The Role of Genomic-Informed Risk Assessments in Predicting Dementia Outcomes

Abstract

IntroductionBy integrating genetic and clinical risk factors into genomic-informed dementia risk reports, healthcare providers can offer patients detailed risk profiles to facilitate understanding of individual risk and support the implementation of personalized strategies for promoting brain health. MethodsWe constructed an additive score comprising the modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score (mCAIDE), family history of dementia, APOE genotype, and an AD polygenic risk score in NACC and ADNI, and assessed its association with progression to all-cause dementia. Results81% of participants had at least one high-risk indicator for dementia, with each additional risk indicator linked to a 34% increase in the hazard of dementia onset. DiscussionWe found that most participants in memory and aging clinics had at least one high-risk indicator for dementia. Furthermore, we observed a dose-response relationship where a greater number of risk indicators was associated with an increased risk of incident dementia. Research in ContextO_ST_ABSSystematic ReviewC_ST_ABSThe authors reviewed the literature using traditional sources (e.g. PubMed), focusing on integrating genetic and non-genetic risk factors for dementia prediction. We identified a knowledge gap regarding what proportion of patients evaluated at memory and aging clinics have high-risk indicators for dementia based on their family history, monogenic mutations, APOE genotype, polygenic risk scores, and clinical risk factors; and what is the association of risk-indicator burden with incident dementia. InterpretationOur findings highlight that most patients possess at least one high-risk indicator for dementia, with a higher burden associated with a greater dementia risk. Compiling high-risk dementia indicators into a genomic-informed risk assessment could facilitate a better understanding of individual risk and support the implementation of personalized strategies for promoting brain health. Future directionsValidation of genomic-informed risk reports is needed in longitudinal population-based studies and assessing the clinical utility of genomic risk reports to promote brain health for dementia prevention. HighlightsO_LICompiled Genomic-informed dementia risk report of genetic and clinical risk factors C_LIO_LIMost memory clinic patients have at least one high-risk indicator for dementia C_LIO_LIA higher risk indicator burden is associated with a greater dementia risk C_LI