TY - JOUR
T1 - Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults
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.
N1 - Funding Information:
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).
Funding Information:
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.
Publisher Copyright:
© 2018, Copyright the Author Journal compilation © 2018, The American Geriatrics Society
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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U2 - 10.1111/jgs.15470
DO - 10.1111/jgs.15470
M3 - Article
C2 - 30251380
AN - SCOPUS:85053818371
SN - 0002-8614
VL - 66
SP - 1919
EP - 1926
JO - Journal of the American Geriatrics Society
JF - Journal of the American Geriatrics Society
IS - 10
ER -