The Relationship of Brain Amyloid Load and APOE Status to Regional Cortical Thinning and Cognition in the ADNI Cohort

Article type: Research Article

Authors: Li, Chunfei^a | Loewenstein, David A.^{b; c; d} | Duara, Ranjan^{b; d; e} | Cabrerizo, Mercedes^a | Barker, Warren^{b; e} | Adjouadi, Malek^{a; e; *} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Center for Advanced Technology and Education, Department of Electrical and Computer Engineering, Florida International University, Miami, FL, USA | [b] Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA | [c] Center on Aging and Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA | [d] Departments of Neurology, University of Florida College of Medicine, Gainesville, FL, USA and Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA | [e] 1Florida ADRC (Florida Alzheimer’s Disease Research Center) at Gainesville, Miami Beach, Miami, FL, USA and Boca Raton, FL, USA

Correspondence: [*] Correspondence to: Malek Adjouadi, Center for Advanced Technology and Education, Department of Electrical and Computer Engineering, College of Engineering and Computing, Florida International University, 10555 W. Flagler Street. Miami, FL, 33174, USA. Tel.: +1 305 348 3019; 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 ADNI and/or provided data but did not participate in analysis or writing of this report. 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: Background:Both amyloid (Aβ) load and APOE4 allele are associated with neurodegenerative changes in Alzheimer’s disease (AD) prone regions and with risk for cognitive impairment. Objective:To evaluate the unique and independent contribution of APOE4 allele status (E4+∖E4–), Aβ status (Amy+∖Amy–), and combined APOE4 and Aβ status on regional cortical thickness (CoTh) and cognition among participants diagnosed as cognitively normal (CN, n = 251), early mild cognitive impairment (EMCI, n = 207), late mild cognitive impairment (LMCI, n = 196), and mild AD (n = 162) from the ADNI. Methods:A series of two-way ANCOVAs with post-hoc Tukey HSD tests, controlling independently for Aβ and APOE4 status and age were examined. Results:Among LMCI and AD participants, cortical thinning was widespread in association with Amy+ status, whereas in association with E4+ status only in the inferior temporal and medial orbito-frontal regions. Among CN and EMCI participants, E4+ status, but not Amy+ status, was independently associated with increased CoTh, especially in limbic regions [e.g., in the entorhinal cortex, CoTh was 0.123 mm greater (p = 0.002) among E4+ than E4–participants]. Among CN and EMCI, both E4+ and Amy+ status were independently associated with cognitive impairment, which was greatest among those with combined E4 + and Amy+ status. Conclusion:Decreased CoTh is independently associated with Amy+ status in many brain regions, but with E4+ status in very restricted number of brain regions. Among CN and EMCI participants, E4 + status is associated with increased CoTh, in medial and inferior temporal regions, although cognitive impairment at this state is independently associated with Amy+ and E4 + status. These findings imply a unique pathophysiological mechanism for E4 + status in AD and its progression.

Keywords: ADNI, Alzheimer’s disease, amyloid, APOE, cortical thinning, memory, mild cognitive impairment

DOI: 10.3233/JAD-170286

Journal: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1269-1282, 2017