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BACKGROUND: Preoperative risk assessment is a critical step in developing targeted preventive and therapeutic strategies. Although genetic biomarkers have shown considerable promise in assessing and stratifying dementia risk, their application in the perioperative period remains unexplored. Given the recognised effects of surgery and anaesthesia on perioperative cognitive trajectories, this study aimed to evaluate the preoperative neurocognitive genetic risk profiles of a surgical population and their influence on postoperative outcomes.METHODS: Data from the Mass General Brigham Biobank were analysed for male and female surgical patients aged 40-89 yr without a previous diagnosis of Alzheimer's disease. The polygenic risk score for Alzheimer's disease was calculated, and apolipoprotein E (APOE) genotypes were inferred from the study participants. Logistic regression was used to examine the associations between APOE genotype and the polygenic risk score for Alzheimer's disease with neurocognitive disorders.RESULTS: The surgical population comprised 33 526 patients, of whom 86% had European ancestry and 25% carried at least one APOE-ε4 allele. Among patients of European ancestry, the polygenic risk score for Alzheimer's disease was associated with higher risk of Alzheimer's disease (odds ratio [OR], 2.25 [95% confidence interval, 1.64-3.09]; false discovery rate [FDR] <0.001). Patients carrying APOE-ε4 alleles had an increased risk of neurocognitive disorders (e.g. delirium: OR, 1.32 [1.19-1.47], FDR <0.001; mild cognitive impairment: OR, 1.70 [1.49-1.94], FDR <0.001; and Alzheimer's disease: OR, 3.42 [2.72-4.29], FDR <0.001).CONCLUSIONS: APOE genotypes and polygenic risk scores are valuable for exploring neurocognitive genetic risk profiles in surgical populations and have the potential to enhance preoperative risk assessment strategies.