title: Neural substrates of vulnerability to postsurgical delirium as revealed by presurgical diffusion MRI.
abstract: Despite the significant impact of postoperative delirium on surgical outcomes and the long-term prognosis of older patients, its neural basis has not yet been clarified. In this study we investigated the impact of premorbid brain microstructural integrity, as measured by diffusion tensor imaging before surgery, on postoperative delirium incidence and severity, as well as the relationship among presurgical cognitive performance, diffusion tensor imaging abnormalities and postoperative delirium. Presurgical diffusion tensor imaging scans of 136 older (≥70 years), dementia-free subjects from the prospective Successful Aging after Elective Surgery study were analysed blind to the clinical data and delirium status. Primary outcomes were postoperative delirium incidence and severity during the hospital stay, as assessed by the Confusion Assessment Method. We measured cognition before surgery using general cognitive performance, a composite score based on a battery of neuropsychological tests. We investigated the association between presurgical diffusion tensor imaging parameters of brain microstructural integrity (i.e. fractional anisotropy, axial, mean and radial diffusivity) with postoperative delirium incidence and severity. Analyses were adjusted for the following potential confounders: age, gender, vascular comorbidity status, and general cognitive performance. Postoperative delirium occurred in 29 of 136 subjects (21%) during hospitalization. Presurgical diffusion tensor imaging abnormalities of the cerebellum, cingulum, corpus callosum, internal capsule, thalamus, basal forebrain, occipital, parietal and temporal lobes, including the hippocampus, were associated with delirium incidence and severity, after controlling for age, gender and vascular comorbidities. After further controlling for general cognitive performance, diffusion tensor imaging abnormalities of the cerebellum, hippocampus, thalamus and basal forebrain still remained associated with delirium incidence and severity. This study raises the intriguing possibility that structural dysconnectivity involving interhemispheric and fronto-thalamo-cerebellar networks, as well as microstructural changes of structures involved in limbic and memory functions predispose to delirium under the stress of surgery. While the diffusion tensor imaging abnormalities observed in the corpus callosum, cingulum, and temporal lobe likely constitute the neural substrate for the association between premorbid cognition, as measured by general cognitive performance, and postoperative delirium, the microstructural changes observed in the cerebellum, hippocampus, thalamus and basal forebrain seem to constitute a separate phenomenon that predisposes to postsurgical delirium independent of presurgical cognitive status.
authors.affiliation: Center for Neurological Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavallari
authors.affiliation: Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Computer Science, State University of New York at Binghamton, Binghamton, NY, USA.
authors.forename: Weiying
authors.initials: W
authors.lastname: Dai
authors.affiliation: Center for Neurological Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Charles R G
authors.initials: CR
authors.lastname: Guttmann
authors.affiliation: Center for Neurological Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Dominik S
authors.initials: DS
authors.lastname: Meier
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School.
authors.forename: Long H
authors.initials: LH
authors.lastname: Ngo
authors.affiliation: Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
authors.forename: Tammy T
authors.initials: TT
authors.lastname: Hshieh
authors.affiliation: Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Callahan
authors.affiliation: Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Tamara G
authors.initials: TG
authors.lastname: Fong
authors.affiliation: Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Schmitt
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Charlestown, MA, USA Psychiatric Neuroimaging Division, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Charlestown, MA, USA Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Charlestown, MA, USA.
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Dickerson
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel Z
authors.initials: DZ
authors.lastname: Press
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Marcantonio
authors.affiliation: Departments of Psychiatry and Human Behavior and Neurology, Brown University Warren Alpert Medical School, Providence, RI, USA.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Jones
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Inouye
authors.affiliation: Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA dalsop@bidmc.harvard.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Alsop
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology / Q000523:psychology; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003693:Delirium / Q000175:diagnosis* / Q000209:etiology / Q000523:psychology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D017558:Elective Surgical Procedures / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D011183:Postoperative Complications / Q000175:diagnosis* / Q000209:etiology / Q000523:psychology; D011300:Preoperative Care / Q000379:methods*; D011446:Prospective Studies
keywords: cognitive ageing; delirium; neuropsychiatry; structural MRI; temporal lobe