Ce Zhang1, Yuan Han2, Xiaojun Liu3, Hong Tan4, Yuanlin Dong5, Yiying Zhang5, Feng Liang5, Hui Zheng6, Gregory Crosby7, Deborah J Culley8, Edward R Marcantonio9, Yuan Shen10, Jun-Li Cao11, Zhongcong Xie5. 1. Department of Anesthesiology, Xiang'an Hospital of Xiamen University, Xiamen, China; Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060. 2. Department of Anesthesiology, Eye & ENT Hospital of Fudan University, Shanghai, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China. 3. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China; Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060. 4. Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China; Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060. 5. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060. 6. Massachusetts General Hospital Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114. 7. Department of Anesthesia, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115. 8. Department of Anesthesia, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, Present address: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania Health System. 9. Divisions of General Medicine and Primary Care and Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. 10. Department of Psychiatry, Shanghai 10th People's Hospital, Anesthesia and Brain Research Institute, Tongji University, Shanghai, 200072, P.R. China, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060. 11. Jiangsu Province Key Laboratory of Anesthesiology; Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
Abstract
OBJECTIVE: Determine the association between olfactory function and cognition in patients and rodents. SUMMARY BACKGROUND DATA: Perioperative neurocognitive disorders include delayed neurocognitive recovery (dNCR). The contribution of olfactory function to dNCR remains undetermined. It is unknown whether odor enrichment could mitigate dNCR. METHODS: We performed a prospective observational cohort study to determine potential association between olfactory impairment and dNCR in patients. We assessed the effects of anesthesia/surgery on olfactory and cognitive function in mice using the block test and Barnes maze. We measured interleukin-6, olfactory mature protein, GAP43, mature and premature olfactory neurons, PSD-95, and synaptophysin in blood, nasal epithelium, and hippocampus of mice. Odor enrichment, interleukin-6 antibody, and knockout of interleukin-6 were used in the interaction experiments. RESULTS: Patients with dNCR had worse odor identification than the patients without dNCR [preoperative: 7 (1.25, 9) versus 10 (8, 11), median (interquartile range), P<0.001; postoperative: 8 (2.25, 10) versus 10 (8, 11), P<0.001]. Olfactory impairment associated with dNCR in patients before and after adjusting age, sex, education, preoperative mini-mental state examination score, and days of the neuropsychological tests. Anesthesia/surgery induced olfactory and cognitive impairment, increased levels of interleukin-6 in blood and nasal epithelium, decreased amounts of olfactory receptor neurons and their markers in the nasal epithelium, and reduced amounts of synapse markers in the hippocampus of mice. These changes were attenuated by odor enrichment and interleukin-6 antibody. CONCLUSION: The anesthesia/surgery-induced olfactory impairment may contribute to dNCR in patients and postoperative cognitive impairment in mice. Odor enrichment could be a potential intervention.
OBJECTIVE: Determine the association between olfactory function and cognition in patients and rodents. SUMMARY BACKGROUND DATA: Perioperative neurocognitive disorders include delayed neurocognitive recovery (dNCR). The contribution of olfactory function to dNCR remains undetermined. It is unknown whether odor enrichment could mitigate dNCR. METHODS: We performed a prospective observational cohort study to determine potential association between olfactory impairment and dNCR in patients. We assessed the effects of anesthesia/surgery on olfactory and cognitive function in mice using the block test and Barnes maze. We measured interleukin-6, olfactory mature protein, GAP43, mature and premature olfactory neurons, PSD-95, and synaptophysin in blood, nasal epithelium, and hippocampus of mice. Odor enrichment, interleukin-6 antibody, and knockout of interleukin-6 were used in the interaction experiments. RESULTS: Patients with dNCR had worse odor identification than the patients without dNCR [preoperative: 7 (1.25, 9) versus 10 (8, 11), median (interquartile range), P<0.001; postoperative: 8 (2.25, 10) versus 10 (8, 11), P<0.001]. Olfactory impairment associated with dNCR in patients before and after adjusting age, sex, education, preoperative mini-mental state examination score, and days of the neuropsychological tests. Anesthesia/surgery induced olfactory and cognitive impairment, increased levels of interleukin-6 in blood and nasal epithelium, decreased amounts of olfactory receptor neurons and their markers in the nasal epithelium, and reduced amounts of synapse markers in the hippocampus of mice. These changes were attenuated by odor enrichment and interleukin-6 antibody. CONCLUSION: The anesthesia/surgery-induced olfactory impairment may contribute to dNCR in patients and postoperative cognitive impairment in mice. Odor enrichment could be a potential intervention.