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Abstract

Objective:

To determine whether hospitalization is associated with subsequent cognitive decline or changes on brain MRI in a community-based cohort.

Methods:

Baseline and follow-up cognitive testing (n = 2,386) and MRI scans with standardized assessments (n = 885) were available from a subset of white and black participants in the Atherosclerosis Risk in Communities study. Cognitive tests included the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). Hospitalization characteristics were determined using ICD-9 codes. Regression models adjusted for demographics, education, comorbidities, and APOE ε4 were used to estimate the independent association of hospitalization with changes in cognition or neuroimaging.

Results:

Over a mean 14.1 years between visits, 1,266 participants (53.1%) were hospitalized. Hospitalization compared with no hospitalization was associated with greater decline in DSST scores (1.25 points greater decline, p < 0.001) but no difference in DWRT or WFT score change. Each additional hospitalization, as well as a critical illness vs noncritical illness hospitalization, was associated with greater decline in DSST scores. A subset of participants (n = 885) underwent MRI scans separated by 10.5 years. Hospitalization (n = 392) compared with no hospitalization was associated with a 57% higher odds of increasing ventricular size at follow-up. Each additional hospitalization, as well as having a critical illness vs noncritical illness hospitalization, and having a hospitalization with major surgery vs no surgery was associated with greater odds of increased ventricular size.

Conclusions:

Cognitive decline and neuroimaging changes may occur after hospitalization, independent of baseline demographics and comorbidities.

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Information & Authors

Information

Published In

Neurology®
Volume 84Number 14April 7, 2015
Pages: 1443-1453
PubMed: 25762715

Publication History

Received: April 30, 2014
Accepted: December 22, 2014
Published online: March 11, 2015
Published in print: April 7, 2015

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Disclosure

C. Brown, A. Sharrett, J. Coresh, A. Schneider, and A. Alonso report no disclosures relevant to the manuscript. D. Knopman serves as Deputy Editor for Neurology® and serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the Dominantly Inherited Alzheimer's Disease Treatment Unit; served on a Data Safety Monitoring Board for Lilly Pharmaceuticals; served as a consultant to Tau RX; was an investigator in clinical trials sponsored by Baxter and Elan Pharmaceuticals in the past 2 years; and receives research support from the NIH. T. Mosley and R. Gottesman report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Study Funding

Andrea Schneider was supported by NHLBI grant 5T32HL007024. Charles Brown was supported by R01 AG033615-01A1 NIH KL-2 Clinical Research Scholars Program, RO3 AG042331, and Jahnigen Career Development Award. ARIC is conducted as a collaborative study supported by National Heart, Lung, and Blood Institute Contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. ARIC carotid MRI examination is funded by U01HL075572-01 and the ARIC brain MRI examination is funded by grant R01-HL70825. Neurocognitive data are collected by U01 HL096812, HL096814, HL096899, HL096902, and HL096917. Infrastructure is partly supported by grant UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This study was not industry-sponsored.

