Association of apolipoprotein E variation with cognitive impairment across multiple neurodegenerative diagnoses

Allison A Dilliott; Kelly M Sunderland; Paula M McLaughlin; Angela C Roberts; Emily C Evans; Agessandro Abrahao; Malcolm A Binns; Sandra E Black; Michael Borrie; Leanne K Casaubon; Dar Dowlatshahi; Elizabeth Finger; Corinne E Fischer; Andrew Frank; Morris Freedman; David Grimes; Ayman Hassan; Mandar Jog; Sanjeev Kumar; Donna Kwan; Anthony E Lang; Jennifer Mandzia; Connie Marras; Mario Masellis; Adam D McIntyre; Stephen Pasternak; Bruce G Pollock; Tarek K Rajji; John F Robinson; Ekaterina Rogaeva; Demetrios J Sahlas; Gustavo Saposnik; Christine Sato; Dallas Seitz; Christen Shoesmith; Thomas Steeves; Stephen C Strother; Richard H Swartz; Brian Tan; David Tang-Wai; Maria C Tartaglia; Angela K Troyer; John Turnbull; Lorne Zinman; ONDRI Investigators; Robert A Hegele

doi:10.1016/j.neurobiolaging.2021.04.011

Association of apolipoprotein E variation with cognitive impairment across multiple neurodegenerative diagnoses

Neurobiol Aging. 2021 Sep:105:378.e1-378.e9. doi: 10.1016/j.neurobiolaging.2021.04.011. Epub 2021 Apr 24.

Authors

Allison A Dilliott¹, Kelly M Sunderland², Paula M McLaughlin³, Angela C Roberts⁴, Emily C Evans⁵, Agessandro Abrahao⁶, Malcolm A Binns⁷, Sandra E Black⁸, Michael Borrie⁹, Leanne K Casaubon¹⁰, Dar Dowlatshahi¹¹, Elizabeth Finger¹², Corinne E Fischer¹³, Andrew Frank¹⁴, Morris Freedman¹⁵, David Grimes¹⁶, Ayman Hassan¹⁷, Mandar Jog¹⁸, Sanjeev Kumar¹⁹, Donna Kwan²⁰, Anthony E Lang²¹, Jennifer Mandzia²², Connie Marras²¹, Mario Masellis²³, Adam D McIntyre²⁴, Stephen Pasternak²⁵, Bruce G Pollock¹⁹, Tarek K Rajji²⁶, John F Robinson²⁴, Ekaterina Rogaeva²⁷, Demetrios J Sahlas²⁸, Gustavo Saposnik²⁹, Christine Sato²⁷, Dallas Seitz³⁰, Christen Shoesmith³¹, Thomas Steeves³², Stephen C Strother³³, Richard H Swartz⁸, Brian Tan², David Tang-Wai³⁴, Maria C Tartaglia²⁷, Angela K Troyer³⁵, John Turnbull²⁸, Lorne Zinman⁶; ONDRI Investigators; Robert A Hegele³⁶

Affiliations

¹ Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address: adilliot@uwo.ca.
² Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
³ Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada; Nova Scotia Health Authority & Dalhousie University, Halifax, Nova Scotia, Canada.
⁴ Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL, USA; School of Communication Sciences and Disorders, Elborn College, Western University, London, Ontario, Canada.
⁵ Department of Medicine, University of Toronto, Mississauga, Ontario, Canada.
⁶ Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Ontario, Canada.
⁷ Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Ontario, Canada; LCCampbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program Sunnybrook Health Sciences Research Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
⁹ St. Joseph's Health Care Centre, London, Ontario, Canada; Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
¹⁰ Department of Medicine, University of Toronto, Mississauga, Ontario, Canada; University Health Network Stroke Program, Toronto Western Hospital, Toronto, Ontario, Canada.
¹¹ Nova Scotia Health Authority & Dalhousie University, Halifax, Nova Scotia, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
¹² Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada.
¹³ Keenan Research Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
¹⁴ Nova Scotia Health Authority & Dalhousie University, Halifax, Nova Scotia, Canada; Bruyère Research Institute, Ottawa, Ontario, Canada.
¹⁵ Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada; Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Baycrest Health Sciences, Toronto, Ontario, Canada.
¹⁶ Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
¹⁷ Thunder Bay Regional Health Research Institute, Thunder Bay, Ontario, Canada.
¹⁸ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; London Health Sciences Centre, London, Ontario, Canada.
¹⁹ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
²⁰ Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
²¹ Department of Medicine, University of Toronto, Mississauga, Ontario, Canada; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, Ontario, Canada.
²² Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
²³ Department of Medicine, University of Toronto, Mississauga, Ontario, Canada; Cognitive & Movement Disorders Clinic and L.C. Campbell Cognitive Neurology Research Unit, Hurvitz Brain Science Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
²⁴ Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
²⁵ Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Cognitive Neurology and Alzheimer's Disease Research Centre, Parkwood Institute, St. Joseph's Health Care, London, Ontario, Canada.
²⁶ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
²⁷ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
²⁸ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
²⁹ Department of Medicine, University of Toronto, Mississauga, Ontario, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Clinical Outcomes and Decision Neuroscience Unit, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
³⁰ Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
³¹ London Health Sciences Centre, London, Ontario, Canada.
³² Division of Neurology, St. Michael's Hospital, Toronto, Ontario, Canada.
³³ Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
³⁴ Department of Medicine, University of Toronto, Mississauga, Ontario, Canada; Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada; University Health Network Memory Clinic, Toronto Western Hospital, Toronto, Ontario, Canada.
³⁵ Department of Psychology, University of Toronto, Toronto, Ontario, Canada; Neuropsychology and Cognitive Health Program, Baycrest Health Sciences, Toronto, Ontario, Canada.
³⁶ Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

PMID: 34039480
DOI: 10.1016/j.neurobiolaging.2021.04.011

Abstract

For many years there has been uncertainty regarding how apolipoprotein E (APOE) E2 and E4 variants may influence overlapping features of neurodegeneration, such as cognitive impairment. We aimed to identify whether the APOE variants are associated with cognitive function across various neurodegenerative and cerebrovascular diagnoses (n = 513). Utilizing a comprehensive neuropsychology battery, multivariate multiple regression was used to assess the influence of APOE carrier status and disease cohort on performance across five cognitive domains. Irrespective of disease cohort, E4 carriers had significantly lower performance in verbal memory and visuospatial domains than those with E3/3, while E2 carriers' cognitive performance was not significantly different. However, E2 carriers with frontotemporal dementia (FTD) performed significantly worse than those with E3/3 in the attention/working memory, executive function, and visuospatial domains. Our results highlight that the influence of APOE variation on cognition is complex, in some cases varying based on diagnosis and possibly underlying disease pathology.

Keywords: APOE; Cognitive impairment; E2; E4; Neurodegenerative disease; Neuropsychology.

Publication types

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

MeSH terms

Aged
Apolipoprotein E2 / genetics*
Apolipoprotein E4 / genetics*
Attention
Cognition*
Cognitive Dysfunction / diagnosis*
Cognitive Dysfunction / genetics*
Cognitive Dysfunction / psychology
Cohort Studies
Executive Function
Female
Genetic Association Studies*
Genetic Variation / genetics*
Heterozygote
Humans
Male
Memory, Short-Term
Middle Aged
Neurodegenerative Diseases / complications*
Neurodegenerative Diseases / psychology
Neuropsychological Tests

Substances

Apolipoprotein E2
Apolipoprotein E4

Grants and funding

CIHR/Canada