Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls

• Published in: Anesthesiology (Philadelphia) Vol. 140; no. 5; pp. 963 - 978
• Main Authors: Reese, Melody, Wong, Megan K, Cheong, Vanessa, Ha, Christine I, Cooter Wright, Mary, Browndyke, Jeffrey, Moretti, Eugene, Devinney, Michael J, Habib, Ashraf S, Moul, Judd W, Shaw, Leslie M, Waligorska, Teresa, Whitson, Heather E, Cohen, Harvey J, Welsh-Bohmer, Kathleen A, Plassman, Brenda L, Mathew, Joseph P, Berger, Miles
• Format: Journal Article
• Language: English
• Published: United States 01-05-2024
• Subjects: Aged; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognition; Cognitive Dysfunction - diagnosis; Humans; Peptide Fragments; tau Proteins
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0000000000004924

Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults.
The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid β (Aβ) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls.
The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aβ, tau, or p-tau levels, or tau/Aβ or p-tau/Aβ ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (β, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up.
During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aβ) changes or greater cognitive decline.