³ Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.
³⁴ n°33 CIBERSAM, Madrid, Spain.
³⁵ Department of Public Health, Universidad de Zaragoza, Zaragoza, Spain.
³⁶ Faculty of Health and Wellbeing, University of Central Lancashire, Lancashire, UK.
³⁷ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Abstract

Introduction: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups.

Methods: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models.

Results: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs.

Discussion: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Keywords: data harmonization; dementia; diversity; risk factor; sex difference.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alcohol Drinking
Dementia* / epidemiology
Female
Humans
Male
Risk Factors
Sex Characteristics*
Sex Factors

Abstract

Publication types

MeSH terms

Grants and funding