Carol K Chan1, Frederick E Sieber2, Kaj Blennow3, Sharon K Inouye4, Geoffrey Kahn5, Jeannie-Marie S Leoutsakos6, Edward R Marcantonio4, Karin J Neufeld7, Paul B Rosenberg1, Nae-Yuh Wang8, Henrik Zetterberg9, Constantine G Lyketsos10, Esther S Oh11. 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.
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.
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