Association of mid-age Life’s Essential 8 score with digital cognitive performance and incident Alzheimer’s disease: the Framingham Heart Study

Background Emerging studies indicate that cardiovascular health (CVH) is a modifiable risk factor for AD. However, studies on how mid-life Life’s Essential 8 (LE8) scores affect the AD risk and digital cognitive performance are limited. Objective To examine the associations between CVH in middle age, as defined by LE8 scores, and subsequent digital cognitive performance and incident AD. Methods Linear regression and Cox proportional-hazard models were used to examine the associations of mid-age CVH with dCDT performance and incident AD, respectively. Prediction performance of mid-age LE8 scores for incident AD were assessed using ROC curve analysis. Results Every one-SD increase in mid-age LE8 total score was associated with a 0.16-SD increase in dCDT total score (p < 0.001). Ideal CVH in middle age was associated with higher dCDT scores compared to intermediate CVH. Furthermore, higher mid-age LE8 scores were associated to a decreased risk of AD, with ideal CVH significantly lowering AD risk compared to intermediate CVH. The combination of dCDT performance, mid-age LE8 scores, APOE ε4 status, and other covariates provided the best prediction performance for incident AD, with an AUC of 0.84. Notably, mid-life LE8 scores improved its predictive accuracy by 5.7%. Conclusion Our findings emphasize the critical role of CVH in middle age as a predictor of both digital cognitive performance and the risk of developing AD, highlighting the importance of early intervention on CVH to delay the progression of cognitive decline. ### Competing Interest Statement Dr. Au is a scientific advisor to Signant Health and NovoNordisk, and a consultant to the Davos Alzheimer’s Collaborative. The other authors state that this study was carried out without any commercial or financial affiliations that might be seen as a possible conflict of interest. ### Funding Statement This work was supported by National Heart, Lung, and Blood Institute contract (N01-HC-25195; HHSN268201500001I), and NIH grants from the National Institute on Aging (AG008122, AG062109, AG068753) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The institutional review board at Boston University gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data used in this study could be requested through an application to the Framingham Heart Study.