No detectable association of APOE ε4 with spatial navigation and broader cognition in healthy young adults

Abstract Alzheimer’s disease (AD) causes progressive memory loss and disorientation. It is preceded by a prolonged preclinical phase marked by pathological changes in medial temporal lobe regions involved in spatial navigation. Spatial navigation tasks have been proposed for early AD detection, and altered navigation performance was reported in older carriers of the apolipoprotein E (APOE) ε4 allele, the major genetic risk factor for sporadic AD. However, whether spatial navigation or other cognitive abilities are affected in younger ε4 carriers remains unclear. Here, we genotyped 1,000 healthy young adults (18–35 years) who completed the app-based navigation game “Sea Hero Quest” and several tasks assessing working memory, processing speed, executive functioning, and face recognition. APOE ε3ε4 carriers ( N = 88) showed no detectable differences from ε3ε3 carriers ( N = 327) on the assessed spatial navigation and cognitive measures, supported by equivalence testing and Bayesian analyses. Exploratory findings in smaller APOE ε2 subgroups (ε2ε2/ε2ε3/ε2ε4, N s = 7/51/7) suggested navigation closer to environmental borders and better memory updating, better face recognition, and faster processing speed than in ε3ε3 controls. Therefore, APOE-related behavioural differences in young adults appeared small at best, highlighting the need for paradigms sensitive to very subtle changes decades before potential dementia onset.