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

Author:

Reese Melody1ORCID,Wong Megan K.2,Cheong Vanessa3,Ha Christine I.4,Cooter Wright Mary5,Browndyke Jeffrey6,Moretti Eugene7,Devinney Michael J.8,Habib Ashraf S.9,Moul Judd W.10,Shaw Leslie M.11,Waligorska Teresa12,Whitson Heather E.13,Cohen Harvey J.14,Welsh-Bohmer Kathleen A.15,Plassman Brenda L.16,Mathew Joseph P.17,Berger Miles18, ,Amundsen C. L.,Bengali S.,Bennett E.,Berry M. F.,Blazer D. G.,Bolognesi M. P.,Brassard R.,Brigman B. E.,Bullock M.,Carter J.,Chapman J.,Colin B.,D’Amico T. A.,DeOrio J. K.,Erdmann D.,Esclamado R. M.,Ferrandino M.,Funk B.,Gadsden J.,Gardner J.,Garrigues G.,Giattino C.,Gold D. T.,Grant S.,Guercio J.,Gupta D. K.,Habib A.,Harpole D. H.,Harris S. M.,Hartwig M. G.,Hollenbeck S. T.,Hu J.,Iboaya E.,Inman B. A.,Jang D. W.,Kaisen J.,Khan A.,Lagoo-Deenadayalan S.,Laskowitz D. T.,Lee P. S.,Lee W. T.,Lemm J.,Levinson H.,Lipkin M. E.,Mantyh C. R.,McDonagh D. L.,Migaly J.,Mithani S. K.,Mosca P.,Moul J.,Newman M. F.,Ni K.,Ohlendorf B.,Onaitis M. W.,Pappas T. N.,Perez A. N.,Peterson A. C.,Polascik T. J.,Podgoreanu A.,Preminger G. M.,Quinones Q.,Rampersaud E. N.,Ray A.,Roberts K.,Robertson C. N.,Roman S. A.,Runyon S.,Sandler A.,Sbahi F.,Scales C. D.,Scheri R. P.,Smith S. K.,Talbot L.,Thacker J. K. M.,Thomas J.,Tong B. C.,Toulgoat-Dubois Y.,Tu A.,Vaslef S. N.,Whittle J.,Woldorff M.,Waldron N.,Warner D. S.,Wang X.,Wellman S. S.,Wickenheisser T.,Young C.,Zani S.

Affiliation:

1. 1Department of Anesthesiology, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina.

2. 2Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.

3. 3Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; Duke University–National University of Singapore Medical School, Singapore.

4. 4Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.

5. 5Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.

6. 6Department of Psychiatry and Behavioral Medicine, Duke University Medical Center, Durham, North Carolina.

7. 7Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.

8. 8Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.

9. 9Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.

10. 10Department of Anesthesiology, and Department of Surgery, Duke University Medical Center, Durham, North Carolina.

11. 11Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

12. 12Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

13. 13Center for the Study of Aging and Human Development, Department of Medicine, and Duke/University of North Carolina Alzheimer’s Disease Research Center, Duke University Medical Center, Durham, North Carolina.

14. 14Center for the Study of Aging and Human Development, Department of Medicine, and Duke/University of North Carolina Alzheimer’s Disease Research Center, Duke University Medical Center, Durham, North Carolina.

15. 15Department of Psychiatry and Behavioral Medicine, and Duke/University of North Carolina Alzheimer’s Disease Research Center, Duke University Medical Center, Durham, North Carolina.

16. 16Department of Psychiatry and Behavioral Medicine, and Duke/University of North Carolina Alzheimer’s Disease Research Center, Duke University Medical Center, Durham, North Carolina.

17. 17Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.

18. 18Department of Anesthesiology, Center for the Study of Aging and Human Development, and Duke/University of North Carolina Alzheimer’s Disease Research Center, Duke University Medical Center, Durham, North Carolina.

Abstract

Background 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. Methods 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. Results 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. Conclusions 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. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Publisher

Ovid Technologies (Wolters Kluwer Health)

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