And vaccination against shingles was associated with lower subsequent risk for vascular dementia or Alzheimer’s disease.

Chronic, low-grade infection of the brain has been linked to excess risk for various forms of dementia, including vascular dementia and Alzheimer’s disease (AD). Herpesviruses are prime suspects, because they are neurotropic and cause lifelong infections. Herpes simplex 1 and 2 viruses (NEJM JW Gen Med Jun 15 2020 and Sci Adv 2020; 6: eaay8828) and human cytomegalovirus (NEJM JW Gen Med Sep 1 2006 and J Am Geriatr Soc 2006; 54: 1046-1054) have been linked to dementia. Two new studies incriminate another herpesvirus, varicella-zoster virus (VZV).

Nearly 150,000 people in three prospective observational studies periodically completed questionnaires to assess subjective cognitive decline. Participants’ previous shingles episodes were validated and recorded. During longer than a decade of observation, shingles was a significant predictor of dementia, with adjusted relative risks ranging from 1.14 to 1.34, depending on the cohort, patient sex and duration of observation.

In a US study of electronic health records of 200,000 people, risk for developing dementia was evaluated in patients who received either the original live-virus VZV vaccine (Zostavax), the current recombinant vaccine (Shingrix), an influenza vaccine or the tetanus-diphtheria-pertussis (Tdap) vaccine. A multivariable analysis showed that in the six years following VZV immunisation, patients had about 20% lower risk for developing vascular dementia or AD than did patients who received flu or Tdap vaccines only. 

Comment: These studies are consistent with a growing literature that supports a role for chronic neuroinflammation generated by chronic infection (particularly by herpesviruses) in some cases of vascular dementia and AD. Herpesviruses can cause vascular pathology directly and can stimulate production of both amyloid-beta and tau, two molecules that are central to AD pathology.

Anthony L. Komaroff, MD, Professor of Medicine, Harvard Medical School, Boston, USA.

Yeh T-S, et al. Herpes zoster and long-term risk of subjective cognitive decline. Alzheimers Res Ther 2024; 16: 180.
Taquet M, et al. The recombinant shingles vaccine is associated with lower risk of dementia. Nat Med 2024; e-pub (https://doi. org/10.1038/s41591-024-03201-5).

The summary is taken from the following Journal Watch titles: General Medicine, Neurology, Hospital Medicine