Antivirals to Treat Herpes Infection May Decrease Risk of Dementia

According to a review of a lifetime of research literature, the herpes simplex virus type 1 is associated with an increased risk of Alzheimer’s disease. Despite this increased risk, new data show that antiviral drug regimens to treat the infection may substantially reduce the risk of senile dementia in patients with severe herpes infections. Findings from this review were published in Frontiers in Ageing Neuroscience.

“The most important finding is that anti-herpes antivirals are protective against the development of Alzheimer’s disease,” Ruth F. Itzhaki, MSc, PhD, of the University of Manchester, told Contagion® when asked about the clinical implications of her findings. “[Therefore,] a clinical trial is warranted to find out if anti-herpes antivirals are effective in preventing further deterioration in patients with mild Alzheimer’s disease.”

According to the data presented by Dr. Itzhaki, the majority of the population is infected with herpes simplex virus type 1 by the time they reach 70 years of age. In middle age, the virus travels to the brain where it remains latent, followed by intermittent reactivation and major inflammation in brain tissue. Carriers of the Apolipoprotein-E (APOE)-ε4 protein may be at particular risk for expedited Alzheimer’s disease development in the presence of herpes infection, because of the protein’s known associated risk with dementia.

The literature consistently demonstrate that viral DNA are frequently located within Alzheimer’s disease plaques, and beta-amyloid (Aβ), the main plaque component, “accumulates in herpes simplex virus type 1-infected cell cultures.” Additionally, the tau (P-tau) protein in neurofibrillary tangles also accumulate in herpes simplex virus type 1-infected cell cultures, lending to the theory of an association between herpes and Alzheimer’s disease genesis.

Other studies demonstrate that there may exist a role of human herpes virus type 6 and 7 in Alzheimer’s disease development and/or progression. In a recently published study, the risk of senile dementia was 2.56-fold greater in patients with herpes simplex virus type 1 and herpes simplex virus type 2 patients compared with healthy controls during a 10-year period. An approximate 10-fold reduction in senile dementia risk was found in another study of patients who were treated with several different anti-herpes agents compared with untreated patients.

Treatment of herpes simplex virus type 1 typically relies on the routine use of several antivirals, either as monotherapy or combination therapy. Acyclovir (ACV), for instance, inhibits viral DNA replication and is frequently used intravenously against herpes simplex virus type 1. According to the literature compiled by Dr. Itzhaki, the formation of P-tau depends on the replication of viral DNA, suggesting that antivirals may indeed reduce the risk of Alzheimer’s disease. “Clearly, the types of antiviral which might be used for treating Alzheimer’s disease should be carefully chosen, especially if combined with an anti-inflammatory agent, as well as the duration of treatment and stage at which their usage would most effective,” Dr. Itzhaki explained in her paper. “Even if the effects were merely a delay in onset of the disease, this would still be enormously beneficial for patients, careers and the economy.”

Reduction of inflammatory components involved in herpes may be partly attributed to the reduced risk of Alzheimer’s disease in patients treated with antiviral regimens; however, Dr. Itzhaki mentions that the exact mechanisms associated with the reduced risk are currently unknown. The currently available data do, however, suggest that antivirals, as well as anti-inflammatory medications, may be important combination therapy strategies in herpes-infected patients, particularly those who have an increased risk for Alzheimer’s disease.

“The detailed mechanisms of the action of herpes simplex virus type 1 in leading to Alzheimer’s disease are still unclear,” Dr. Itzhaki added. “Another point is that the Taiwan epidemiological studies were restricted to subjects with severe herpes simplex virus type 1 symptoms. They do very probably apply also to those with mild symptoms, and to asymptomatic people, but no investigations have yet been done on such subjects.”

Reference:

Itzhaki RF. Corroboration of a major role for herpes simplex virus type 1 in Alzheimer's disease [published online October 18, 2018]. Frontiers in Ageing Neuroscience.