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    Rights statement: This is the author’s version of a work that was accepted for publication in Alzheimer's & Dementia. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Alzheimer's & Dementia, 14, 9, 2018 DOI: 10.1016/j.jalz.2018.04.005

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

Research output: Contribution to journalJournal article

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  • 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
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<mark>Journal publication date</mark>09/2018
<mark>Journal</mark>Alzheimer's and Dementia
Issue number9
Volume14
Number of pages11
Pages (from-to)1137-1147
Publication statusPublished
Early online date18/05/18
Original languageEnglish

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.

Bibliographic note

This is the author’s version of a work that was accepted for publication in Alzheimer's & Dementia. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Alzheimer's & Dementia, 14, 9, 2018 DOI: 10.1016/j.jalz.2018.04.005