Objectives: Severe infections, often requiring ICU admission, have been associated with persistent cognitive dysfunction. Less severe infections are more common and whether they are associated with an increased risk of dementia is unclear. We determined the association of pneumonia hospitalization with risk of dementia in well-functioning older adults.
Design: Secondary analysis of a randomized multicenter trial to determine the effect of Gingko biloba on incident dementia.
Setting: Five academic medical centers in the United States.
Subjects: Healthy community volunteers (n = 3,069) with a median follow-up of 6.1 years.
Measurement and Main Results: We identified pneumonia hospitalizations using International Classification of Diseases, 9th Edition—Coding Manual codes and validated them in a subset. Less than 3% of pneumonia cases necessitated ICU admission, mechanical ventilation, or vasopressor support. Dementia was adjudicated based on neuropsychological evaluation, neurological examination, and MRI. Two hundred twenty-one participants (7.2%) incurred at least one hospitalization with pneumonia (mean time to pneumonia = 3.5 yr). Of these, dementia was developed in 38 (17%) after pneumonia, with half of these cases occurring 2 years after the pneumonia hospitalization. Hospitalization with pneumonia was associated with increased risk of time to dementia diagnosis (unadjusted hazard ratio = 2.3; CI, 1.6–3.2; p < 0.0001). The association remained significant when adjusted for age, sex, race, study site, education, and baseline mini-mental status examination (hazard ratio = 1.9; CI, 1.4–2.8; p < 0.0001). Results were unchanged when additionally adjusted for smoking, hypertension, diabetes, heart disease, and preinfection functional status. Results were similar using propensity analysis where participants with pneumonia were matched to those without pneumonia based on age, probability of developing pneumonia, and similar trajectories of cognitive and physical function prior to pneumonia (adjusted prevalence rates, 91.7 vs 65 cases per 1,000 person-years; adjusted prevalence rate ratio = 1.6; CI, 1.06–2.7; p = 0.03). Sensitivity analyses showed that the higher risk also occurred among those hospitalized with other infections.
Conclusion: Hospitalization with pneumonia is associated with increased risk of dementia.
1Department of Acute and Tertiary Care, School of Nursing, University of Pittsburgh, Pittsburgh, PA.
2Department of Neurology, University of Pittsburgh, Pittsburgh, PA.
3Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
4National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health, Bethesda, MD.
5The Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, University of Pittsburgh, Pittsburgh, PA.
6Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA.
7Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA.
8Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
9Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.
10Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
11Department of Biostatistics, University of Washington, Seattle, WA.
12School of Medicine, University of Virginia, Charlottesville, VA.
* See also p. 1282.
Dr. Tate had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The GEM Study Investigators are listed in Appendix 1.
Gingko Effect on Memory study was supported by grant U01 AT000162 from the National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements and National Institute on Aging; National Heart, Lung, and Blood Institute; University of Pittsburgh Alzheimer’s Disease Research Center (P50AG05133); Roena Kulynych Center for Memory and Cognition Research; Wake Forest University School of Medicine; and National Institute of Neurological Disorders and Stroke.
Dr. Tate is funded by T-32 (MH19986—principal investigator [PI] Reynolds). Dr. Tate’s institution received grant support from the National Institute of Mental Health (T32-MH19986—PI Reynolds). Dr. Tate received support for article research from the National Institutes of Health (NIH) (T-32 MH19986—PI Reynolds). Dr. Snitz is supported by National Institute on Aging (NIA 5K23AG038479). Dr. Snitz’s institution received grant support from the NIH. Dr. Snitz received support for article research from the NIH. Dr. Nahin is employed by the NIH. Dr. Lopez consulted for Grifols, Lilly, and Baxter. Dr. Lopez’s institution received grant support (NIA: P50 AG05133-27). Dr. Ives’ institution received grant support and support for travel from National Center for Complementary and Alternative Medicine/NIH. Dr. Ives is employed by the University of Pittsburgh and received support for article research from the NIH. Dr. Fitzpatrick and her institution received grant support from the NIH and Centers for Disease Control and Prevention (CDC). Dr. Fitzpatrick received support for article research from the NIH and CDC. Dr. Williamson’s institution received grant support and support for travel from the NIH. Dr. Williamson received support for article research from the NIH. Dr. Arnold and her institution received grant support from the NIH. Dr. Arnold received support for travel and support for article research from the NIH. Dr. DeKosky’s institution received grant support from the NIH, support for travel from the NIH, and the active Gingko Extract and the placebo tablets for the original Gingko Effect on Memory trial from Schwabe Pharamaceuticals. Dr. DeKosky received support for article research from the NIH. Dr. Yende’s institution received grant support from the NIH. Dr. Yende received support for article research from the NIH and National Institute of General Medical Sciences (K23GM083215). The remaining authors have disclosed that they do not have any potential conflicts of interest.
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