Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults

Keenan A. Walker; Rebecca F. Gottesman; Aozhou Wu; David S. Knopman; Thomas H. Mosley; Alvaro Alonso; Anna Kucharska-Newton; Charles H. Brown

doi:10.1111/jgs.15470

Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults

Keenan A. Walker, Rebecca F. Gottesman, Aozhou Wu, David S. Knopman, Thomas H. Mosley, Alvaro Alonso, Anna Kucharska-Newton, Charles H. Brown

Epidemiology & Environmental Health

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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.

Original language	English
Pages (from-to)	1919-1926
Number of pages	8
Journal	Journal of the American Geriatrics Society
Volume	66
Issue number	10
DOIs	https://doi.org/10.1111/jgs.15470
State	Published - Oct 2018

Bibliographical note

Publisher Copyright:
© 2018, Copyright the Author Journal compilation © 2018, The American Geriatrics Society

Funding

Financial Disclosure: This work was supported by National Heart, Lung, and Blood Institute (NHLBI) Contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HSN2682 01100009C, HHSN268201100010C, HHSN2682011000 11C, and HHSN268201100012C. The NHLBI and National Institute of Neurological Disorders and Stroke supported neurocognitive data collection (Grants U01 HL096812, HL096814, HL096899, HL096902, HL096917), with and the NHLBI funded previous brain MRI (Grant R01-HL70825). This study was also supported by grants from the National Institute on Aging (AG027668 to KAW; AG052573 to RFG). The National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) provided support for the statistical analysis (Grant 1UL1TR001079). Conflict of Interest: RFG serves as Associate Editor for Neurology and receives research support from the NIH. DSK serves on a Data Safety Monitoring Board for the Dominantly Inherited Alzheimer Network Study; is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California; and receives research support from the NIH. CB has consulted for and participates in a data-sharing agreement with Medtronic.

Funders	Funder number
Eli Lilly pharmaceuticals
National Institutes of Health (NIH)	1UL1TR001079
National Institute on Aging	AG027668, K76AG057020, AG052573
National Heart, Lung, and Blood Institute (NHLBI)	HHSN268201100008C
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	HL096814, HL096902, HL096917, R01-HL70825, U01 HL096812, HL096899
National Center for Research Resources
Biogen IDEC
University of Southern California
National Center for Advancing Translational Sciences (NCATS)

Keywords

Alzheimer's disease
dementia
magnetic resonance imaging
risk factor

ASJC Scopus subject areas

Geriatrics and Gerontology

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10.1111/jgs.15470

Cite this

@article{a5bc2db299194e97bf97d5fab7746163,

title = "Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults",

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.",

keywords = "Alzheimer's disease, dementia, magnetic resonance imaging, risk factor",

author = "Walker, \{Keenan A.\} and Gottesman, \{Rebecca F.\} and Aozhou Wu and Knopman, \{David S.\} and Mosley, \{Thomas H.\} and Alvaro Alonso and Anna Kucharska-Newton and Brown, \{Charles H.\}",

note = "Publisher Copyright: {\textcopyright} 2018, Copyright the Author Journal compilation {\textcopyright} 2018, The American Geriatrics Society",

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month = oct,

doi = "10.1111/jgs.15470",

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AU - Walker, Keenan A.

AU - Gottesman, Rebecca F.

AU - Wu, Aozhou

AU - Knopman, David S.

AU - Mosley, Thomas H.

AU - Alonso, Alvaro

AU - Kucharska-Newton, Anna

AU - Brown, Charles H.

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - dementia

KW - magnetic resonance imaging

KW - risk factor

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Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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