Impact of <i>APOE</i> ε4 allele on associations between sub‐threshold, positive Amyloid‐β retention, brain function, and cognitive performances in cognitively normal older adults

Background A growing body of evidence suggests a deteriorating effect sub-threshold amyloid-beta (Aβ) accumulation on cognition before the onset clinical symptoms Alzheimer’s disease. Despite association between Aβ-dependent pathway and APOE ε4 allele, impact this allele progression from Aβ deposits to cognitive function impairment is unclear. Furthermore, comparative analysis positive in preclinical phase lacking. This study aimed explore differential retention, brain function, performance cognitively healthy older adults, depending burden status. Method One hundred eighty-two adults with normal who underwent resting-state functional magnetic resonance imaging were enrolled. They dichotomized using [18F]-labeled flutemetamol positron emission tomography into subjects (cognitively [CN] sub-Aβ, n = 110; [APOE carrier, 30; non-carrier, 80] [CN Aβ+ group, 72; 34; 38]). Result We found (i) distinct effects relationships phase; (ii) differences local connectivity (FC) regions networks vulnerable disease according which was associated higher executive memory function; (iii) regional retention FC allele; (iv) significant interaction for remote inter-network default-mode central-executive network CN sub-Aβ contributing compensatory role performance. Finally, these results modulated positivity. Conclusion first attempt thoroughly examine mechanism at play earliest disease, focusing influence during phase.