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Aberrant interhemispheric functional connectivity within default mode network and its relationships with neurocognitive features in cognitively normal APOE ε 4 elderly carriers

Published online by Cambridge University Press:  26 January 2017

Hanna Lu*
Department of Psychiatry, The Chinese University of Hong Kong, G/F Multicenter, Tai Po Hospital, Hong Kong SAR, China Department of Psychiatry, Guangzhou Brain Hospital, The Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Suk Ling Ma
Department of Psychiatry, The Chinese University of Hong Kong, G/F Multicenter, Tai Po Hospital, Hong Kong SAR, China
Savio Wai Ho Wong
Department of Special Education and Counselling, Hong Kong Institute of Education Center for Brain and Education, The Hong Kong Institute of Education, Hong Kong SAR, China
Cindy W. C. Tam
Department of Psychiatry, The Chinese University of Hong Kong, G/F Multicenter, Tai Po Hospital, Hong Kong SAR, China
Sheung-Tak Cheng
Department of Health and Physical Education, The Education University of Hong Kong, Hong Kong SAR, China
Sandra S. M. Chan
Department of Psychiatry, The Chinese University of Hong Kong, G/F Multicenter, Tai Po Hospital, Hong Kong SAR, China
Linda C. W. Lam*
Department of Psychiatry, The Chinese University of Hong Kong, G/F Multicenter, Tai Po Hospital, Hong Kong SAR, China
Correspondence should be addressed to: Dr Hanna Lu and Prof Linda C. W. Lam, Address: Department of Psychiatry, The Chinese University of Hong Kong, G/F Multicenter, Tai Po Hospital, Tai Po, Hong Kong, SAR China. Phone: +(852) 2831-4305; Fax: +(852) 2667-5464. Email:;
Correspondence should be addressed to: Dr Hanna Lu and Prof Linda C. W. Lam, Address: Department of Psychiatry, The Chinese University of Hong Kong, G/F Multicenter, Tai Po Hospital, Tai Po, Hong Kong, SAR China. Phone: +(852) 2831-4305; Fax: +(852) 2667-5464. Email:;



Default mode network (DMN) is vulnerable to the effects of APOE genotype. Given the reduced brain volumes and APOE ε 4-related brain changes in elderly carriers, it is less known that whether these changes would influence the functional connectivity and to what extent. This study aimed to examine the functional connectivity within DMN, and its diagnostic value with age-related morphometric alterations considered.


Whole brain and seed-based resting-state functional connectivity (RSFC) analysis were conducted in cognitively normal APOE ε 4 carriers and matched non-carriers (N=38). The absolute values of mean correlation coefficients (z-values) were used as a measure of functional connectivity strength (FCS) between DMN subregions, which were also used to estimate their diagnostic value by receiver-operating characteristic (ROC) curves.


APOE ε 4 carriers demonstrated decreased interhemispheric FCS, particularly between right hippocampal formation (R.HF) and left inferior parietal lobular (L.IPL) (t=3.487, p<0.001). ROC analysis showed that the FCS of R.HF and L.IPL could differentiate APOE ε 4 carriers from healthy counterparts (AUC value=0.734, p=0.025). Moreover, after adjusting the impact of morphometry, the differentiated value of FCS of R.HF and L.IPL was markedly improved (AUC value=0.828, p=0.002).


Our findings suggest that APOE ε 4 allele affects the functional connectivity within posterior DMN, particularly the atrophy-corrected interhemispheric FCS before the clinical expression of neurodegenerative disease.

Research Article
Copyright © International Psychogeriatric Association 2017 

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