Public Health.

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• Postoperative delirium (POD) affects up to one-third of surgical patients, increasing morbidity and mortality.
• The genetic risk factor APOE-ε4 for Alzheimer's disease (AD) has an inconsistent association with POD.
• Investigating polygenic risk scores for AD (AD-PRS) may clarify POD susceptibility.

Purpose of the Study:

• To determine if a higher AD-PRS predicts an increased risk of POD in patients without pre-existing dementia.
• To examine how sleep burden modifies the relationship between AD-PRS and POD risk.

Main Methods:

• Prospective cohort study of 500,000 UK Biobank participants over a 12-year median follow-up.
• POD cases identified via ICD-10 coding within three days of surgery; participants with pre-existing dementia excluded.
• Cox proportional hazard models used to assess AD-PRS association with POD risk, adjusting for covariates and sleep burden.

Main Results:

• Higher AD-PRS quartiles showed a stepwise increase in POD risk compared to the lowest quartile.
• Individuals in the highest AD-PRS quartiles (Q3 and Q4) had significantly higher POD risk (HR 1.23-1.35).
• AD-PRS remained a consistent predictor of POD risk across different sleep burden levels, sexes, and age groups.

Conclusions:

• Elevated AD-PRS is independently associated with increased POD risk in adults without dementia.
• The predictive power of AD-PRS for POD is consistent across sleep burden, sex, and age.
• Findings suggest polygenic Alzheimer's risk contributes to surgical delirium susceptibility beyond APOE-ε4.