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Bacterial pneumonia and subsequent dementia risk: A nationwide cohort study

https://doi.org/10.1016/j.bbi.2022.04.002Get rights and content

Highlights

  • Higher risk by 2.83-fold of dementia was found in patients with bacterial pneumonia.

  • The higher risk was found in patients with bacterial pneumonia for Alzheimer’s disease (AD), vascular dementia (VaD), and unspecified dementia.

  • Pneumonia caused by majority of pathogens were associated with higher risks of VaD and unspecified dementia.

  • Pneumonia caused by Haemophilus was associated with an increased risk of AD.

  • A dose–response association was found between the number of hospitalizations and risk of VaD.

Abstract

Background

Bacterial pneumonia is associated with an increased risk of dementia. However, the association between different pathogens of bacterial pneumonia and the risk of dementia remains unclear.

Methods

Using the Taiwan National Health Insurance Research Database, we recruited 11,712 patients with bacterial pneumonia and 11,120 controls between 1997 and 2012 and followed them up until the end of 2013. A diagnosis of dementia, Alzheimer’s disease (AD), vascular dementia (VaD), and unspecified dementia were identified during the follow-up period. Cox regression analyses were performed with adjustments for confounders. Sensitivity analysis was conducted to exclude patients with prodromal dementia.

Results

Patients with bacterial pneumonia were more likely to develop dementia (hazard ratio [HR]: 2.83, 95% confidence interval [CI]: 2.53–3.18), AD (HR: 2.44, 95% CI: 1.65–3.61), VaD (HR: 4.15, 95% CI: 3.20–5.38), and unspecified dementia (HR: 2.62, 95% CI: 2.29–3.00) compared with controls after adjusting for potential confounders. Subgroup pathogen analyses showed that the HR of AD was 3.85 (1.66–8.96) for Hemophilus, and the HR of VaD was 5.40 for Staphylococcus. The risks of dementia and VaD were associated with repeated hospitalization due to bacterial pneumonia in a dose-dependent manner. Sensitivity analyses after exclusion of the first three years or first five years of observation and after exclusion case enrollment before 2010 or 2008 showed consistent findings.

Conclusion

Different pathogens are associated with different risks of AD, VaD, and unspecified dementia. Further studies are necessary to investigate the underlying mechanisms of bacterial pneumonia and dementia.

Introduction

Dementia is a chronic neurodegenerative disease characterized by progressive global cognitive dysfunction and loss of independence (Livingston et al., 2020). Dementia is the fifth leading cause of death worldwide, and the number of people with dementia is expected to reach 50 million by 2050 (Nichols et al., 2019). To date, the underlying mechanisms contributing to dementia are not well understood; therefore, reduction of risk factors and early diagnosis are important for the management of dementia (Livingston et al., 2020).

Community-acquired pneumonia is a major source of morbidity and mortality, with over a million hospitalizations in the United States each year (ATSTPF, 2022). This causes a huge burden on the economy, health system, and caregivers (ATSTPF, 2022). The majority of previous follow-up studies aimed to examine in-hospital or short-term outcomes (less than one year) on mortality and disability (Arnold et al., 2020, Ramirez et al., 2017, Daniel et al., 2016). Little is known about the long-term cognitive consequences among patients who survive hospitalization for pneumonia. Emerging data from epidemiological studies have shown an association between bacterial pneumonia and an increased risk of subsequent dementia (Muzambi et al., 2021, Sipilä et al., 2021, Mawanda et al., 2016, Tate et al., 2014, Shah et al., 2013). In a large nationally representative sample of US veterans (age ≥ 56 years), extra central nervous system bacterial infections, such as pneumonia, were associated with a 1.1-fold increased risk of dementia (Mawanda et al., 2016). A recent meta-analysis (11 case-control studies with 389 CE cases and 351 controls) reported that Chlamydia pneumoniae infection was associated with a 4.39-fold higher risk of developing Alzheimer’s disease (AD) (Ou et al., 2020).

