Table 5.

Summary of the studies of association of the infection and ADRD

Study	Study design	Findings
Pisa, 2015 [70]	Postmortem	Immunohistochemical analyses of the brain tissue from AD patients showed intracellular fungal material. Similar staining did not reveal fungal material in the control tissue of the patients without AD.
Maheshwari, 2015 [72]	Meta-analysis	Ten-fold increase in risk of occurrence of AD with presence of spirochetal infection (OR: 10.61; 95% CI: 3.38–33.29). Five-fold increase in rick of occurrence of AD with presence of Chlamydophila infection (OR: 5.66; 95% CI: 1.83–17.51)
Pisa, 2016 [73]	Postmortem	Presence of fungal proteins, enolase and β-tubulin, and polysaccharide chitin in tissue sample from AD patients
Alonso, 2017 [74]	Postmortem	Next-generation sequencing revealed fungal species Alternaria, Botrytis, Candida, Cladosporium, and Malassezia in the tissue of entorhinal cortex and hippocampus of the patient with ADRD
Tzeng, 2018 [71]	Retrospective cohort study	Adjusted HR of 2.564 (95% CI: 2.351–2.795, p < 0.001) for development of ADRD in HSV-infected cohort versus non-HSV cohort. Treatment with anti-herpetic medication showed reduction of dementia development (adjusted HR = 0.092 [95% CI 0.079–0.108], p < 0.001).

AD, Alzheimer’s disease; HSV, herpes simplex virus; OR, odds ratio; HR, hazard ratio; CI, confidence intervals.