Clinical Psychopharmacology and Neuroscience Papers in Press available online.

Associations between education years and resting-state functional connectivity modulated by APOE ε4 carrier status in cognitively normal older adults
Dong Woo Kang 1,*, Jiwon Kim 1, Sunghwan Kim 2, Yoo Hyun Um 3, Sheng-Min Wang 2, Regina EY Kim 4, Yeong Sim Choe 4, Jiyeon Lee 4, Donghyeon Kim 4, Hyun Kook Lim 2,4, Chang Uk Lee 1
1Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 2Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 3Department of Psychiatry, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea , 4Research Institute, NEUROPHET Inc.; Seoul 06247, Republic of Korea
Objective: Cognitive reserve has emerged as a concept to explain the variable expression of clinical symptoms in the pathology of Alzheimer's disease (AD). The association between years of education, a proxy of cognitive reserve, and resting-state functional connectivity (rFC), a representative intermediate phenotype, has not been explored in the preclinical phase, considering risk factors for AD. We aimed to evaluate whether the relationship between years of education and rFC in cognitively preserved older adults differs depending on Aβ deposition and APOE ε4 carrier status as effect modifiers.
Methods: A total of 121 participants underwent functional MRI, [18F] flutemetamol PET-CT, APOE genotyping, and a neuropsychological battery. Potential interactions between years of education and AD risk factors for rFC of AD-vulnerable neural networks were assessed with whole-brain voxel-wise analysis.
Results: We found a significant education years-by-APOE ε4 carrier status interaction for the rFC from the seed region of the central executive (CEN) and dorsal attention networks. Moreover, there was a significant interaction of rFC between right superior occipital gyrus and the CEN seed region by APOE ε4 carrier status for memory performances and overall cognitive function.
Conclusions: In preclinical APOE ε4 carriers, higher years of education were associated with higher rFC of the AD vulnerable network, but this contributed to lower cognitive function. These results contribute to a deeper understanding of the impact of cognitive reserve on sensitive functional intermediate phenotypic markers in the preclinical phase of AD.
Accepted Manuscript [Submitted on 2023-07-12, Accepted on 2023-09-26]