期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 52, 期 3, 页码 849-861出版社
IOS PRESS
DOI: 10.3233/JAD-150900
关键词
Amyloid; apolipoprotein E; APOE; biomarkers; florbetapir; mild cognitive impairment; neuroimaging; neuropsychology; PET; positron emission tomography
资金
- VA Clinical Science Research Development [1IK2CX000938]
- NIH [R01 AG012674, K24 AG026431]
- Alzheimer's Association [NIRG-13-281806]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Company
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Medpace, Inc.
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Synarc Inc.
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- NATIONAL INSTITUTE ON AGING [R21AG055034, P50AG005131, U01AG024904, R01AG012674, K24AG026431, P50AG005142] Funding Source: NIH RePORTER
- Veterans Affairs [IK2CX000938] Funding Source: NIH RePORTER
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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