Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive Impairment Subtypes and Interaction with APOE ɛ4 Genotype

Article type: Research Article

Authors: Bangen, Katherine J.^{a; b; *} | Clark, Alexandra L.^{a; c} | Werhane, Madeline^c | Edmonds, Emily C.^{a; b} | Nation, Daniel A.^d | Evangelista, Nicole^{a; b} | Libon, David J.^e | Bondi, Mark W.^{a; b} | Delano-Wood, Lisa^{a; b} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Veterans Affairs San Diego Healthcare System, San Diego, CA, USA | [b] Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA | [c] San Diego State University/University of California, San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA | [d] Department of Psychology, University of Southern California, Los Angeles, CA, USA | [e] Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Katherine Bangen, PhD, 9500 Gilman Drive, Mail Code 151B, San Diego, CA 92093-9151, USA. Tel.: +1 858 552 8585/Ext: 5794; Fax: +1 858 642 6340; E-mail: [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of the ADNI and/or provided data but did not participate in analysis or writing of this article. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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.

Keywords: Amyloid, apolipoprotein E, APOE, biomarkers, florbetapir, mild cognitive impairment, neuroimaging, neuropsychology, PET, positron emission tomography

DOI: 10.3233/JAD-150900

Journal: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 849-861, 2016