Authors

Affiliations & Disclosures

Charles H. Brown, IV, MD, MHS
From Johns Hopkins School of Medicine (C.H.B., A.L.C.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health (A.R.S., J.C., A.L.C.S.), Baltimore, MD; University of Minnesota (A.A.), Minneapolis; Mayo Clinic (D.S.K.), Rochester, MN; and University of Mississippi Medical Center (T.H.M.), Jackson.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
R01 AG033615-01A1 NIH KL-2 Clinical Research Scholars Program, 2011-2013 RO3 AG042331, 2012-2014 Research Career Development Core of the Johns Hopkins University Claude D. Pepper Older Americans Independence Center, National Institute on Aging (NIA), P30AG021334 ; 2014-present
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Jahnigen Career Development Award, 2012-2014
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
A. Richey Sharrett, MD, PhD
From Johns Hopkins School of Medicine (C.H.B., A.L.C.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health (A.R.S., J.C., A.L.C.S.), Baltimore, MD; University of Minnesota (A.A.), Minneapolis; Mayo Clinic (D.S.K.), Rochester, MN; and University of Mississippi Medical Center (T.H.M.), Jackson.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Josef Coresh, MD, PhD, MHS
From Johns Hopkins School of Medicine (C.H.B., A.L.C.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health (A.R.S., J.C., A.L.C.S.), Baltimore, MD; University of Minnesota (A.A.), Minneapolis; Mayo Clinic (D.S.K.), Rochester, MN; and University of Mississippi Medical Center (T.H.M.), Jackson.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Amgen, for-profit, $4000 for preparation & giving a plenary talk at a workshop
Editorial Boards:
1.
Associate Editor, American Journal of Epidemiology
Patents:
1.
ABCG2 as a mechanism for gout treatment (irrelevant for this & not lisenced).
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Professor, Johns Hopkins University
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH & NKF -- non-profit grants: ACTIVE (costs are direct costs for all and current year of each grant) N01-HC-55020 Coresh (PI) 2/01/06 ? 01/31/12 3.18 calendar NIH/NHLBI Total Direct Cost: $6,613,808 ; 2008: $826,629 Atherosclerosis Risk in Communities (ARIC) Study Field Center Examines the etiology and natural history of atherosclerosis, coronary heart disease, and measures variation in cardiovascular risk factors, medical care and disease by race, sex, place, and time including both a cohort and a surveillance component. R01DK076770-01 Brad Astor (PI) 2/1/07-11/30/12 1.80 calendar NIH/NIDDK Total Direct Costs: $1,048,666; 2008: $519,186 Longitudinal study of predictors and consequences of chronic kidney disease Study consequences of CKD prospectively from ARIC visit 4, conduct a case-cohort study of predictors of CKD, conduct a genetic investigation of CKD in ARIC with replication in other cohorts. UL1-RR025005-01 Ford (PI) 9/17/2007-5/31/2012 2.10 calendar NIH/NCRR Total Direct Cost: $73,406,888; 2008: $10,707,230 ICTR Multidisciplinary Clinical Research Career Development Program This project seeks to establish a Multidisciplinary Clinical Research Career Development Program that will teach the next generation of clinical investigators in-depth knowledge, skills, attitudes and research experiences that will allow them to communicate and work effectively with their colleagues from other disciplines. PA-07-070 Neil Powe (PI) 07/01/08-06/30/13 1.5 calendar NIH-NIDDK Direct Costs Yr 1: $577,323 Retained Organic Solutes and Clinical Outcomes in Hemodialysis The overall goal of this project is to identify retained solutes which are associated with poor outcomes in hemodialysis patents. We will then build a collaboration of experienced programs in the clinical and laboratory sciences to address this issue. 5U01DK067651 Coresh (PI) 5/15/04-04/30/09 0.90 calendar NIH/NIDDK Total Direct Cost: $309,873; 2008: $79,573 Refining Estimates of Kidney Function in the U.S. Test if equations based on serum cystatin C are superior to equations based on serum creatinine for estimating kidney function (I-131 glomerular filtration rate) in the large clinical trials (AASK and MDRD). Use these results to assay serum cystatin C in NHANES III (1988- 94) and NHANES 1999-2000 stored serum to improve national estimates of decreased kidney function and as correlates in the U.S. This grant may be converted to a U01 to facilitate coordinating with U01 to Dr. Levey on Chronic Kidney Disease Epidemiology and Estimating GFR. MM-0997-07/07 Neil Powe (PI) 10/01/06- 09/30/08 0.60 calendar AAMC/CDC Total Direct Costs: $207,316; 2007: $156,824 Establishing a Surveillance System for Chronic Kidney Disease in the US. A project to design and create a surveillance system for chronic kidney diseases in the United States. Coresh, Josef, M.D., Ph.D. (Con?t.) U01-HL-075572 Boerwinkle (PI of subcontract) 9/15/2004-6/30/09 (no cost extension) 0.30 calendar NIH/NHLBI Total Direct costs at JHU: $1,354,757; 2008: $69,689 Atherosclerosis, Plaque and CVD in Communities A collaboration of the four ARIC clinical centers and several core laboratories to examine risk factors for carotid plaque characteristics measured using magnetic resonance imaging on 2,000 participants (500 at the JHU site) T32 Coresh (PI) 7/1/05-6/30/10 0.12 calendar NIH/NHLBI (T32HL007024) Total direct cost: $2,554,907; 2008: $508,603 Cardiovascular Epidemiology Training Grant Train leaders in cardiovascular epidemiology at both the pre-doctoral (4 slots) and post-doctoral (5 slots) level. Additional work on this grant is supported by general funds and responsibilities for mentorship and teaching within other funded activities including the GCRC. PENDING KDOQI1379 Coresh (PI) 7/01/2009-6/30/12 NKF Total Direct Cost Yr 1: 144,955 1.80 calendar Complications and Prognosis of CKD in the US Population Central to the February 2002 KDOQI CKD Evaluation, classification and stratification guidelines are the issues of GFR estimation (eGFR) and its relationship to complications and Risk. This proposal will conduct rigorous data analysis in two cohorts and meta-analyze data from large population based cohorts to update our understanding of these central issues. 