Perioperative polygenic and APOE-based genetic risk assessment for neurocognitive disorders: a biobank study.
Level 3 - non-randomized controlled study
Non-randomized retrospective cohort study using biobank data
PubMed 40562635 · doi:10.1016/j.bja.2025.05.014
What was done
Data from 33,526 surgical patients aged 40-89 years without a previous diagnosis of Alzheimer's disease were analyzed from the Mass General Brigham Biobank. Investigators calculated polygenic risk scores for Alzheimer's disease and inferred APOE genotypes, then used logistic regression to examine associations with postoperative neurocognitive disorders.
What was found
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 was associated with higher risk of Alzheimer's disease (odds ratio 2.25, 95% confidence interval 1.64-3.09, false discovery rate < 0.001). APOE-ε4 carriers had increased risks for delirium (odds ratio 1.32, 95% confidence interval 1.19-1.47, false discovery rate < 0.001), mild cognitive impairment (odds ratio 1.70, 95% confidence interval 1.49-1.94, false discovery rate < 0.001), and Alzheimer's disease (odds ratio 3.42, 95% confidence interval 2.72-4.29, false discovery rate < 0.001).
Why it matters
This study shows that established genetic markers for dementia are associated with both acute and long-term postoperative neurocognitive outcomes. It suggests that genetic profiling could help stratify perioperative risk.
Limits
The polygenic risk score analysis was limited to patients of European ancestry (86% of the cohort). The abstract does not report specific surgical types, anesthesia details, baseline cognitive assessments, or timing of postoperative outcome ascertainment. Biobank observational designs carry risks of residual confounding and outcome misclassification.
Cited by
- supports Between 20% and 25% of Americans carry the APOE4 allele.