Genome-wide Association Study of Postoperative Cognitive Dysfunction in Older Surgical Patients

Abstract

Background: Postoperative cognitive dysfunction (POCD) is a common neurocognitive complication after surgery and anesthesia, particularly in elderly patients. Various studies have suggested genetic risk factors for POCD. The study aimed to detect genome-wide associations of POCD in older patients. Methods: In this prospective observational cohort study, participants aged ≥65 years completed a set of neuropsychological tests before, at 1 week, and 3 months after major noncardiac surgery. Test variables were converted into standard scores (z-scores) based on demographic characteristics. POCD was diagnosed if the decline was >1 standard deviation in ≥2 of the 15 variables in the assessment battery. A genome-wide association study (GWAS) was performed to determine potential alleles that are linked to the POCD phenotype. In addition, candidate genes for POCD were identi ed in a literature search for further analysis.Results: Sixty-three patients with blood samples were included in the study. POCD was diagnosed in 47.6% of patients at 1 week and in 34.2% of patients at 3 months after surgery. Insu cient sample quality led to exclusion of 26 patients. In the remaining 37 patients, a GWAS was performed, but no association (P < 5*10 -8 ) with POCD was found. The subsequent gene set enrichment analysis of 34 candidate genes did not reveal any signi cant associations. Conclusion:In this patient cohort, a GWAS did not reveal an association between speci c genetic alleles and POCD at 1 week and 3 months after surgery. Future genetic analysis should focus on speci c candidate genes for POCD.

Risk assessment of perioperative neurocognitive disorders, where are we now?

“…In genome-wide association studies of POCD, neither Rickenbacher et al [18] nor Heinrich et al [19 ▪▪ ] could find any significant association. However, three genetic variants of the cholinergic receptor muscarinic 2 and 4 (CHRM2 and CHRM4) were associated with the development of POD [19 ▪▪ ].…”

Caloric Restriction Can Ameliorate Postoperative Cognitive Dysfunction by Upregulating the Expression of Sirt1, MeCP2 and BDNF in the Hippocampal CA1 Region of Aged C57BL/6 Mice

“…Postoperative cognitive dysfunction (POCD) is a common neurocognitive complication after surgery in the elderly, and is characterized by functional impairments, such as memory, executive function, direction, emotion, and visual–spatial structural ability [ 1 , 2 ]. According to recent research, elderly people over 65 years were highly likely to have POCD; moreover, the incidence can reach up to 47.6% of patients at one week and 34.2% of patients at three months after surgery [ 3 ]. There are numerous risk factors for POCD, including aging, educational level, inappropriate diet, obesity, anesthesia, surgery, etc.…”

Relationships of serum VILIP-1, NSE, and ADP levels with postoperative cognitive dysfunction in elderly patients undergoing general anesthesia: a retrospective, observational study

“…Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients after anesthesia that manifests as memory impairment occurring a few days to weeks after surgery, decreased ability to learn and recall information, reduced concentration, disordered comprehension of language, and diminished decision-making and social adaptation. 1 Some studies suggested that age, hypoxia, hypotension, anesthesia, and surgical trauma can induce POCD. 2 , 3 Some studies also indicated that the inflammatory reaction induced by surgery might influence the occurrence of POCD and that suppressing the inflammatory reaction could reduce the incidence and severity of POCD.…”