1 R01 HL096812-01 Coresh (PI) 07/01/09 ? 06/30/14 NIH/NHLBI Total Direct Cost Yr 1: 851,255 3.00 calendar ARIC Neurocognitive Study (ARIC-NCS) Dementia has a high prevalence in the U.S., particularly in African-Americans. The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) will add a neurocognitive assessment 24 years following the ARIC baseline exam conducted on 15,792 African-American and white residents aged 45-64. We aim to help elucidate factors underlying ethnic disparities in dementia burden and provide the scientific basis for prevention strategies by identifying vascular therapeutic targets, optimal timing for interventions and useful intermediate outcomes.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Andrea L.C. Schneider, MD, PhD
From Johns Hopkins School of Medicine (C.H.B., A.L.C.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health (A.R.S., J.C., A.L.C.S.), Baltimore, MD; University of Minnesota (A.A.), Minneapolis; Mayo Clinic (D.S.K.), Rochester, MN; and University of Mississippi Medical Center (T.H.M.), Jackson.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Alvaro Alonso, MD, PhD
From Johns Hopkins School of Medicine (C.H.B., A.L.C.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health (A.R.S., J.C., A.L.C.S.), Baltimore, MD; University of Minnesota (A.A.), Minneapolis; Mayo Clinic (D.S.K.), Rochester, MN; and University of Mississippi Medical Center (T.H.M.), Jackson.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH, N01 HC55019, 2006-2012 NIH, N01 HC95163, 2008-2015 NIH, U01 HL096902, 2010-2014
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
American Heart Association, 09SDG2280087, 2009-2013
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
David S. Knopman, MD
From Johns Hopkins School of Medicine (C.H.B., A.L.C.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health (A.R.S., J.C., A.L.C.S.), Baltimore, MD; University of Minnesota (A.A.), Minneapolis; Mayo Clinic (D.S.K.), Rochester, MN; and University of Mississippi Medical Center (T.H.M.), Jackson.
Disclosure
Scientific Advisory Boards:
1.
Consultant Bluefield project (frontotemporal demantia); Lundbeck Pharmaceuticals (Sept 2013 ongoing); DIAN study DSMB (Sept 2013 ongoing).
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Lecture, University of Pennsylvania, January 2013 (2) Lecture, St Johns Hospital, Jackson Hole Wyoming June 2013 (3) Lecture, Amer Soc Neuroradiol, San Diego CA, May 2013 (4) Lectures, Alzheimer Conference, Seoul Korea, December 2014
Editorial Boards:
1.
Neurology, Deputy Editor
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Tau Rx clinical trial
Research Support, Government Entities:
1.
NIH: R01-AG11378 ongoing, P50-AG 16574 (Mayo Alzheimer?s Disease Research Center) ongoing, U01 AG 06786 (Mayo Alzheimer Disease Patient Registry) ongoing. 1U01HL096917-01 ARIC Dementia Study. AG 037551 Chronic Kidney Disease and Cognitive functioning.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Thomas H. Mosley, PhD
From Johns Hopkins School of Medicine (C.H.B., A.L.C.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health (A.R.S., J.C., A.L.C.S.), Baltimore, MD; University of Minnesota (A.A.), Minneapolis; Mayo Clinic (D.S.K.), Rochester, MN; and University of Mississippi Medical Center (T.H.M.), Jackson.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Rebecca F. Gottesman, MD, PhD
From Johns Hopkins School of Medicine (C.H.B., A.L.C.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health (A.R.S., J.C., A.L.C.S.), Baltimore, MD; University of Minnesota (A.A.), Minneapolis; Mayo Clinic (D.S.K.), Rochester, MN; and University of Mississippi Medical Center (T.H.M.), Jackson.
Disclosure
Scientific Advisory Boards:
1.
Member of DSMB for “Sail-on” study, (PI: V. Urrutia), funded via Genentech (no compensation received).
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Cardiothoracic Surgery Symposium; funds for travel (reimbursement)
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Florbetapir isotope (18F-AV-45) provided for investigator-initiated research by Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly.
Research Support, Government Entities:
1.
National Institutes of Health/ National Institute on Aging. 1R01AG040282, Principal Investigator, 9/2011-8/2016
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
American Heart Association, Scientist Development Grant
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. Brown: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Charles Brown helped design the study, perform the statistical analysis, draft and review the manuscript, and approved the final manuscript. A. Richey Sharrett helped design the study, revise the manuscript, and approved the final manuscript. Josef Coresh provided input into the analysis, helped revise the manuscript, and approved the final manuscript. Andrea L.C. Schneider provided input into the statistical analysis, helped revise the manuscript, and approved the final manuscript. Alvaro Alonso provided input into the analysis, helped revise the manuscript, and approved the final manuscript. David S. Knopman provided input into the analysis, helped revise the manuscript, and approved the final manuscript. Thomas H. Mosley provided input into the analysis, helped revise the manuscript, and approved the final manuscript. Rebecca F. Gottesman helped design the study, provided input into the statistical analysis, helped revise the manuscript, and approved the final manuscript.

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