Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Targeting modifiable risk factors may help to prevent Alzheimer's disease (AD), but the pathways by which these risk factors influence AD risk remain incompletely understood. We identified genome-wide association studies for AD and its major modifiable risk factors. We calculated the genetic correlation among these traits and modelled this using genomic structural equation modelling. We identified complex networks of genetic overlap among AD risk factors, but AD itself was largely genetically distinct. The data were best explained by a bi-factor model, incorporating a Common Factor for AD risk, and 3 orthogonal sub-clusters of risk factors. Taken together, our findings suggest that there is extensive shared genetic architecture between AD modifiable risk factors, but this is largely independent of AD genetic pathways. Extensive genetic pleiotropy between risk factors may influence AD indirectly by decreasing cognitive reserve or increasing risk of multimorbidity, leading to poorer brain health. Further work to understand the biology reflected by this communality may provide novel mechanistic insights that could help to prioritise targets for dementia prevention.

Original publication




Journal article


Neurobiol Aging

Publication Date





222 - 235


Alzheimer's disease, Dementia, Dementia prevention, Risk factors, Shared genetics, genomic SEM