title: Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive Impairment Subtypes and Interaction with APOE ɛ4 Genotype.
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.
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Bangen
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.|San Diego State University/University of California, San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Clark
authors.affiliation: San Diego State University/University of California, San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
authors.forename: Madeline
authors.initials: M
authors.lastname: Werhane
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Edmonds
authors.affiliation: Department of Psychology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nation
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Evangelista
authors.affiliation: Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Libon
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Bondi
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Delano-Wood
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D016000:Cluster Analysis; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D005026:Ethylene Glycols; D005189:False Positive Reactions; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; C545186:florbetapir
keywords: APOE; Amyloid; PET; apolipoprotein E; biomarkers; florbetapir; mild cognitive impairment; neuroimaging; neuropsychology; positron emission tomography