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  Effect of apolipoprotein E polymorphism on cognition and brain in the Cambridge Centre for Ageing and Neuroscience cohort

Henson, R. N., Suri, S., Knights, E., Rowe, J. B., Kievit, R. A., Lyall, D. M., 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: 2398212820961704. doi:10.1177/2398212820961704.

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 Urheber:
Henson, Richard N.1, Autor
Suri, Sana2, Autor
Knights, Ethan1, Autor
Rowe, James B.1, Autor
Kievit, Rogier A.1, Autor
Lyall, Donald M.3, Autor
Chan, Dennis4, Autor
Eising, Else5, Autor           
Fisher, Simon E.5, 6, Autor           
Affiliations:
1University of Cambridge, Cambridge, UK, ou_persistent22              
2University of Oxford, Oxford, UK, ou_persistent22              
3University of Glasgow, Glasgow, UK, ou_persistent22              
4University College London, London, UK, ou_persistent22              
5Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, ou_792549              
6Donders Institute for Brain, Cognition and Behaviour, External Organizations, ou_55236              

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 Zusammenfassung: 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.

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Sprache(n): eng - English
 Datum: 20202020-10-07
 Publikationsstatus: Online veröffentlicht
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1177/2398212820961704
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Titel: Brain and Neuroscience Advances
Genre der Quelle: Zeitschrift
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Seiten: - Band / Heft: 4 Artikelnummer: 2398212820961704 Start- / Endseite: - Identifikator: -