Keenan A Walker1, Rebecca F Gottesman1,2, Aozhou Wu2, David S Knopman3, Thomas H Mosley4, Alvaro Alonso5, Anna Kucharska-Newton6, Charles H Brown7. 1. Department of Neurology, Johns Hopkins University, Baltimore, Maryland. 2. Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland. 3. Department of Neurology, Mayo Clinic, Rochester, Minnesota. 4. Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, Mississippi. 5. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia. 6. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina. 7. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.
Abstract
OBJECTIVES: To examine the association between hospitalization, critical illness, and infection occurring during middle- and late-life and structural brain abnormalities in older adults. DESIGN: Prospective cohort study. SETTING: Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS: A community sample of adults who were 44 to 66 years of age at study baseline. MEASUREMENTS: Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision, codes) on all participants over a 24-year surveillance period. Subsequently, a subset of participants underwent 3-Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)). RESULTS: Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate-adjusted regression, hospitalization was associated with 0.12-standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00-0.24) and poorer white matter microstructural integrity (0.17-SD lower FA, 95% CI=-0.27 to -0.06; 0.16-SD greater MD, 95% CI=0.07-0.25) than no hospitalization. There was a dose-dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity (p-trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (-1.64 cm3 , 95% CI=-3.16 to -0.12); major infection was associated with smaller AD signature region (-1.28 cm3 , 95% CI=-2.21 to -0.35) and larger ventricular volume (3.79 cm3 , 95% CI= 0.81-6.77). CONCLUSIONS: Whereas all-cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD.
OBJECTIVES: To examine the association between hospitalization, critical illness, and infection occurring during middle- and late-life and structural brain abnormalities in older adults. DESIGN: Prospective cohort study. SETTING:Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS: A community sample of adults who were 44 to 66 years of age at study baseline. MEASUREMENTS: Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision, codes) on all participants over a 24-year surveillance period. Subsequently, a subset of participants underwent 3-Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)). RESULTS: Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate-adjusted regression, hospitalization was associated with 0.12-standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00-0.24) and poorer white matter microstructural integrity (0.17-SD lower FA, 95% CI=-0.27 to -0.06; 0.16-SD greater MD, 95% CI=0.07-0.25) than no hospitalization. There was a dose-dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity (p-trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (-1.64 cm3 , 95% CI=-3.16 to -0.12); major infection was associated with smaller AD signature region (-1.28 cm3 , 95% CI=-2.21 to -0.35) and larger ventricular volume (3.79 cm3 , 95% CI= 0.81-6.77). CONCLUSIONS: Whereas all-cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD.
Authors: Bruce Fischl; David H Salat; Evelina Busa; Marilyn Albert; Megan Dieterich; Christian Haselgrove; Andre van der Kouwe; Ron Killiany; David Kennedy; Shuna Klaveness; Albert Montillo; Nikos Makris; Bruce Rosen; Anders M Dale Journal: Neuron Date: 2002-01-31 Impact factor: 17.173
Authors: Victor L Villemagne; Samantha Burnham; Pierrick Bourgeat; Belinda Brown; Kathryn A Ellis; Olivier Salvado; Cassandra Szoeke; S Lance Macaulay; Ralph Martins; Paul Maruff; David Ames; Christopher C Rowe; Colin L Masters Journal: Lancet Neurol Date: 2013-03-08 Impact factor: 44.182
Authors: Jin G Sheng; Susan H Bora; G Xu; David R Borchelt; Donald L Price; Vassilis E Koliatsos Journal: Neurobiol Dis Date: 2003-10 Impact factor: 5.996
Authors: Faraaz Ali Shah; Francis Pike; Karina Alvarez; Derek Angus; Anne B Newman; Oscar Lopez; Judith Tate; Vishesh Kapur; Anthony Wilsdon; Jerry A Krishnan; Nadia Hansel; David Au; Mark Avdalovic; Vincent S Fan; R Graham Barr; Sachin Yende Journal: Am J Respir Crit Care Med Date: 2013-09-01 Impact factor: 21.405
Authors: Bryan D James; Robert S Wilson; Ana W Capuano; Patricia A Boyle; Raj C Shah; Melissa Lamar; E Wesley Ely; David A Bennett; Julie A Schneider Journal: Ann Neurol Date: 2019-10-23 Impact factor: 10.422