Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive Impairment Subtypes and Interaction with APOE ɛ4 Genotype
Year: 2016
Type: article
Abstract: We examined cortical amyloid-β (Aβ) levels and interactions with apolipoprotein (APOE) ɛ4 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, and 34% of the NC group exceeded the amyloid positivity threshold. Finally, a group by APOE genotype interaction demonstrated that APOE ɛ4 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 Aβ 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 Aβ accumulation may occur earlier in APOE ɛ4 carriers compared to non-carriers.
Source: Journal of Alzheimer s Disease
DOI: 10.3233/jad-150900
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, U.S. Department of Veterans Affairs, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, F. Hoffmann-La Roche, Medpace, Meso Scale Diagnostics, Synarc, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, Eisai, Servier, IXICO, National Institutes of Health, Genentech, University of California, San Diego, Canadian Institutes of Health Research, National Institute on Aging
Awards: G1012222616, G104586243, G1554142629, G1593117279, G1650819308, G2100670906, G2152643862, G2189010064, G2340207221, G2409989180, G2423387114, G2522063444, G2835601961, G29951154, Statistically Determined MCI Subtypes: Genetics, Biomarkers and Outcomes, G3131374986, Vascular Reserve and Protective Mechanisms in Aging and Alzheimer’s Dementia Risk, G3216574877, UCSD Alzheimer's Disease Research Center P50, G3553156159, G3710456697, G3752451908, G3870774570, G3908963977, G3966393351, G43180419, G4501223628, G4800177743, Cognitive Abilities of At-Risk Elderly for Dementia, G497807829, G5207404921, G5209990037, G528601746, G5365730499, G5654639750, Alzheimer's Disease Neuroimaging Initiative, G5740349702, G613619302, G6173816828, G6210868510, G6371410416, G6412110892, G6447063303, G6719828067, G6792506723, G6899163935, G6948409098, Alzheimer Disease Research Center, G72415811, G7298697282, G764699806, G7799614282, G781725486, G8228018387, G8281378126, G839208290, G8636843673, G8852128998, G8895907669, G8897063270, Neuroimaging and Risk Factor Correlates in Aging and MCI, G8957659042, G9000039018, G9000122335
OpenAlex ID: W2325401428