Send to

Choose Destination
Neurobiol Learn Mem. 2017 Dec;146:37-46. doi: 10.1016/j.nlm.2017.10.008. Epub 2017 Oct 12.

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

Author information

School of Social and Community Medicine, University of Bristol, Oakfield House, Bristol BS8 2BN, UK. Electronic address:
School of Experimental Psychology, University of Bristol, The Priory Road Complex, Priory Road, Bristol BS8 1TU, UK. Electronic address:
School of Social and Community Medicine, University of Bristol, Oakfield House, Bristol BS8 2BN, UK.



ε4 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.


We invited all individuals with the rarer ε22 or ε44 genotypes and equal numbers of those with ε32, ε33 or ε34 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.


114 participants were recruited to the study (39 ε33, 27 ε34, 15 ε44, 26 ε32 & 7 ε22). ε4+ participants had higher scores on the cognitive failures questionnaire (10 point increase, p = 0.006) but no deficits on objective cognitive testing. ε2 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).


It is intriguing that the ε2+ group performed better as this group have a lower risk of Alzheimer's disease. Most previous studies have analysed as ε4/non ε4 so may have missed this effect.


ALSPAC; Apolipoprotein E; Cognition; Executive functioning; Genetics; Memory episodic

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center