However, several issues need to be considered in the association between bacterial pneumonia and dementia. First, previous studies reporting the association between AD and Chlamydia pneumoniae infection are mainly derived from a cross-sectional design, limiting the causality (Ou et al., 2020). Furthermore, whether the effect of more commonly specific microbes such as Streptococcus pneumoniae and Staphylococcus aureus poses a variable risk on the development of dementia is unknown. Third, ethnic differences have been observed in dementia risk (Shiekh et al., 2021). The association between bacterial pneumonia and the risk of dementia in non-Western populations is scarce. Fourth, previous studies reported that the average duration of developing dementia after pneumonia was two years (Shah et al., 2013), which may be too short to exclude occult dementia at the time of pneumonia. Moreover, sensitivity analyses of exclusion of prodromal dementia may also be important to preclude reverse causation. Fifth, the effect of pneumonia was mainly focused on the risk of dementia (Mawanda et al., 2016, Tate et al., 2014, Shah et al., 2013) and AD (Ou et al., 2020). However, it is unknown for vascular dementia (VaD).

To address the above gaps, we used a dataset from the National Health Insurance Research Database (NHIRD) in Taiwan to investigate the risk of dementia after a diagnosis of bacterial pneumonia. We conducted a longitudinal study with a large sample of community-dwelling adults. Furthermore, we examined whether the pathogens of bacterial pneumonia were associated with different risks for different types of dementia.

Section snippets

Data acquisition

Taiwan’s National Health Insurance, a mandatory universal health insurance program, offers comprehensive medical care coverage to all Taiwanese residents (>23 million people). The Taiwan National Health Research Institute audits and releases the Taiwan NHIRD for scientific studies (Huang et al., 2021, Liang et al., 2020). Comprehensive information on insured individuals is included in the database, such as demographic data, clinical visit dates, disease diagnoses, inpatient procedures, and

Characteristics of the study participants

A total of 11,712 patients with bacterial pneumonia and 117,120 controls were enrolled in our study (Table 1). The mean age at enrollment was 68.07 ± 11.62 in patients with bacterial pneumonia and 68.00 ± 11.65 in controls. The two groups did not differ in age at enrollment, proportion of males, dementia-related comorbidities, level of urbanization, and income-related insured amount. Patients with bacterial pneumonia had a higher mean CCI score than controls (4.02 ± 2.66 vs. 2.84 ± 2.40,

Discussion

The present study revealed that: (a) after a diagnosis of bacterial pneumonia, the risk of dementia was 2.83-fold higher than controls without bacterial pneumonia; (b) these patients also had significantly higher risks of AD, VaD, and unspecified dementia; (c) the majority of pathogens were associated with higher risks of VaD and unspecified dementia, while only Haemophilus was associated with an increased risk of AD; (d) a dose–response association between the number of hospitalizations and

Conclusion

The present study using a large nationwide dataset revealed that patients with bacterial pneumonia have a 2.83-fold risk of developing dementia compared with non-bacterial pneumonia controls. Different pathogens are associated with different risks of AD, VaD, and unspecified dementia. Prevention or timely intervention for bacterial pneumonia might reduce the risk of subsequent dementia among older adults. Further research is recommended to elucidate the mechanisms underlying this association.

Funding Source

The study was supported by grant from Taipei Veterans General Hospital (V106B-020, V107B-010, V107C-181, V108B-012, V110C-025, V110B-002), Kaohsiung Veterans General Hospital (KGVGH-110–051, VGHKS-109–070), Yen Tjing Ling Medical Foundation (CI-109–21, CI-109–22, CI-110–30) and Ministry of Science and Technology, Taiwan (107–2314-B-075–063-MY3, 108–2314-B-075–037, MOST-109–2314-B-075B-001-MY2). The funding source had no role in any process of our study.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

None.

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