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Journal article
Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive Impairment Subtypes and Interaction with APOE epsilon 4 Genotype
Journal of Alzheimer's disease, v 52(3), pp 849-861
01 Jan 2016
PMID: 27031472
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We examined cortical amyloid-beta (A beta) levels and interactions with apolipoprotein (APOE) epsilon 4 genotype status across empirically-derived mild cognitive impairment (MCI) subgroups and cognitively normal older adults. Participants were 583 ADNI participants (444 MCI, 139 normal controls [NC]) with baseline florbetapir positron emission tomography (PET) amyloid imaging and neuropsychological testing. Of those with ADNI-defined MCI, a previous cluster analysis [1] classified 51% (n = 227) of the current sample as amnestic MCI, 8% (n = 37) as dysexecutive/mixed MCI, and 41% (n = 180) as cluster-derived normal (cognitively normal). Results demonstrated that the dysexecutive/mixed and amnestic MCI groups showed significantly greater levels of amyloid relative to the cluster-derived normal and NC groups who did not differ from each other. Additionally, 78% of the dysexecutive/mixed, 63% of the amnestic MCI, 42% of the cluster-derived normal, and34% of theNC group exceeded the amyloid positivity threshold. Finally, a group by APOE genotype interaction demonstrated that APOE epsilon 4 carriers within the amnestic MCI, cluster-derived normal, and NC groups showed significantly greater amyloid accumulation compared to non-carriers of their respective group. Such an interaction was not revealed within the dysexecutive/mixed MCI group which was characterized by both greater cognitive impairment and amyloid accumulation compared to the other participant groups. Our results from the ADNI cohort show considerable heterogeneity in A beta across all groups studied, even within a group of robust NC participants. Findings suggest that conventional criteria for MCI may be susceptible to false positive diagnostic errors, and that onset of A beta accumulation may occur earlier in APOE epsilon 4 carriers compared to non-carriers.
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Details
- Title
- Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive Impairment Subtypes and Interaction with APOE epsilon 4 Genotype
- Creators
- Katherine J. Bangen - VA San Diego Healthcare SystemAlexandra L. Clark - VA San Diego Healthcare SystemMadeline Werhane - San Diego State UniversityEmily C. Edmonds - VA San Diego Healthcare SystemDaniel A. Nation - Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USANicole Evangelista - VA San Diego Healthcare SystemMark W. Bondi - Vet Affairs San Diego Healthcare Syst, San Diego, CA USALisa Delano-Wood - Vet Affairs San Diego Healthcare Syst, San Diego, CA USA
- Publication Details
- Journal of Alzheimer's disease, v 52(3), pp 849-861
- Publisher
- IOS Press
- Number of pages
- 13
- Grant note
- R01 AG012674; K24 AG026431 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA BioClinica, Inc. National Institute of Biomedical Imaging and Bioengineering; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) Eli Lilly and Company; Eli Lilly Fujirebio Araclon Biotech GE Healthcare; General Electric Meso Scale Diagnostics, LLC. F. Hoffmann-La Roche Ltd; Hoffmann-La Roche EuroImmun Johnson & Johnson Pharmaceutical Research & Development LLC.; Johnson & Johnson; Johnson & Johnson USA U01 AG024904 / Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Merck Co., Inc.; Merck & Company Piramal Imaging Servier Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) NeuroRx Research Takeda Pharmaceutical Company; Takeda Pharmaceutical Company Ltd Bristol-Myers Squibb Company; Bristol-Myers Squibb Eisai Inc.; Eisai Co Ltd Synarc Inc. Alzheimer's Association IXICO Ltd. 1IK2CX000938 / VA Clinical Science Research Development Biogen Idec Inc.; Biogen Medpace, Inc. Pfizer Inc.; Pfizer Janssen Alzheimer Immunotherapy Research & Development, LLC. Neurotrack Technologies National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Elan Pharmaceuticals, Inc. Alzheimer's Drug Discovery Foundation Novartis Pharmaceuticals Corporation; Novartis W81XWH-12-2-0012 / DOD ADNI (Department of Defense NIRG-13-281806 / Alzheimer's Association Genentech, Inc.; Roche Holding; Genentech
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurology
- Web of Science ID
- WOS:000377137500008
- Scopus ID
- 2-s2.0-84971553893
- Other Identifier
- 991021880112804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences