Administrative Supplement to Cognitive Resilience among Older Samoans

项目总结

PROJECT SUMMARY This proposed administrative supplement to collect new biomarkers could increase the scientific knowledge related to cognitive resilience gained from our current NIA-funded R01 entitled, “Cognitive Resilience among Older Samoans.” This supplement builds on recent developments that were unforeseen when we submitted the parent R01: (1) it was discovered that a genetic variant associated with longer telomere length (rs28372734) appears more than twice as frequently among Samoans than any other population studied; and (2) we found that our parent grant’s genetic predictor, the Pacific-Islander-specific gene variant CREBRF (rs373863828) predicts lower perceived stress in our parent R01 sample. As longer telomere length and lower stress are associated with cognitive resilience, assessing the telomere-length gene variant and stress biomarkers will allow us to determine whether these factors contribute to the mechanism by which Samoan older individuals achieve cognitive resilience. The 2 stress biomarkers that represent 2 pathways through which lower stress can benefit brain health are: (1) lower chronic inflammation, as indicated by lower CRP levels; and (2) better T-cell functioning, as indicated by lower Epstein Bar Virus (EBV) antibody levels. Thus, leveraging the strong infrastructure and enrolled sample of 600 older Samoan persons that we are following over 3 years in our parent R01, our supplement’s specific aims are to examine for the first time whether: (1) the telomere-length gene variant predicts cognitive resilience; (2) lower inflammation (as indicated by lower CRP levels) mediates the parent R01’s predictors’ (the CREBRF variant and Samoan positive age beliefs) association with cognitive resilience; and (3) adaptive T-cell function (as indicated by lower EBV antibody levels) mediates the association of the parent R01’s predictors with cognitive resilience. This proposed supplement addresses the goals of the 2022 National Plan to Address Alzheimer’s Disease3 which points out that because there are no interventions known to definitely prevent, treat or cure ADRD, there is a need to identify “the genetic underpinning of ADRD” and “the role of immunity and inflammation,” which can be impacted by stress. Further, by studying these factors in older Samoans in the US and Independent Samoa, we would contribute to NIA’s goals of increasing the study of cognitive resilience among racial and ethnic minorities in the US as well as individuals in low- and middle-income countries. By focusing on older Samoans, a group which has unique genetic and cultural qualities, this supplement could identify a new biological causal pathway to cognitive resilience that is likely to lead to future interventions for benefitting the Samoan community as well as all older persons.