Possible positive effect of the APOE ε2 allele on cognition in early to mid-adult life.

Abstract Background e4 allele possession is associated with an increased risk of Alzheimer’s disease. Its effects earlier in life are less well understood. Previous studies have reported both detrimental effects and a lack of effect on cognition outside dementia. We used genotype based recall from the ALSPAC study to investigate whether APOE genotype influences cognition in earlier adult life. Methods We invited all individuals with the rarer e22 or e44 genotypes and equal numbers of those with e32, e33 or e34 APOE genotypes (total n invited = 1936, ages 23–67). Participants were screened for dementia using the Addenbrooke’s Cognitive Examination Revised (ACE-R). Participants were asked to complete a 3 h battery of neuropsychological tests covering a range of cognitive domains. The primary outcome was performance on the Rey Auditory Verbal Learning Test (RAVLT). Transformation of variables was used where required to permit parametric testing. As genotypes are unlikely to be confounded unadjusted analyses were performed. Results 114 participants were recruited to the study (39 e33, 27 e34, 15 e44, 26 e32 & 7 e22). e4+ participants had higher scores on the cognitive failures questionnaire (10 point increase, p = 0.006) but no deficits on objective cognitive testing. e2 carriers had slightly better episodic memory performance (p = 0.016), slightly improved n-back accuracy and better executive functioning (trails A&B, p = 0.005). Conclusions It is intriguing that the e2+ group performed better as this group have a lower risk of Alzheimer’s disease. Most previous studies have analysed as e4/non e4 so may have missed this effect.