Abstract
The aim of this study was to investigate the association between incident dementia and rates of infection-related hospital contacts. We conducted a registry- and population-based matched-cohort study of all Danish residents who were born in or before 1950, included from 1 January 2000 or their 65th birthday (whichever came later), who were alive and resided in Denmark at the start of the study, excluding those who had received a dementia diagnosis before 1 January 2000 or their 65th birthday (n = 1,712,100). A total of 129,660 people (403,744 person years) with incident dementia were matched with 297,476 people (1,918,784 person years) without dementia. Incidence rate ratios (IRRs) of infection-related hospital contacts were calculated using Poisson regression, by infection type, sex and age. The IRR for any infection-related contact in dementia was 1.5, was highest for nervous and urinary system infections and sepsis, decreased with increasing age and was higher in men. More people with than without dementia had contacts five years before the index date. Our findings show that dementia is a risk factor for infection-related hospital contacts and infections might be an early sign of dementia.
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Data availability
All of the data used in this study are derived from the Danish National and Public Health registries. These data are collected and stored by the relevant authorities and cannot be made public or accessed by unauthorized parties. Access to such data is given via standard rules and regulations of data access outlined by the Danish Data Protection Agency and Danish Health Data Authority.
Code availability
SAS software version 9.4 was used for analysis and coding relating to all of the methods used in this study. We used the procedure PROC GENMOD.
References
Rao, A., Suliman, A., Vuik, S., Aylin, P. & Darzi, A. Outcomes of dementia: systematic review and meta-analysis of hospital administrative database studies. Arch. Gerontol. Geriatr. 66, 198–204 (2016).
Phelan, E. A., Borson, S., Grothaus, L., Balch, S. & Larson, E. B. Association of incident dementia with hospitalizations. J. Am. Med. Assoc. 307, 165–172 (2012).
Natalwala, A., Potluri, R., Uppal, H. & Heun, R. Reasons for hospital admissions in dementia patients in Birmingham, UK, during 2002–2007. Dement. Geriatr. Cogn. Disord. 26, 499–505 (2008).
Mitchell, S. L. Care of patients with advanced dementia. UpToDate https://www.uptodate.com/contents/care-of-patients-with-advanced-dementia (2019).
Naumova, E. N. et al. Pneumonia and influenza hospitalizations in elderly people with dementia. J. Am. Geriatr. Soc. 57, 2192–2199 (2009).
Alpay, Y., Aykin, N., Korkmaz, P., Gulduren, H. M. & Caglan, F. C.Urinary tract infections in the geriatric patients. Pakistan J. Med. Sci. 34, 67–72 (2018).
Clegg, A., Young, J., Iliffe, S., Rikkert, M. O. & Rockwood, K. Frailty in elderly people. Lancet 381, 752–762 (2013).
Parsons, C. & van der Steen, J. T. Antimicrobial use in patients with dementia: current concerns and future recommendations. CNS Drugs 31, 433–438 (2017).
Mouton, C. P., Bazaldua, O. V., Pierce, B. & Espino, D. V. Common infections in older adults. Am. Fam. Physician 63, 257–268 (2001).
Nace, D. A., Drinka, P. J. & Crnich, C. J. Clinical uncertainties in the approach to long term care residents with possible urinary tract infection. J. Am. Med. Dir. Assoc. 15, 133–139 (2014).
Kline, K. A. & Bowdish, D. M. E. Infection in an aging population. Curr. Opin. Microbiol. 29, 63–67 (2016).
Tolppanen, A.-M. et al. Hospital admissions, outpatient visits and healthcare costs of community-dwellers with Alzheimer’s disease. Alzheimers Dement. 11, 955–963 (2015).
Albert, S. M. et al. Hospitalization and Alzheimer’s disease: results from a community-based study. J. Gerontol. A Biol. Sci. Med. Sci. 54, M267–M271 (1999).
Bernardes, C., Massano, J. & Freitas, A. Hospital admissions 2000–2014: a retrospective analysis of 288 096 events in patients with dementia. Arch. Gerontol. Geriatr. 77, 150–157 (2018).
Guijarro, R. et al. Impact of dementia on hospitalization. Neuroepidemiology 35, 101–108 (2010).
Zuliani, G. et al. Discharge diagnosis and comorbidity profile in hospitalized older patients with dementia. Int. J. Geriatr. Psychiatry 27, 313–320 (2012).
Daiello, L. A., Gardner, R., Epstein-Lubow, G., Butterfield, K. & Gravenstein, S. Association of dementia with early rehospitalization among Medicare beneficiaries. Arch. Gerontol. Geriatr. 59, 162–168 (2014).
Sampson, E. L., Blanchard, M. R., Jones, L., Tookman, A. & King, M. Dementia in the acute hospital: prospective cohort study of prevalence and mortality. Br. J. Psychiatry 195, 61–66 (2009).
Shen, H.-N., Lu, C.-L. & Li, C.-Y. Dementia increases the risks of acute organ dysfunction, severe sepsis and mortality in hospitalized older patients: a national population-based study. PLoS ONE 7, e42751 (2012).
Zhao, Y., Kuo, T.-C., Weir, S., Kramer, M. S. & Ash, A. S. Healthcare costs and utilization for Medicare beneficiaries with Alzheimer’s. BMC Health Serv. Res. 8, 108 (2008).
Draper, B., Karmel, R., Gibson, D., Peut, A. & Anderson, P. The Hospital Dementia Services Project: age differences in hospital stays for older people with and without dementia. Int. Psychogeriatrics 23, 1649–1658 (2011).
