Volume 18, Issue 11 p. 2272-2282
FEATURED ARTICLE

Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer's disease carriers and non-carriers: Baseline findings from the API ADAD Colombia Trial

Clara Vila-Castelar

Clara Vila-Castelar

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Search for more papers by this author
Pierre N. Tariot

Pierre N. Tariot

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Kaycee M. Sink

Kaycee M. Sink

Genentech Inc., South San Francisco, California, USA

Search for more papers by this author
David Clayton

David Clayton

Genentech Inc., South San Francisco, California, USA

Search for more papers by this author
Jessica B. Langbaum

Jessica B. Langbaum

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Ronald G. Thomas

Ronald G. Thomas

University of California, San Diego, California, USA

Search for more papers by this author
Yinghua Chen

Yinghua Chen

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Yi Su

Yi Su

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Kewei Chen

Kewei Chen

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Nan Hu

Nan Hu

Genentech Inc., South San Francisco, California, USA

Search for more papers by this author
Margarita Giraldo-Chica

Margarita Giraldo-Chica

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Carlos Tobón

Carlos Tobón

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Natalia Acosta-Baena

Natalia Acosta-Baena

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Ernesto Luna

Ernesto Luna

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Marisol Londoño

Marisol Londoño

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Paula Ospina

Paula Ospina

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Victoria Tirado

Victoria Tirado

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Claudia Muñoz

Claudia Muñoz

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Eliana Henao

Eliana Henao

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Yamile Bocanegra

Yamile Bocanegra

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Sergio Alvarez

Sergio Alvarez

Hospital Pablo Tobon Uribe, Medellin, CO, Colombia

Search for more papers by this author
Silvia Rios-Romenets

Silvia Rios-Romenets

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Valentina Ghisays

Valentina Ghisays

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Dhruman Goradia

Dhruman Goradia

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Wendy Lee

Wendy Lee

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Ji Luo

Ji Luo

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Michael H. Malek-Ahmadi

Michael H. Malek-Ahmadi

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Hillary D. Protas

Hillary D. Protas

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Francisco Lopera

Francisco Lopera

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, CO, Colombia

Search for more papers by this author
Eric M. Reiman

Eric M. Reiman

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
Yakeel T. Quiroz

Corresponding Author

Yakeel T. Quiroz

Correspondence

Yakeel T. Quiroz, Associate Professor, Harvard Medical School, Departments of Psychiatry and Neurology, Massachusetts General Hospital, 39 1st Avenue, Suite 101, Charlestown, MA 02129, USA.

Email: [email protected]

Search for more papers by this author
the API ADAD Colombia Trial Group

the API ADAD Colombia Trial Group

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Banner Alzheimer's Institute, Phoenix, Arizona, USA

Search for more papers by this author
First published: 01 February 2022
Citations: 7

Francisco Lopera, Eric M. Reiman, and Yakeel T. Quiroz are co-senior authors.

Declarations of interest: please see details in Acknowledgements/Conflicts/Funding Source section.

Abstract

Introduction

Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers.

Methods

We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing.

Results

Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory.

Discussion

Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience.

CONFLICTS OF INTEREST

Dr. Vila-Castelar receives funding from the Alzheimer's Association (2019-AARF-644631). Dr. Tariot reports receiving grants from the National Institute of Aging (RF1 AG041705-01A1, R01 AG055444, 1R01AG058468), and Genentech/Roche; other research support from the State of Arizona (Arizona Alzheimer's Consortium), Banner Alzheimer's Foundation, FBRI, GHR, and the Nomis Foundation, consultant fees from Acadia, AbbVie, AC Immune, and T3D; consulting fees and research support from Lilly, Lundbeck, Merck & Co., and Roche; research support only from Avid, Biogen, Genentech, and Novartis; and stocks in Adamas Pharmaceuticals. Dr. Langbaum reports grants from the NIA (1R01AG063954; 1R01AG058468) and the State of Arizona (Arizona Alzheimer's Consortium) during the course of the study. She has received consulting fees from Alector. Drs. Sink, Clayton, Hu are full-time employees of Genentech, a member of the Roche group, and hold stock in Roche. Drs. Giraldo-Chica, Tobón, Acosta-Baena, Luna, Bocanegra, Rios-Romenets and Lopera, and Mses. Londoño, Ospina, Tirado, Muñoz, Henao report participation in other projects financed by the National Institutes of Health, Comité para el Desarrollo de la Investigación (CODI- UdeA) and COLCIENCIAS. Dr. Reiman reports grants from the NIA (R01 AG031581, P30 AG19610), Banner Alzheimer's Foundation, and the NOMIS Foundation during the course of the study. He has received consulting fees from Alkahest, Alzheon, Aural Analytics, Biogen, Denali, Green Valley, Pfizer, Roche (Expenses Only), United Neuroscience, and Zinfandel Pharma; research support from Avid/Lilly, Genentech/Roche, and Novartis/Amgen, the National Institute on Aging, the National Institute of Neurologic Disorders, Banner Alzheimer's Foundation, Alzheimer's Association, GHR Foundation, FBRI, NOMIS Foundation, Flinn Foundation, and the State of Arizona. Dr. Quiroz reports grants from the NIH Office of the Director (DP5OD019833), the NIH NIA (R01 AG054671), the Alzheimer's Association, and Massachusetts General Hospital ECOR. The authors report no further potential conflicts of interest.