Hereditary vulnerabilities to post-operative cognitive dysfunction and dementia

• Patients differ in vulnerability to persistent cognitive changes after surgery.
• No DNA predictors of persistent post-operative cognitive changes are known.
• Consensual post-operative cognitive phenotypes are essential before genotyping.
• Surgical and anesthetic descriptors should be added to ongoing dementia protocols.
• Genotypes of patients with severe cognitive phenotypes after surgery are a priority.

In view of multiple prospective investigations reporting an incidence of 10% or greater in elderly patients after cardiac and non-cardiac procedures, it is surprising that no families, twins or even individual cases have been reported with persistent post-operative cognitive dysfunction (POCD) or post-operative dementia (POD) that is otherwise unexplained. As POCD and POD research has shifted in recent years from surgical and anesthetic variables to predictors of intrinsic, patient-specific susceptibility, a number of markers based on DNA sequence variation have been investigated. Nevertheless, no heritable, genomic indices of persistent POCD or post-operative dementia lasting 3 months or longer after surgery have been identified to date. The present manuscript surveys challenges confronting the search for markers of heritable vulnerability to POCD and POD, and proposes steps forward to be taken now, including the addition of surgical and anesthetic descriptors to ongoing longitudinal dementia protocols and randomized clinical trials (RCTs) comprising serial psychometric testing, and a fresh focus on phenotypes and genotypes shared between outliers with “extreme” POCD and POD traits.