An episode of shingles—a painful, bubbling rash that erupts in patients who’ve had chickenpox—is associated with a significantly higher long-term risk of subjective cognitive decline (SCD), a new study published in Alzheimer’s Research & Therapy has found.

Yeh T-S, Curhan GC, Yawn B, et al. Herpes zoster and long-term risk of subjective cognitive decline. Alzheimer’s Research & Therapy. 2024;16(1).

The shingles, or herpes zoster virus, lies dormant in the body in people who’ve had chickenpox (the varicella-zoster virus, or human herpesvirus 3), David Cutler, MD, a board-certified family medicine physician at Providence Saint John’s Health Center in Santa Monica, CA, tells MDLinx.

Shingles: Who gets and causes. American Academy of Dermatology Association.

“[Shingles] lives in the nerve ganglia, and [when activated] climbs up along the nerves, causing pain and a rash,” Dr. Cutler says. A suppressed immune system or a coexisting infection could trigger a reactivation of the virus, which shows up as shingles and not chickenpox. Age could also play a role. However, Dr. Cutler notes, triggers for shingles aren’t entirely understood. 

When improperly treated or left untreated, the fiery, tingling nerve pain can persist for months or even years, Dr. Cutler says. It can lead to long-term nerve pain called postherpetic neuralgia in the area where the rash was located.

Centers for Disease Control and Prevention. Shingles Symptoms and Complications. April 19, 2024.

Another long-term complication? Researchers now think shingles are associated with SCD, the self-reported experience of worsening or more frequent confusion, memory loss, and inability to learn or make judgments, according to the Centers for Disease Control and Prevention (CDC). 

SCD occurs early on in patients with Alzheimer’s disease and other dementias, and it can play a major role in reducing a patient’s autonomy and quality of life. It isn’t a diagnosis, as it refers to one’s subjective experience, but it can indicate greater cognitive concerns.  In the United States, cognitive decline is a public health problem, with around 11% of people over age 45 experiencing SCD.

Why Subjective Cognitive Decline is a Growing Health Issue Among Women.

It tends to occur more often in those over the age of 65, although it does also occur in those between the ages of 45 and 64. SCD occurs more frequently in Black and African American populations.

Wooten KG, McGuire LC, Olivari BS, et al. Racial and Ethnic Differences in Subjective Cognitive Decline - United States, 2015–2020. MMWR Morbidity and Mortality Weekly Report. 2023;72(10):249–255.

A closer look at the study

To determine SCD in patients with and without shingles, the researchers looked at the association between shingles and SCD in 149,327 participants across three large cohorts. These included the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS). The researchers calculated risk by looking at SCD scores relative to years since shingles occurred, and compared these findings to patients without a history of shingles. 

The findings

• Across the cohorts, shingles were associated with an approximately 20% higher long-term risk of SCD.

• In the NHS cohort, patients who had shingles 13 years or longer ago saw a higher long-term risk of SCD compared to patients without shingles.

• In the NHS II cohort, shingles was associated with higher risk of SCD in both the short term (1–4 years) and long term (13 years or more) since shingles was found.

• In the HPFS cohort, SCD risk was higher no matter the timeline since a patient had shingles. In patients with data on APOE ε4—the strongest genetic risk factor for Alzheimer's disease (AD)—the researchers believe the risk for SCD may be higher in male APOE ε4 carriers vs women.

  DiBattista AD, Heinsinger NM, Rebeck GW. Alzheimer’s Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function. Current Alzheimer’s Research. 2016;13(11):1200–1207.

   

   

• There was also an association between a higher long-term risk of SCD in women without a shingles vaccination, but additional research is needed in this area.

The researchers concluded that “herpesviruses may influence the risk of cognitive decline and dementia…through neuroinflammation, cerebral vasculopathy, or direct neuronal damage.”

Yeh T-S, Curhan GC, Yawn B, et al. Herpes zoster and long-term risk of subjective cognitive decline. Alzheimer’s Research & Therapy. 2024;16(1).

The researchers also noted that findings are inconclusive regarding whether or not vaccination against shingles plays a role in preventing cognitive decline. They say that high-quality prospective cohort studies are needed to understand this relationship better.

There is no conclusive way to prevent SCD, but researchers believe that exercise, healthy diet, and vascular risk management are key. Shingles prevention could also play into risk mitigation.

Forcano L, Fauria K, Soldevila-Domenech N, et al. Prevention of cognitive decline in subjective cognitive decline APOE ε4 carriers after EGCG and a multimodal intervention (PENSA): Study design. Alzheimer’s and Dementia. 2021;7(1):e12155.