Usman Saeed1, Saira S Mirza2, Bradley J MacIntosh3, Nathan Herrmann4, Julia Keith5, Joel Ramirez6, Sean M Nestor7, Qinggang Yu8, Jo Knight9, Walter Swardfager10, Steven G Potkin11, Ekaterina Rogaeva12, Peter St George-Hyslop13, Sandra E Black14, Mario Masellis15. 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.
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.
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.
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