APOE-ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies

Usman Saeed; Saira S Mirza; Bradley J MacIntosh; Nathan Herrmann; Julia Keith; Joel Ramirez; Sean M Nestor; Qinggang Yu; Jo Knight; Walter Swardfager; Steven G Potkin; Ekaterina Rogaeva; Peter St George-Hyslop; Sandra E Black; Mario Masellis

doi:10.1016/j.jalz.2018.04.005

APOE-ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies

Alzheimers Dement. 2018 Sep;14(9):1137-1147. doi: 10.1016/j.jalz.2018.04.005. Epub 2018 May 18.

Authors

Affiliations

¹ Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
² Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
³ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁴ Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁵ Department of Anatomical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁶ LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁷ LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁸ LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
⁹ Data Science Institute and Medical School, Lancaster University, Lancaster, UK.
¹⁰ LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
¹¹ Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
¹² Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
¹³ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada; Cambridge Institute for Medical Research, Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK.
¹⁴ Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
¹⁵ Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada. Electronic address: mario.masellis@sunnybrook.ca.

PMID: 29782824
DOI: 10.1016/j.jalz.2018.04.005

Abstract

Introduction: Although the apolipoprotein E ε4-allele (APOE-ε4) is a susceptibility factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), its relationship with imaging and cognitive measures across the AD/DLB spectrum remains unexplored.

Methods: We studied 298 patients (AD = 250, DLB = 48; 38 autopsy-confirmed; NCT01800214) using neuropsychological testing, volumetric magnetic resonance imaging, and APOE genotyping to investigate the association of APOE-ε4 with hippocampal volume and learning/memory phenotypes, irrespective of diagnosis.

Results: Across the AD/DLB spectrum: (1) hippocampal volumes were smaller with increasing APOE-ε4 dosage (no genotype × diagnosis interaction observed), (2) learning performance as assessed by total recall scores was associated with hippocampal volumes only among APOE-ε4 carriers, and (3) APOE-ε4 carriers performed worse on long-delay free word recall.

Discussion: These findings provide evidence that APOE-ε4 is linked to hippocampal atrophy and learning/memory phenotypes across the AD/DLB spectrum, which could be useful as biomarkers of disease progression in therapeutic trials of mixed disease.

Keywords: APOE; Alzheimer's disease; Dementia with Lewy bodies; Endophenotype; Hippocampus; Learning; MRI; Memory.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / genetics*
Alzheimer Disease / psychology
Apolipoprotein E4 / genetics*
Endophenotypes
Female
Genetic Predisposition to Disease
Heterozygote
Hippocampus / diagnostic imaging*
Hippocampus / pathology
Humans
Learning*
Lewy Body Disease / diagnostic imaging
Lewy Body Disease / genetics*
Lewy Body Disease / psychology
Magnetic Resonance Imaging
Male
Neuropsychological Tests
Organ Size

Substances

Apolipoprotein E4

Associated data

ClinicalTrials.gov/NCT01800214

Grants and funding

MOP13129/Canadian Institutes of Health Research/International