Background Accumulating evidence implicates infectious pathogens as triggers of immune–inflammatory processes that contribute to neurodegeneration. Inflammation in both the brain and peripheral circulation is recognized as a critical factor in the development and progression of cognitive decline and neurodegenerative disorders, including Alzheimer's disease. Objective This retrospective case-control study investigated the association between cognitive impairment and presence of serum antibodies to seven pathogens in older adults. Methods One hundred sixty-five participants aged ≥ 65 years from the Panama Aging Research Initiative Health Disparities (PARI-HD) study were evaluated. Presence of IgG antibodies against Toxoplasma gondii , Herpes Simplex Virus Type 1 (HSV-1), Human Cytomegalovirus (HCMV), Helicobacter pylori, Chlamydia pneumoniae, Treponema pallidum , and Trypanosoma cruzi was measured. Participant demographics, inflammatory biomarkers and cognitive-functional factors were analyzed for associations with single/multiple pathogen-specific antibodies reactivity using multivariable regression models. Results Only C. pneumoniae seropositivity was significantly different between cognitively unimpaired and impaired groups (p = 0.02) and increasing TNF-α levels were directly associated with C. pneumoniae seropositivity (OR = 2.08, CI 95% 1.0–4.1, p = 0.04). Additionally, cumulative exposure to infectious agents increased the likelihood of cognitive impairment (OR = 1.51, CI 95% 1.01–2.26, p = 0.04) and was associated with slower processing speed as measured by TMT A test (OR = 17.43, CI 95% 2.32–32.53, p = 0.02). Notably, the presence of C. pneumoniae in multiple pathogen interactions further raised the likelihood of cognitive impairment (OR = 4.07, CI 95% 1.24–13.36, p = 0.03). Conclusions These results enhance our understanding of cognitive impairment in a Hispanic population and underscore the need for further studies on the role of C. pneumoniae and multi-pathogen infection in Alzheimer's disease.
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