Abstract
Background
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.
Methods
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 hour 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 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).
Conclusions
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.
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.
Methods
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 hour 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 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).
Conclusions
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.
| Original language | English |
|---|---|
| Pages (from-to) | 37-46 |
| Number of pages | 10 |
| Journal | Neurobiology of Learning and Memory |
| Volume | 146 |
| Early online date | 12 Oct 2017 |
| DOIs | |
| Publication status | Published - 1 Dec 2017 |
Research Groups and Themes
- Brain and Behaviour
- Cerebrovascular and Dementia Research Group
Keywords
- ALSPAC
- Apolipoprotein E
- Cognition
- Executive functioning
- Genetics
- Memory episodic