Background: Herpes Simplex Virus (HSV) infection has been proposed as a possible risk factor of Alzheimer's Disease notably because it is neurotropic, ubiquitous in the general population and able to establish lifelong latency in the host. A higher prevalence of Helicobacter pylori (Hp) infection was also found in Alzheimer's disease or MCI patients. We investigated whether HSV or Hp infection was a risk factor for developing dementia over a 14 years period. Methods: Sera from 512 elderly initially free of dementia included in the PAQUID cohort and followed for 14 years were analysed. Subjects were considered as infected by HSV if the presence of anti-HSV IgG or IgM antibodies was detected. Subjects were considered as infected by Hp if immunoblot assay was positive. Cox proportional hazard models were used to study the risk of developing dementia. Results: During the follow-up, 97 incident cases of dementia were diagnosed. Controlled for age, gender, educational level, baseline MMSE and Apolipoprotein E4 (APOE4) status, IgM-positive subjects showed a significant higher risk of developing dementia (HR= 2.06; 95% CI [1.15 - 3.69]; p<0.015), although no significant increased risk was observed in IgG-positive subjects (HR=1.77; 95%CI [0.87 - 3.59]; p<0.11). Subjects infected with Hp also showed a higher risk of developing dementia (HR= 1.61; 95% CI [0.99 - 2.61]; p<0.06). Conclusions: Reactivation of HSV seropositivity is highly correlated with incident AD. Hp infection also tends to increase the risk of developing dementia. Chronic infections may therefore be contributive to the neural tissue damage observed in neurodegenerative diseases.
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