Possible Positive Effect Of The Apoe Epsilon 2 Allele On Cognition In Early To Mid Adult Life

Background epsilon 4 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 epsilon 22 or epsilon 44 genotypes and equal numbers of those with epsilon 32, epsilon 33 or epsilon 34 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 epsilon 33, 27 epsilon 34, 15 epsilon 44, 26 epsilon 32 & 7 epsilon 22). epsilon 4 + participants had higher scores on the cognitive failures questionnaire (10 point increase, p = 0.006) but no deficits on objective cognitive testing. epsilon 2 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 epsilon 2+ group performed better as this group have a lower risk of Alzheimer's disease. Most previous studies have analysed as epsilon 4/non epsilon 4 so may have missed this effect.