title: Aberrant interhemispheric functional connectivity within default mode network and its relationships with neurocognitive features in cognitively normal APOE ε 4 elderly carriers.
abstract: 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.
authors.affiliation: Department of Psychiatry,The Chinese University of Hong Kong,G/F Multicenter,Tai Po Hospital,Hong Kong SAR,China.
authors.forename: Hanna
authors.identifier: 0000-0002-9090-258X
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Psychiatry,The Chinese University of Hong Kong,G/F Multicenter,Tai Po Hospital,Hong Kong SAR,China.
authors.forename: Suk Ling
authors.initials: SL
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Savio Wai Ho
authors.initials: SW
authors.lastname: Wong
authors.affiliation: Department of Psychiatry,The Chinese University of Hong Kong,G/F Multicenter,Tai Po Hospital,Hong Kong SAR,China.
authors.forename: Cindy W C
authors.initials: CW
authors.lastname: Tam
authors.affiliation: Department of Health and Physical Education,The Education University of Hong Kong,Hong Kong SAR,China.
authors.forename: Sheung-Tak
authors.initials: ST
authors.lastname: Cheng
authors.affiliation: Department of Psychiatry,The Chinese University of Hong Kong,G/F Multicenter,Tai Po Hospital,Hong Kong SAR,China.
authors.forename: Sandra S M
authors.initials: SS
authors.lastname: Chan
authors.affiliation: Department of Psychiatry,The Chinese University of Hong Kong,G/F Multicenter,Tai Po Hospital,Hong Kong SAR,China.
authors.forename: Linda C W
authors.initials: LC
authors.lastname: Lam
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000523:psychology; D053327:Apolipoprotein E4 / Q000235:genetics*; D019540:Area Under Curve; D001931:Brain Mapping; D005260:Female; D006579:Heterozygote; D006624:Hippocampus / Q000502:physiology*; D006723:Hong Kong; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging*; D009434:Neural Pathways / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D009483:Neuropsychological Tests; D009929:Organ Size; D012372:ROC Curve
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer's disease; apolipoprotein E; default mode network; functional connectivity; neurocognitive disorder