Table 2.

Relevant clinical studies on etiology of POCD.

Study	Study Type	Cohort	Sample size (n)	Surgical procedure(s)	Anesthetic exposure	Cognitive metrics	Key findings
Evered et al. (7)	Prospective observational	CABG, hip replacement: adults > 55 CA: adults > 50	636	Elective CABG, hip replacement, CA	CABG: general anesthesia Hip replacement: spinal anesthesia CA: sedation	Battery of seven neuropsychological tests	No difference in POCD rates between groups (CABG−16%; hip replacement−16%; CA−21%)
Geng et al. (144)	Prospective randomized	Adults > 60	150	Laparoscopic cholecystectomy	Propofol vs. sevoflurane vs. isoflurane anesthesia	Battery of eight neuropsychological tests	Lower POCD in propofol compared to sevoflurane or isoflurane on postoperative days 1 and 3
Hirsch et al. (42)	Prospective observational	Adults ≥ 55	10	Elective major knee surgery	Spinal anesthesia with propofol sedation and femoral nerve catheter	Word list test Verbal fluency test Digit symbol test	40% POCD on postoperative day 1; 20% POCD on postoperative day 2; 40% POCD on postoperative day 3
Hou et al. (147)	Prospective randomized	Adults ≥ 60; ASA 1-2	66	Elective total knee arthroplasty	Deep vs. light anesthesia† with sevoflurane and propofol, femoral and sciatic nerve blocks	MoCA Z-score < 1.96	Higher POCD in deep (20%) compared to light (3%) anesthesia
Ji et al. (41)	Prospective observational	Adults ≥ 65	83	Elective total hip replacement	Spinal anesthesia	Digit symbol substitution testConcentration endurance testNumber connection test‡	POCD rate 24.6% on postoperative day 7
Qiao et al. (145)	Prospective randomized	Adults 65–75	90	Esophageal resection	Sevoflurane vs. methylprednisone and sevoflurane vs. propofol	MoCA MMSE	Higher POCD in sevoflurane group on postoperative days 1, 3, 7
Shu et al. (146)	Prospective randomized	Females 20–60	192	Gynecologic laparoscopic surgery	Sevoflurane with remifentanil, titrated to BIS††	MMSETrail-making test	Lower POCD in 40 ≤ BIS ≤ 50 group on postoperative day 1
Silbert et al. (142)	Prospective randomized	Adults > 55 without previous neurologic deficit	100	Extracorporeal shock wave lithotripsy	General vs. spinal anesthesia	Battery of eight neuropsychological tests	No difference in POCD rates between groups
Silbert et al. (143)	Prospective randomized	Adults > 55 without previous neurologic deficit	350	Elective CABG	High-dose vs. low-dose fentanyl anesthesia	Battery of eight neuropsychological tests	Higher POCD in low-dose fentanyl group 1 week following surgery. No difference in POCD at 3 and 12 months following surgery

ASA, American Society of Anesthesiologists Classification Scale; BIS, Bispectral Index; CA, coronary angiography; CABG, coronary artery bypass graft; MMSE, Mini-mental Status Examination; MoCA, Montreal Cognitive Assessment.

^†Deep vs. light anesthesia determined by BIS values 40–50 vs. 55–65, respectively. ^††BIS values stratified to three groups: 30 ≤ BIS ≤ 40, 40 ≤ BIS ≤ 50, 50 ≤ BIS ≤ 50.

^‡Neurocognitive tests in this study amended to a Chinese protocol.