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Background <p>Encephalitis is an acute inflammation of the brain parenchyma, typically caused by microbial infections or autoimmune mechanisms, and represents a potentially life-threatening neurological condition affecting thousands of individuals each year in the United States. Although survivors may experience persistent neurological sequelae, long-term association of encephalitis and subsequent dementia and related diagnoses across different age groups and encephalitis etiologies remains poorly characterized. This study aimed to quantify the association between encephalitis and the risk of developing dementia and related diagnoses across age groups and encephalitis etiologies.</p> Methods <p>We conducted a retrospective cohort study using TriNetX U.S. electronic health records. We first estimated the database specific cumulative incidence and prevalence of encephalitis. Patients diagnosed with encephalitis were then compared with propensity score matched controls for the incidence of a composite outcome of dementia and related diagnoses and its individual diagnostic categories, epilepsy (positive control) and mortality. Analyses were stratified by four age groups (&lt; 20&#xa0;years, 20–40&#xa0;years, 40–60&#xa0;years and &gt; 60&#xa0;years), and encephalitis etiological subtypes (non-infectious/post-infectious inflammatory, viral, bacterial, fungal/parasitic and unspecified). To assess specificity, the encephalitis cohort was additionally compared against three comparator cohorts (sepsis, meningitis and stroke). Risk ratios and risk differences were calculated after accounting for confounding variables.</p> Results <p>The overall cumulative incidence and prevalence of encephalitis were 74.3 and 90.2 per 100,000 persons, respectively, during the 2014–2024 study period. Encephalitis was associated with an increased risk of composite of dementia and related diagnoses across all age groups. When the outcome was restricted to specific dementia codes, the association remained robust in older adults (40–60&#xa0;years and &gt; 60&#xa0;years), but was no longer evident in younger cohorts, indicating that signal in younger individuals may reflect post-encephalitic neurological sequelae. Etiology specific analysis demonstrated that non-infectious/post-infectious inflammatory encephalitis conferred the highest relative risk for dementia, followed by viral, fungal/ parasitic and unspecified encephalitis, while bacterial encephalitis showed no significant association. Compared to sepsis, meningitis and stroke, the encephalitis cohort exhibited higher risk for the composite outcome and individual diagnostic categories. Vascular dementia risk was sole exception, being higher in the stroke cohort than in encephalitis cohort, consistent with known vascular pathogenesis of post-stroke dementia. Consistent with previous studies, epilepsy risk was significantly increased across all encephalitis cohorts. Mortality was also significantly higher in the encephalitis group across all comparisons except for sepsis.</p> Conclusions <p>Encephalitis is associated with a markedly elevated long-term risk of subsequent dementia and related diagnoses in electronic health records data. These findings emphasize the need for long-term monitoring of encephalitis survivors regardless of age or etiology.</p>

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Long-term risk of dementia following encephalitis: a large-scale retrospective cohort study of electronic health records

  • 期刊论文

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  • 发表日期：

    2026年8月5日

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  • Aditi,
  • Thomas Blackwell,
  • Xiang Fang,
  • Surendra Sharma,
  • Matthew Mendoza,
  • Alan Landay,
  • Georgiy Golovko,
  • Parimal Samir

摘要

Background

Encephalitis is an acute inflammation of the brain parenchyma, typically caused by microbial infections or autoimmune mechanisms, and represents a potentially life-threatening neurological condition affecting thousands of individuals each year in the United States. Although survivors may experience persistent neurological sequelae, long-term association of encephalitis and subsequent dementia and related diagnoses across different age groups and encephalitis etiologies remains poorly characterized. This study aimed to quantify the association between encephalitis and the risk of developing dementia and related diagnoses across age groups and encephalitis etiologies.

Methods

We conducted a retrospective cohort study using TriNetX U.S. electronic health records. We first estimated the database specific cumulative incidence and prevalence of encephalitis. Patients diagnosed with encephalitis were then compared with propensity score matched controls for the incidence of a composite outcome of dementia and related diagnoses and its individual diagnostic categories, epilepsy (positive control) and mortality. Analyses were stratified by four age groups (< 20 years, 20–40 years, 40–60 years and > 60 years), and encephalitis etiological subtypes (non-infectious/post-infectious inflammatory, viral, bacterial, fungal/parasitic and unspecified). To assess specificity, the encephalitis cohort was additionally compared against three comparator cohorts (sepsis, meningitis and stroke). Risk ratios and risk differences were calculated after accounting for confounding variables.

Results

The overall cumulative incidence and prevalence of encephalitis were 74.3 and 90.2 per 100,000 persons, respectively, during the 2014–2024 study period. Encephalitis was associated with an increased risk of composite of dementia and related diagnoses across all age groups. When the outcome was restricted to specific dementia codes, the association remained robust in older adults (40–60 years and > 60 years), but was no longer evident in younger cohorts, indicating that signal in younger individuals may reflect post-encephalitic neurological sequelae. Etiology specific analysis demonstrated that non-infectious/post-infectious inflammatory encephalitis conferred the highest relative risk for dementia, followed by viral, fungal/ parasitic and unspecified encephalitis, while bacterial encephalitis showed no significant association. Compared to sepsis, meningitis and stroke, the encephalitis cohort exhibited higher risk for the composite outcome and individual diagnostic categories. Vascular dementia risk was sole exception, being higher in the stroke cohort than in encephalitis cohort, consistent with known vascular pathogenesis of post-stroke dementia. Consistent with previous studies, epilepsy risk was significantly increased across all encephalitis cohorts. Mortality was also significantly higher in the encephalitis group across all comparisons except for sepsis.

Conclusions

Encephalitis is associated with a markedly elevated long-term risk of subsequent dementia and related diagnoses in electronic health records data. These findings emphasize the need for long-term monitoring of encephalitis survivors regardless of age or etiology.