Mounting evidence points to a connection between dementia and common herpes virus infections, particularly herpes simplex virus type 1 (HSV-1), which causes cold sores, and varicella zoster virus (VZV), the cause of chickenpox and shingles.<\/p>\n
Multiple studies have shown that individuals with a history of these infections face a higher risk for dementia, including Alzheimer\u2019s disease (AD). What was once a fringe hypothesis has gained traction, as a growing body of research points to these viruses as major factors in Alzheimer\u2019s and other dementias.<\/p>\n
\u201cThere is now quite a lot of evidence obtained by a variety of methods which suggests that this virus is really a major factor in Alzheimer\u2019s disease. And the weight of the evidence supports a causal role,\u201d Ruth Itzhaki, MSc, PhD, visiting professor, The Oxford Institute of Population Aging, Oxford, England, told Medscape Medical News.<\/p>\n
Itzhaki was one of the first to hypothesize there was a potential connection between the herpes virus and AD and has spent much of her career investigating the link.<\/p>\n
These pathogens may act as \u201cunder-recognized drivers of neurodegeneration. They can hide in the nervous system and reactivate later in life, each flare-up potentially inflicting cumulative damage that accelerates cognitive decline,\u201d Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami told Medscape Medical News.<\/p>\n
One early clue came decades ago, when Itzhaki and colleagues discovered HSV-1 DNA in the brains of patients with AD, most notably in carriers of the apolipoprotein E epsilon 4 (APOE \u03b54) gene, a known genetic risk factor for the disease.<\/p>\n
\u201cThe virus and the gene may be working in tandem \u2014 a synergy where a latent viral infection \u2018flips the switch\u2019 on a genetic vulnerability,\u201d Lakhan said.<\/p>\n
Supporting a potential causal role, Itzhaki\u2019s team has since demonstrated that HSV-1 infection of cultured human neuronal cells induces the accumulation of amyloid-beta and phosphorylated tau \u2014 the primary components of amyloid plaques and neurofibrillary tangles in AD. The treatment with antiviral agents significantly reduced both these pathological markers and cell death.<\/p>\n
Are All Herpes Viruses Tied to Dementia?<\/p>\n
While research strongly suggests a link between certain herpes viruses and an increased risk for dementia, not all herpes viruses have been implicated.<\/p>\n
HSV-1 and VZV have been more consistently linked to an increased risk for dementia, including AD. While some studies suggest a possible association with HSV-2 (genital herpes), the evidence is less conclusive than that for HSV-1 and VZV.<\/p>\n
Other herpes viruses, like cytomegalovirus, have not shown a strong or consistent association with an increased dementia risk in most studies.<\/p>\n
Research has also suggested that individuals with both HSV-1 and VZV infections may face an elevated, compounded risk. In one study, patients co-infected with HSV and VZV had a hazard ratio of 1.57 for developing dementia, whereas those with HSV-1 alone had a hazard ratio of 1.38 and those with VZV alone had a hazard ratio of 1.41.<\/p>\n
Itzhaki explained that multiple biologically plausible mechanisms \u2014 supported by various studies \u2014 may explain the link between herpes virus infections and an increased risk for dementia.<\/p>\n
For instance, herpes viruses can trigger chronic inflammation in the brain, a critical factor in neurodegeneration. Additionally, HSV-1 may promote amyloid plaque formation and influence tau phosphorylation, as previously noted.<\/p>\n
The damage and risk occur as a result of reactivation of dormant HSV-1 in the brain after various types of damage, Itzhaki noted.<\/p>\n
One recent study showed reactivation of dormant HSV-1 after mild brain injury or after cumulative general infections may drive neurodegenerative diseases by triggering pathological changes including accumulation of beta-amyloid and phosphorylated tau.<\/p>\n
\u201cThe notion that a virus many of us carry could be stoking neurodegeneration is provocative, but the science behind it is becoming increasingly difficult to ignore. The past few years have delivered especially compelling data to support this viral link,\u201d said Lakhan.<\/p>\n
Antivirals, Vaccines Preventive?<\/p>\n
Some studies suggest antiviral medications used to treat herpes infections and vaccination against VZV could potentially reduce the dementia risk.<\/p>\n
For example, one recent Taiwanese cohort study<\/a> showed that symptomatic HSV-1 infection was associated with nearly a threefold increased risk of developing dementia. Antiherpetic medication reduced the risk by 90%.<\/p>\n However, a study<\/a> of US veterans showed no link between HSV infection and increased dementia risk. Nonetheless, similar to the Taiwanese study, antiherpetic medication was associated with a protective effect against dementia.<\/p>\n Separately, in a matched case-control study of nearly 700,000 older adults, HSV-1 was more common in those with AD, and antiviral therapy for HSV-1 was associated with a lower risk of developing AD.<\/p>\n