Greater Regional Cortical Thickness is Associated with Selective Vulnerability to Atrophy in Alzheimer’s Disease, Independent of Amyloid Load and APOE Genotype

Article type: Research Article

Authors: Li, Chunfei^a | Duara, Ranjan^{b; c; d; e} | Loewenstein, David A.^{b; c; f} | Izquierdo, Walter^a | Cabrerizo, Mercedes^a | Barker, Warren^{b; c} | Adjouadi, Malek^{a; c; *} | and 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, FL, USA | [c] Florida Alzheimer’s Disease Research Center at Gainesville, Miami Beach, Miami, USA | [d] Department of Neurology, University of Florida College of Medicine, Gainesville, FL, USA | [e] Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA | [f] Center on Aging and Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, 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, 10555W. 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:Regional cortical thickness (rCTh) among cognitively normal (CN) adults (rCThCN) varies greatly between brain regions, as does the vulnerability to neurodegeneration. Objective:The goal of this study was to: 1) rank order rCThCN for various brain regions, and 2) explore their vulnerability to neurodegeneration in Alzheimer’s disease (AD) within these brain regions. Methods:The relationship between rCTh among the CN group (rCThCN) and the percent difference in CTh (% CThDiff) in each region between the CN group and AD patients was examined. Pearson correlation analysis was performed accounting for amyloid-β (Aβ) protein and APOE genotype using 210 age, gender, and APOE matched CN (n = 105, age range: 56–90) and AD (n = 105, age range: 56–90) ADNI participants. Results:Strong positive correlations were observed between rCThCN and % CThDiff accounting for Aβ deposition and APOE status. Regions, such as the entorhinal cortex, which had the greatest CTh in the CN state, were also the regions which had the greatest % CThDiff. Conclusions:Regions with the greatest CTh at the CN stage are found to aggregate in disease prone regions of AD, namely in the medial temporal lobe, including the temporal pole, ERC, parahippocampal gyrus, fusiform and the middle and inferior temporal gyrus. Although rCTh has been found to vary considerably across the different regions of the brain, our results indicate that regions with the greatest CTh at the CN stage are actually regions which have been found to be most vulnerable to neurodegeneration in AD.

Keywords: Alzheimer’s disease, amyloid-β , APOE, cortical atrophy, neuroimaging

DOI: 10.3233/JAD-180231

Journal: Journal of Alzheimer's Disease, vol. 69, no. 1, pp. 145-156, 2019