Effect of apolipoprotein E polymorphism on cognition and brain in the Cambridge Centre for Ageing and Neuroscience cohort
Rowe, James B.
Kievit, Rogier A.
Lyall, Donald M.
Fisher, Simon E.
Brain and Neuroscience Advances
MetadataShow full item record
Henson, R. N., Suri, S., Knights, E., Rowe, J. B., Kievit, R. A., Lyall, D. M., Chan, D., et al. (2020). Effect of apolipoprotein E polymorphism on cognition and brain in the Cambridge Centre for Ageing and Neuroscience cohort. Brain and Neuroscience Advances, 4 https://doi.org/10.1177/2398212820961704
Funder: Wellcome Trust; FundRef: https://doi.org/10.13039/100004440
Funder: Max-Planck-Gesellschaft; FundRef: https://doi.org/10.13039/501100004189
Funder: Alzheimer’s Research Trust; FundRef: https://doi.org/10.13039/501100000319
Polymorphisms in the apolipoprotein E (APOE) gene have been associated with individual differences in cognition, brain structure and brain function. For example, the ε4 allele has been associated with cognitive and brain impairment in old age and increased risk of dementia, while the ε2 allele has been claimed to be neuroprotective. According to the ‘antagonistic pleiotropy’ hypothesis, these polymorphisms have different effects across the lifespan, with ε4, for example, postulated to confer benefits on cognitive and brain functions earlier in life. In this stage 2 of the Registered Report – https://osf.io/bufc4, we report the results from the cognitive and brain measures in the Cambridge Centre for Ageing and Neuroscience cohort (www.cam-can.org). We investigated the antagonistic pleiotropy hypothesis by testing for allele-by-age interactions in approximately 600 people across the adult lifespan (18–88 years), on six outcome variables related to cognition, brain structure and brain function (namely, fluid intelligence, verbal memory, hippocampal grey-matter volume, mean diffusion within white matter and resting-state connectivity measured by both functional magnetic resonance imaging and magnetoencephalography). We found no evidence to support the antagonistic pleiotropy hypothesis. Indeed, Bayes factors supported the null hypothesis in all cases, except for the (linear) interaction between age and possession of the ε4 allele on fluid intelligence, for which the evidence for faster decline in older ages was ambiguous. Overall, these pre-registered analyses question the antagonistic pleiotropy of APOE polymorphisms, at least in healthy adults.
Registered Report, Cognition, apolipoprotein E, lifespan, brain, ageing
Medical Research Council (SUAG/010 RG91365)
Medical Research Council (SUAG/014 RG91365)
Medical Research Council (SUAG/051 RG91365)
Alzheimer’s Society (441)
Biotechnology and Biological Sciences Research Council (BB/H008217/1)
European Commission (732592)
External DOI: https://doi.org/10.1177/2398212820961704
This record's URL: https://www.repository.cam.ac.uk/handle/1810/311245
Embargo: ends 2020-10-07