The effect of shingles vaccination at different stages of dementia

Overview of Findings

• Multiple papers (including a Wales “natural experiment”) suggest shingles (HZ) vaccination reduces dementia risk by roughly 20% over ~7 years.
• The Cell paper refines this: vaccination reduces new diagnoses of mild cognitive impairment (MCI) by ~3 percentage points over 9 years and lowers dementia deaths among those already diagnosed.
• Effect appears across the clinical course: fewer MCI cases, fewer dementia diagnoses, and slower progression once dementia exists.

Causality and Study Design

• Key strength: quasi-random “date-of-birth” eligibility (e.g., Wales cutoff in 1933) approximates a randomized trial and reduces usual observational confounders.
• Commenters view this as unusually strong evidence in a field where amyloid-focused approaches have yielded little.
• Some still stress correlation vs causation; others argue the design plus consistency across datasets is highly persuasive.

Mechanisms and Biological Theories

• Shingles/chickenpox virus (VZV) is neurotropic and lives in nerves for decades; reactivation causes inflammation and damage.
• Hypotheses:
  • Direct: preventing VZV reactivation reduces cumulative neural injury and thus dementia.
  • Indirect: vaccine-induced immune modulation (e.g., via adjuvants) broadly reduces harmful neuroinflammation.
• Evidence so far points to reduction in all-cause dementia, not just Alzheimer’s.
• Antiviral valacyclovir failed in an early-stage Alzheimer’s trial, possibly because intervention was too late.

Vaccine Types and Comparisons

• Older vaccine Zostavax (live attenuated) vs newer Shingrix (recombinant with adjuvant).
• Earlier dementia studies centered on Zostavax, but newer work suggests Shingrix may have an equal or larger dementia-protective effect, possibly due to its adjuvant.
• Separate discussion: childhood varicella vaccine (live attenuated) appears to reduce later shingles risk substantially; its dementia impact is still unclear.

Age Limits, Access, and Risk–Benefit

• Many under-50s report getting shingles (sometimes severe) but struggle to obtain Shingrix due to regulatory age cutoffs and pharmacy policies.
• Some clinicians advise delaying vaccination (e.g., until 60) to align protection with very old age, while others and many commenters favor vaccinating as soon as eligible given shingles’ severity and the new dementia data.
• Side-effect risks (e.g., rare Guillain–Barré) and cost are acknowledged, but most commenters see HZ vaccination as strongly net-beneficial.

Broader Context and Attitudes

• Thread connects shingles to a wider pattern: latent viral infections (VZV, EBV, HSV) and chronic inflammation as drivers of neurodegeneration.
• There is tension between trust in expert consensus and skepticism fueled by past public-health missteps, but most participants converge on: get vaccinated against shingles if you can.