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

Introduction By 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. Methods We 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. Results 81% 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. Discussion We 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 Context Systematic Review The 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. Interpretation Our 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 directions Validation 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. Highlights Compiled Genomic-informed dementia risk report of genetic and clinical risk factors Most memory clinic patients have at least one high-risk indicator for dementia A higher risk indicator burden is associated with a greater dementia risk