Investigation of Infectious Disease Associations with Cognitive Impairment using Electronic Medical Records

Although infection-driven neurocognitive deterioration has been postulated for decades, definitive population-level evidence is scarce. We therefore undertook a multi-center electronic health record study to quantify the association between six clinically important infections—Herpes simplex virus (HSV), syphilis, Chlamydia trachomatis, coronavirus disease 2019 (COVID-19), cytomegalovirus (CMV), and human immunodeficiency virus (HIV)—and subsequent cognitive impairment. On June 12, 2025, we queried the global TriNetX network for encounters containing both diagnostic codes (ICD10-CM) and confirming laboratory results (LOINC) for each pathogen, constructing sex stratified cohorts of up to 1,932,669 exposed patients that maximized diagnostic certainty. A comparator cohort was derived from encounters coded Z00 (routine examination) after excluding any of the target infections by diagnosis or laboratory evidence totaling up to 131,5694 control patients. Baseline demographic characteristics were assessed using TriNetX’s Compare Outcomes module, which balanced age, race, and sex distributions through propensity score matching before survival analysis. Kaplan–Meier curves and matched measures of association were then used to estimate infection-specific hazard ratios for cognitive decline given a five-year follow-up window. Across pathogens, we observed heterogeneous, infection-dependent elevation in risk, indicating that certain infections may be nontrivial contributors to neurodegenerative trajectories. While there are inherent limitations to utilizing real-world data such as lack of biomarkers and neuropsychological testing as well as potential outcome misclassification and left censoring of comorbidities due to structural features of TriNetX, our results imply that renewed investment in sexually transmitted infection screening, treatment completion, and partner notification programs could be feasible targets to lessen the impact of cognitive impairment.

Name thesis:degree_name

Biochemistry and Molecular Biology (Masters)

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2025

Author dc:creator

• Littleton, Tehya Marie

Advisor dc:contributor.advisor

• Golovko, George (gegolovk@utmb.edu)

Committee members dc:contributor.committeemember

• Kamil Khanipov (kakhanip@utmb.edu)
• Cristiana Rastellini (ccrastel@utmb.edu)

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12712

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12712