Association of Depressive Symptoms With Postoperative Delirium and CSF Biomarkers for Alzheimer's Disease Among Hip Fracture Patients

Carol K Chan; Frederick E Sieber; Kaj Blennow; Sharon K Inouye; Geoffrey Kahn; Jeannie-Marie S Leoutsakos; Edward R Marcantonio; Karin J Neufeld; Paul B Rosenberg; Nae-Yuh Wang; Henrik Zetterberg; Constantine G Lyketsos; Esther S Oh

doi:10.1016/j.jagp.2021.02.001

Association of Depressive Symptoms With Postoperative Delirium and CSF Biomarkers for Alzheimer's Disease Among Hip Fracture Patients

Am J Geriatr Psychiatry. 2021 Dec;29(12):1212-1221. doi: 10.1016/j.jagp.2021.02.001. Epub 2021 Feb 4.

Authors

Affiliations

¹ Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.
² Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
³ Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴ Harvard Medical School, Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA; Aging Brain Center, Hebrew SeniorLife, Boston, MA.
⁵ Johns Hopkins Bloomberg School of Public Health, Baltimore MD.
⁶ Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins Bloomberg School of Public Health, Baltimore MD.
⁷ Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins University School of Nursing, Baltimore MD.
⁸ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
⁹ Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK.
¹⁰ Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
¹¹ Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins University School of Nursing, Baltimore MD. Electronic address: eoh9@jhmi.edu.

Abstract

Objectives: While there is growing evidence of an association between depressive symptoms and postoperative delirium, the underlying pathophysiological mechanisms remain unknown. The goal of this study was to explore the association between depression and postoperative delirium in hip fracture patients, and to examine Alzheimer's disease (AD) pathology as a potential underlying mechanism linking depressive symptoms and delirium.

Methods: Patients 65 years old or older (N = 199) who were undergoing hip fracture repair and enrolled in the study "A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" completed the 15-item Geriatric Depression Scale (GDS-15) preoperatively. Cerebrospinal fluid (CSF) was obtained during spinal anesthesia and assayed for amyloid-beta (Aβ) 40, 42, total tau (t-tau), and phosphorylated tau (p-tau)₁₈₁.

Results: For every one point increase in GDS-15, there was a 13% increase in odds of postoperative delirium, adjusted for baseline cognition (MMSE), age, sex, race, education and CSF AD biomarkers (OR = 1.13, 95%CI = 1.02-1.25). Both CSF Aβ42/t-tau (β = -1.52, 95%CI = -2.1 to -0.05) and Aβ42/p-tau₁₈₁ (β = -0.29, 95%CI = -0.48 to -0.09) were inversely associated with higher GDS-15 scores, where lower ratios indicate greater AD pathology. In an analysis to identify the strongest predictors of delirium out of 18 variables, GDS-15 had the highest classification accuracy for postoperative delirium and was a stronger predictor of delirium than both cognition and AD biomarkers.

Conclusions: In older adults undergoing hip fracture repair, depressive symptoms were associated with underlying AD pathology and postoperative delirium. Mild baseline depressive symptoms were the strongest predictor of postoperative delirium, and may represent a dementia prodrome.

Keywords: Alzheimer's disease; amyloid; csf; delirium; depression; hip fracture; mild behavioral impairment; tau.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease* / complications
Alzheimer Disease* / epidemiology
Amyloid beta-Peptides
Biomarkers
Delirium* / diagnosis
Delirium* / epidemiology
Delirium* / etiology
Depression / complications
Depression / epidemiology
Humans
Peptide Fragments
tau Proteins

Substances

Amyloid beta-Peptides
Biomarkers
Peptide Fragments
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding