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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
['Lu|Hanna|H|0000-0002-9090-258X', 'Ma|Suk Ling|SL|', 'Wong|Savio Wai Ho|SW|', 'Tam|Cindy W C|CW|', 'Cheng|Sheung-Tak|ST|', 'Chan|Sandra S M|SS|', 'Lam|Linda C W|LC|']
D000368:Aged D000369:Aged, 80 and over D000375:Aging D053327:Apolipoprotein E4 D019540:Area Under Curve D001931:Brain Mapping D005260:Female D006579:Heterozygote D006624:Hippocampus D006723:Hong Kong D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D009415:Nerve Net D009434:Neural Pathways D019636:Neurodegenerative Diseases D009483:Neuropsychological Tests D009929:Organ Size D012372:ROC Curve
functional connectivity default mode network Alzheimer's disease apolipoprotein E neurocognitive disorder