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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Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - APOE-ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies
AU - Saeed, Usman
AU - Mirza, Saira S.
AU - MacIntosh, Bradley J.
AU - Herrmann, Nathan
AU - Keith, Julia
AU - Ramirez, Joel
AU - Nestor, Sean M.
AU - Yu, Qinggang
AU - Knight, Jo
AU - Swardfager, Walter
AU - Potkin, Steven G.
AU - Rogaeva, Ekaterina
AU - George-Hyslop, Peter St.
AU - Black, Sandra E.
AU - Masellis, Mario
N1 - 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
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
KW - APOE
KW - MRI
KW - Hippocampus
KW - Alzheimer's disease
KW - Dementia with Lewy bodies
KW - Learning
KW - Memory
KW - Endophenotype
U2 - 10.1016/j.jalz.2018.04.005
DO - 10.1016/j.jalz.2018.04.005
M3 - Journal article
VL - 14
SP - 1137
EP - 1147
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 9
ER -