Harris, D. P., Chodosh, J., Vassar, S. D., Vickrey, B. G. & Shapiro, M. F. Primary care providers’ views of challenges and rewards of dementia care relative to other conditions. J. Am. Geriatr. Soc. 57, 2209–2216 (2009).
Hendriks, S. A. et al. End-of-life treatment decisions in nursing home residents dying with dementia in the Netherlands. Int. J. Geriatr. Psychiatry 32, e43–e49 (2017).
Allers, K. & Hoffmann, F. Mortality and hospitalization at the end of life in newly admitted nursing home residents with and without dementia. Soc. Psychiatry Psychiatr. Epidemiol. 53, 833–839 (2018).
Kitazawa, M., Oddo, S., Yamasaki, T. R., Green, K. N. & LaFerla, F. M. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer’s disease. J. Neurosci. 25, 8843–8853 (2005).
Dunn, N., Mullee, M., Perry, V. H. & Holmes, C.Association between dementia and infectious disease: evidence from a case-control study.Alzheimer Dis. Assoc. Disord. 19, 91–94 (2005).
Balin, B. J. & Hudson, A. P. Herpes viruses and Alzheimer’s disease: new evidence in the debate. Lancet Neurol. 17, 839–841 (2018).
Holmes, C. Review: systemic inflammation and Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 39, 51–68 (2013).
Maheshwari, P. & Eslick, G. D. Bacterial infection and Alzheimer’s disease: a meta-analysis. J. Alzheimers Dis. 43, 957–966 (2015).
Shindler-Itskovitch, T., Ravona-Springer, R., Leibovitz, A. & Muhsen, K. A systematic review and meta-analysis of the association between Helicobacter pylori infection and dementia. J. Alzheimers Dis. 52, 1431–1442 (2016).
Phung, T. K. T. et al. Validity of dementia diagnoses in the Danish hospital registers. Dement. Geriatr. Cogn. Disord. 24, 220–228 (2007).
Zakarias, J. K. et al. Geographical variation in the diagnostic rate and quality of dementia diagnoses.J. Alzheimers Dis. 69, 513–520 (2019).
Bauer, K., Schwarzkopf, L., Graessel, E. & Holle, R. A claims data-based comparison of comorbidity in individuals with and without dementia. BMC Geriatr. 14, 10 (2014).
Taudorf, L. et al. Declining incidence of dementia: a national registry-based study over 20 years. Alzheimers Dement. 15, 1383–1391 (2019).
National Research Strategy on Dementia 2025 (Danish Health Authority, 2018); https://www.sst.dk/-/media/Udgivelser/2018/National-Research-Strategy-on-Dementia-2025_Final.ashx
Bebe, A. et al. Exploring the concurrent validity of the nationwide assessment of permanent nursing home residence in Denmark—a cross-sectional data analysis using two administrative registries. BMC Health Serv. Res. 17, 607 (2017).
Boisen, A. B., Dalager-Pedersen, M., Søgaard, M., Mortensen, R. & Thomsen, R. W. Relationship between death and infections among patients hospitalized in internal medicine departments: a prevalence and validation study. Am. J. Infect. Control 42, 506–510 (2014).
Erlangsen, A. & Fedyszyn, I. Danish nationwide registers for public health and health-related research. Scand. J. Public Health 43, 333–339 (2015).
Thygesen, L. C., Daasnes, C., Thaulow, I. & Brønnum-Hansen, H. Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand. J. Public Health 39, 12–16 (2011).
Schmidt, M. et al. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin. Epidemiol. 7, 449–490 (2015).
Mors, O., Perto, G. P. & Mortensen, P. B. The Danish Psychiatric Central Research Register. Scand. J. Public Health 39, 54–57 (2011).
Wallach Kildemoes, H., Toft Sørensen, H. & Hallas, J. The Danish National Prescription Registry. Scand. J. Public Health 39, 38–41 (2011).
Brusselaers, N. & Lagergren, J. The Charlson comorbidity index in registry-based research. Methods Inf. Med. 56, 401–406 (2017).
Ribe, A. R. et al. Thirty-day mortality after infection among persons with severe mental illness: a population-based cohort study in Denmark. Am. J. Psychiatry 172, 776–783 (2015).
Nielsen, P. R., Benros, M. E. & Mortensen, P. B. Hospital contacts with infection and risk of schizophrenia: a population-based cohort study with linkage of Danish national registers. Schizophr. Bull. 40, 1526–1532 (2014).
Data for research. Statistics Denmark https://www.dst.dk/en/TilSalg/Forskningsservice (2020).
Acknowledgements
The Danish Dementia Research Centre is supported by the Danish Ministry of Health, which was not involved in any phase of this study (design or conduct; collection, management, analysis or interpretation of the data; preparation, review or approval of the manuscript; or decision to submit the manuscript for publication).
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J.J., G.W. and N.F.-M. conceived of the study concept and performed the literature review. All authors designed the study. J.J. and N.F.-M. prepared and defined the data related to the infection codes. J.J. and T.M.L. performed the statistical analyses. J.J. wrote the manuscript as outlined by J.J. and G.W. All authors contributed equally to data interpretation and critical review of the manuscript.
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Janbek, J., Frimodt-Møller, N., Laursen, T.M. et al. Dementia identified as a risk factor for infection-related hospital contacts in a national, population-based and longitudinal matched-cohort study. Nat Aging 1, 226–233 (2021). https://doi.org/10.1038/s43587-020-00024-0
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DOI: https://doi.org/10.1038/s43587-020-00024-0
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