APOE-ε4 is best known as a risk factor for Alzheimer's disease (AD). Consequently, there is considerable research interest in understanding whether APOE-ε4 influences cognition in healthy adults. Despite a substantial literature reporting effects of APOE genotype on cognition, findings are inconsistent. In particular, it is challenging to separate whether cognitive deficits in APOE-ε4 carriers reflect the influence of prodromal dementia pathology (“prodromal hypothesis”), or a direct contribution of APOE genotype to individual differences (“phenotype hypothesis”). Variable methodology across studies further complicates the issue. These challenges have limited what can be learnt about the processes underlying cognitive ageing and dementia by studying the influence of APOE genotype on cognition. In this review, we focus on the two compatible neurobiological mechanisms by which APOE genotype may influence cognition in healthy adults (prodromal and phenotype). We summarise the behavioural evidence for the influence of APOE on cognition in non-demented adults and explore key methodological challenges for disentangling the cognitive effects of different neurobiological mechanisms of APOE. Evidence suggests that at least some APOE-ε4 cognitive deficits are due to early AD pathology, whilst sensitive measures of cognition are beginning to reveal subtle cognitive differences between APOE genotypes in mid-adulthood, prior to the onset of the AD prodromal period. We conclude with recommendations for future research to investigate the cognitive consequences of neurobiological processes affected by APOE and maximise the translational potential of this research.

APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: A review / O'Donoghue, M. C.; Murphy, S. E.; Zamboni, G.; Nobre, A. C.; Mackay, C. E.. - In: CORTEX. - ISSN 0010-9452. - 104:(2018), pp. 103-123. [10.1016/j.cortex.2018.03.025]

APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: A review

Zamboni G.;
2018

Abstract

APOE-ε4 is best known as a risk factor for Alzheimer's disease (AD). Consequently, there is considerable research interest in understanding whether APOE-ε4 influences cognition in healthy adults. Despite a substantial literature reporting effects of APOE genotype on cognition, findings are inconsistent. In particular, it is challenging to separate whether cognitive deficits in APOE-ε4 carriers reflect the influence of prodromal dementia pathology (“prodromal hypothesis”), or a direct contribution of APOE genotype to individual differences (“phenotype hypothesis”). Variable methodology across studies further complicates the issue. These challenges have limited what can be learnt about the processes underlying cognitive ageing and dementia by studying the influence of APOE genotype on cognition. In this review, we focus on the two compatible neurobiological mechanisms by which APOE genotype may influence cognition in healthy adults (prodromal and phenotype). We summarise the behavioural evidence for the influence of APOE on cognition in non-demented adults and explore key methodological challenges for disentangling the cognitive effects of different neurobiological mechanisms of APOE. Evidence suggests that at least some APOE-ε4 cognitive deficits are due to early AD pathology, whilst sensitive measures of cognition are beginning to reveal subtle cognitive differences between APOE genotypes in mid-adulthood, prior to the onset of the AD prodromal period. We conclude with recommendations for future research to investigate the cognitive consequences of neurobiological processes affected by APOE and maximise the translational potential of this research.
2018
30-mar-2018
104
103
123
APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: A review / O'Donoghue, M. C.; Murphy, S. E.; Zamboni, G.; Nobre, A. C.; Mackay, C. E.. - In: CORTEX. - ISSN 0010-9452. - 104:(2018), pp. 103-123. [10.1016/j.cortex.2018.03.025]
O'Donoghue, M. C.; Murphy, S. E.; Zamboni, G.; Nobre, A. C.; Mackay, C. E.
File in questo prodotto:
File Dimensione Formato  
Odonogue2018_Cortex.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 2.65 MB
Formato Adobe PDF
2.65 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1180625
Citazioni
  • ???jsp.display-item.citation.pmc??? 74
  • Scopus 127
  • ???jsp.display-item.citation.isi??? 125
social impact