Study: Shingles Could Significantly Increase Risk of Dementia and Parkinson Disease

Clinical studies have examined the relationship between herpes zoster (HZ) and dementia or Parkinson disease (PD), although the results have been inconsistent. Some findings demonstrated an increased risk of PD in patient with herpes zoster, whereas others found opposite results.¹

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Dementia is a progressive brain disorder that impacts cognition and memory, accounting for a large number of deaths worldwide. According to the Alzheimer’s Association, approximately 7 million individuals in the US are living with Alzheimer disease (AD) and dementia, and the number is expected to reach nearly 13 million by 2050. Among the various risk factors tied to dementia, studies suggest that HZ could also play a role, but this has not yet been confirmed.²

PD is also a progressive brain disorder, but rather than impacting memory, the condition effects movement. Early symptoms of PD can be mild but worsen overtime, including tremors, slowed movement, rigid muscles, poor posture and balance, loss of automatic movements, speech and writing changes, and nonmotor symptoms.³ The study authors noted that PD has a lifetime prevalence of 1% to 5%.¹

In order to better understand the connection between dementia and PD with HZ, researchers collected, analyzed, and summarized data from various studies across the PubMed, Cochrane, Embase, and Web of Science Core Collection databases.¹

The study authors noted that meta-analyses were conducted using Review Manager 5.4.1, with Hazard Ratios (HRs) as the primary outcome measure, and 95% confidence intervals were calculated for all outcomes. Heterogeneity between studies was assessed using the inconsistency index (I²), with significant heterogeneity defined as p-value less than 0.05 or I² greater than 50%. A random-effects model was used for all analyses, and potential publication bias was evaluated using funnel plots and Egger's regression tests for studies with 10 or more included. Statistical significance was determined at the p-value below 0.05 level.¹

A total of 1077 publications were searched—359 from PubMed, 434 from Embase, 19 from Cochrane, and 265 from Web of Science Core Collection, including 13 studies in the analysis.¹

The results demonstrated a potential association between HZ and an increased risk of dementia, particularly vascular dementia, although this association did not reach statistical significance in all analyses. Additionally, a significant increase in the risk of (PD) following herpes zoster infection was observed.¹

The study authors noted that potential mechanisms contributing to these findings include varicella zoster virus (VZV)-induced vasculopathy leading to cerebral infarction and vascular dementia, neuroinflammation worsening AD pathology, α-synuclein aggregation and mitochondrial dysfunction contributing to PD development, and potential interactions with human endogenous retroviruses.¹

The subgroup analysis found that factors such as follow-up duration, sample size, and participant age did not significantly impact the observed association between HZ and dementia risk. However, a clear positive association between HZ and dementia risk was evident in prospective studies, whereas retrospective studies did not show a significant association. Notably, in a sensitivity analysis where a larger number of retrospective studies were excluded, a trend emerged suggesting an increased risk of dementia associated with herpes zoster.¹

However, prospective studies and Mendelian randomization analyses are needed to further investigate these associations and clarify the underlying causal mechanisms, while considering factors such as dementia subtype, VZV location, and other potential confounders, according to study authors.¹

To mitigate the risks, researchers recommend early vaccination against HZ because the varicella zoster vaccine (Shingrix; GlaxoSmithKline) has displayed overall efficacy of 97.2%.¹

“The findings indicate that HZ significantly raises the risk of PD and vascular dementia. Additionally, a causal relationship exists between herpes zoster infection and dementia,” the study authors said in a news release.¹

REFERENCES

1. Association between herpes zoster and Parkinson’s disease and dementia: a systematic review and meta-analysis. Frontiers in Neurology. News release. December 5, 2024. Accessed December 23, 2024. https://pmc.ncbi.nlm.nih.gov/articles/PMC11655326/.

2. Alzheimer’s disease facts and figures. Alzheimer’s Association. 2024. Accessed December 23, 2024. https://www.alz.org/alzheimers-dementia/facts-figures.

3. Parkinson's disease. Mayo Clinic. News release. September 27, 2024. Accessed December 23, 2024. https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055#:~:text=Age.,Parkinson's%20disease%20than%20are%20women.