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<jats:p>To examine the association between hospitalization, critical illness, and infection occurring during middle\u2010 and late\u2010life and structural brain abnormalities in older adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Prospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Atherosclerosis Risk in Communities (ARIC) Study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>A community sample of adults who were 44 to 66 years of age at study baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>\n                      Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including\n                      <jats:italic>International Classification of Diseases, Ninth Revision<\/jats:italic>\n                      , codes) on all participants over a 24\u2010year surveillance period. Subsequently, a subset of participants underwent 3\u2010Tesla 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)).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 1,689 participants included (mean age at MRI 76\u00b15), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate\u2010adjusted regression, hospitalization was associated with 0.12\u2013standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00\u20130.24) and poorer white matter microstructural integrity (0.17\u2010SD lower FA, 95% CI=\u20130.27 to \u20130.06; 0.16\u2010SD greater MD, 95% CI=0.07\u20130.25) than no hospitalization. There was a dose\u2010dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2010trends \u2264.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (\u20131.64 cm\n                      <jats:sup>3<\/jats:sup>\n                      , 95% CI=\u20133.16 to \u20130.12); major infection was associated with smaller AD signature region (\u20131.28 cm\n                      <jats:sup>3<\/jats:sup>\n                      , 95% CI=\u20132.21 to \u20130.35) and larger ventricular volume (3.79 cm\n                      <jats:sup>3<\/jats:sup>\n                      , 95% CI= 0.81\u20136.77).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Whereas all\u2010cause 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.<\/jats:p>\n                  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