Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study

Ryota Sakurai; Frederico Pieruccini-Faria; Benjamin Cornish; Julia Fraser; Malcolm A Binns; Derek Beaton; Allison Ann Dilliott; Donna Kwan; Joel Ramirez; Brian Tan; Christopher J M Scott; Kelly M Sunderland; Carmela Tartaglia; Elizabeth Finger; Lorne Zinman; Morris Freedman; Paula M McLaughlin; Richard H Swartz; Sean Symons; Anthony E Lang; Robert Bartha; Sandra E Black; Mario Masellis; Robert A Hegele; William McIlroy; ONDRI Investigators; Manuel Montero-Odasso

doi:10.1002/alz.13740

Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study

Alzheimers Dement. 2024 Apr;20(4):2968-2979. doi: 10.1002/alz.13740. Epub 2024 Mar 12.

Authors

Ryota Sakurai^{1

2}, Frederico Pieruccini-Faria^{2

3}, Benjamin Cornish⁴, Julia Fraser⁴, Malcolm A Binns⁵, Derek Beaton⁶, Allison Ann Dilliott⁷, Donna Kwan⁸, Joel Ramirez⁹, Brian Tan⁵, Christopher J M Scott⁵, Kelly M Sunderland⁵, Carmela Tartaglia^{10

11}, Elizabeth Finger¹², Lorne Zinman^{13

14}, Morris Freedman^{5

14

15}, Paula M McLaughlin¹⁶, Richard H Swartz^{13

14}, Sean Symons⁹, Anthony E Lang¹⁷, Robert Bartha¹⁸, Sandra E Black⁹, Mario Masellis⁹, Robert A Hegele^{19

20}, William McIlroy²¹; ONDRI Investigators¹; Manuel Montero-Odasso^{2

22

23}

Affiliations

¹ Research Team for Social Participation and Healthy Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi-ku, Tokyo, Japan.
² Gait & Brain Lab, St. Joseph' Health Care London, Lawson Health Research, Western University, Division of Geriatric Medicine, London, Ontario, Canada.
³ Department of Medicine, Division of Geriatric Medicine, Parkwood Hospital, Western University, Parkwood Institute, London, Ontario, Canada.
⁴ Neuroscience, Mobility and Balance Lab, Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, Canada.
⁵ Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
⁶ Data Science and Advanced Analytics, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.
⁷ Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada.
⁸ Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
⁹ L.C. Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Program, Department of Medicine (Neurology), Sunnybrook Research Institute, Sunnybrook HSC, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Krembil Brain Institute, University Health Network Memory Clinic, Toronto Western Hospital, Toronto, Ontario, Canada.
¹¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
¹² Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
¹³ Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
¹⁴ Department of Medicine (Neurology), University of Toronto, Toronto, Ontario, Canada.
¹⁵ Division of Neurology, Baycrest Health Sciences, Toronto, Ontario, Canada.
¹⁶ Halifax Clinical Psychology Residency Program, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada.
¹⁷ Division of Neurology, Department of Medicine, Edmond J Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
¹⁸ Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, London, Ontario, Canada.
¹⁹ Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
²⁰ Robarts Research Institute, Western University, London, Ontario, Canada.
²¹ Neuroscience, Mobility and Balance Laboratory, Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, Canada.
²² Gait and Brain Lab, Division of Geriatric Medicine, and Lawson Health Research Institute, Parkwood Institute, Western University, London, Ontario, Canada.
²³ Division of Geriatric Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, Parkwood Institute, London, Ontario, Canada.

Abstract

Introduction: Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases.

Methods: Gait speed, APOE E4, cognition, and neuroimaging were assessed in 480 older adults with neurodegeneration. Participants were grouped by APOE E4 presence and slow gait. Mediation analyses were conducted to determine if brain structures could explain the link between these factors and cognitive performance.

Results: APOE E4 carriers with slow gait had the lowest global cognitive performance and smaller gray matter volumes compared to non-APOE E4 carriers with normal gait. Coexistence of APOE E4 and slow gait best predicted global and domain-specific poorer cognitive performances, mediated by smaller gray matter volume.

Discussion: Gait slowness in APOE E4 carriers with neurodegenerative diseases may indicate extensive gray matter changes associated with poor cognition.

Highlights: APOE E4 and slow gait are risk factors for cognitive decline in neurodegenerative diseases. Slow gait and smaller gray matter volumes are associated, independently of APOE E4. Worse cognition in APOE E4 carriers with slow gait is explained by smaller GM volume. Gait slowness in APOE E4 carriers indicates poorer cognition-related brain changes.

Keywords: APOE E4; cognition; gait; gray matter volume; neurodegenerative diseases.

MeSH terms

Aged
Apolipoprotein E4* / genetics
Apolipoproteins E / genetics
Cognition
Gait
Genotype
Humans
Neurodegenerative Diseases* / genetics

Substances

Apolipoprotein E4
Apolipoproteins E

Abstract

MeSH terms

Substances

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