Shingles vaccination reduces the risk of Parkinson's disease

The most prevalent age-related movement condition, Parkinson's disease (PD), is characterized by bradykinesia, resting tremor, unbalanced gait, muscular rigidity, postural instability, as well as some nonmotor symptoms like autonomic and cognitive dysfunctions.

PD is caused by a loss of nerve cells in a part of the brain, the substantia nigra. These cells are responsible for producing dopamine, which acts as a messenger between the brain and nervous system that helps control and coordinate body movements. If the nerve cells in the substantia nigra die or become damaged, the amount of dopamine in the brain is reduced. Motor control is impaired, causing movements to become slow and abnormal. The loss of nerve cells is a slow process. The symptoms of PD usually only start to develop when around 80% of the nerve cells in the substantia nigra have been lost.¹

Lewy bodies and Lewy neurites collect alpha-synuclein in PD. Select peripheral autonomic nervous system neurons and central nervous system neurons are affected. The incidence of PD rises with age, and the lifetime frequency is 1%–5%. Multiple twin studies support the idea that environmental factors play a larger role in disease pathogenesis than do genetic factors, even though evidence for a few rare genetic mutations in a small subset of young people with PD cases offers some insights into the pathogenesis.²

Although the precise cause of PD is uncertain, mounting evidence points to viral infection as a potential factor. For instance, the varicella-zoster virus (VZV) may remain dormant in the ganglia and reawaken because of weakened immunity or aging. Herpes zoster (shingles) is a VZV infection that causes a painful skin rash and blisters on the dermatome infected. Herpes zoster may be related to PD, according to recent research.^{3, 4}

Herpes zoster vaccination protects against Alzheimer's disease (AD), which is related to herpes virus infection.^5-9 In the current analysis we attempted to determine if herpes zoster vaccination might reduce the risk of PD.

Data on PD prevalence by US state is from Mantri et al.¹⁰ They identified 27,538,023 Medicare beneficiaries that met inclusion criteria, of whom 392,214 had a PD diagnosis in 2014.

Data on Shingles vaccination among adults aged 60 and over in the US in 2018 is from Terlizzi and Black.¹¹ The National Health Interview Survey (NHIS) data from 2008 to 2018 were used for this investigation. The NHIS is a household survey of the civilian, noninstitutionalized US population that is conducted nationally. It is continually carried out by the National Center for Health Statistics (NCHS) during the entire year. Although follow-ups to completed interviews may be made over the phone, interviews are conducted in respondents’ homes.

Statistical analysis was performed with SPSS software (version 26.0, IBM).

District of Columbia, New York, Illinois, Connecticut, and Florida had the lowest age-adjusted prevalence ranks and highest age-adjusted prevalence of PD.

Figure 1 shows age-adjusted PD prevalence ranks in 50 US states and the District of Columbia versus the proportion of adults who had ever received a shingles vaccine. The relationship is statistically significant (p = 0.005, two-tailed). States with the most PD (lowest age-adjusted prevalence ranks) had the lowest proportion of adults aged 60 and over who had ever received a shingles vaccine. States with the highest prevalence of PD are defined to be states with the lowest prevalence ranks of PD.

The proportion of female subjects versus the proportion of adults who had ever received a shingles vaccine is in Figure 2. The relationship is statistically significant (p < 0.001, two-tailed). Increased vaccination proportion led to significantly reduced female PD prevalence. Men have a higher incidence of PD.¹²

The proportion of dual eligibility for Medicare and Medicaid versus the proportion of adults who had ever received a shingles vaccine is in Figure 3. The relationship is statistically significant (p = 0.003, two-tailed). An increased proportion of dual eligibility is associated with a diminished proportion of adults who had ever received a shingles vaccine.

Studies of Herpes zoster virus (HZV) infection and PD have been unclear as to whether HZV and PD are related. Peripheral T lymphocytes and B lymphocytes may decline over the course of PD. Herpes zoster may have the potential to develop later throughout the normal course of PD because of the reduction in cell-mediated immunity according to a theory put forth by Lai et al.⁴

In contrast, Cheng et al.² report that people with herpes zoster have a higher chance of developing PD and hypothesize that risk may be influenced by the inflammation associated with the herpes zoster infection. To pinpoint the precise pathophysiological relationship between herpes zoster and the risk of PD, more research is necessary.

PD may be due to late-life reactivation of embryologic pathways and processes silenced at birth. Viruses such as HZV may play a part.⁸

The ecological fallacy, also known as the ecological inference fallacy, is a logical fallacy in the interpretation of statistical data where inferences about the nature of individuals are derived from inference for the group to which those individuals belong.¹³ The fallacy could confound our study's results. In this instance, rather than from the individuals themselves, assumptions regarding PD in individuals are being made based on the features of the US states in which they reside.

Medicaid covers shingles vaccine only in states with expanded Medicaid coverage, not all states. Medicare covers shingles vaccination only for people with part D prescription plans. Therefore, many people with dual coverage would not be eligible for vaccine coverage. An increased proportion of Medicare Medicaid dual eligibility associated with a diminished proportion of adults who had ever received a shingles vaccine (Figure 3) implies that shingles vaccination is not being administered to many dual eligibles.

The zoster vaccine, live, was discontinued in the United States on November 18, 2020. Zoster vaccine recombinant, adjuvanted, which is more effective, is given as two intramuscular doses 6 months apart.

Cigarette smoking and coffee drinking reduce the risk of PD. Shingles vaccination could be another factor that reduces PD risk. Further studies are warranted.¹⁴

Steven Lehrer and Peter H. Rheinstein contributed equally to the conception, writing, and data analysis of this study.

The authors declare no conflict of interest.

None.