Shingles Vaccine Linked to Reduced Dementia Risk and Progression

Dr Brad Stanfield

Serendipitous Moments in Medicine [0:00]

• Medical breakthroughs often come from unexpected areas of research.
  • Examples include GLP-1 therapies for type 2 diabetes also providing relief for knee osteoarthritis.

    

  • Penicillin's accidental discovery had enormous impacts on deadly diseases.

    

• A similar serendipitous breakthrough appears to have occurred for dementia.

  

  • Recent research found a surprising protective effect from a vaccine seemingly unrelated to dementia.

    

The Varicella Zoster Virus and Dementia [1:35]

• Scientists are increasingly recognizing viruses as potential contributors to dementia.
  • Experiments in mice showed viruses stimulate a protein in the brain to fight infection.
    • This same protein clumps to form amyloid plaques, a key feature of Alzheimer's disease, suggesting the brain's defenses can backfire and accelerate dementia.

      

• The varicella zoster virus (VZV) is a chief suspect.
  • VZV causes chickenpox in childhood and can reemerge later in life as painful shingles.
  • Even asymptomatic reawakenings of VZV can act as a chronic stressor to the immune system.
    • This drives brain inflammation and interferes with immune functioning, contributing to dementia.

      

  • VZV is linked to both Alzheimer's-type brain changes (amyloid plaques) and damage associated with vascular dementia (problems in brain blood vessels like high blood pressure, plaque buildup, and strokes).

The Shingles Vaccine and Dementia [2:34]

• The question arose: could preventing VZV flare-ups (shingles) also prevent or slow dementia?
• Observational studies initially suggested a positive answer.
  • One study analyzing health records from two large US databases found a 31-35% risk reduction in dementia for those who received the shingles vaccine over an 8-year follow-up.

    

  • However, observational studies can suffer from confounding factors (e.g., healthier individuals being more likely to get vaccinated), making it difficult to establish causality.

    

  • Randomized controlled trials are the gold standard for causality, but an ethical dilemma prevents direct trials for the shingles vaccine against dementia, as it's already a recommended treatment for shingles due to proven benefits.

    

    

The Wales Dementia Study [4:13]

• Researchers in Wales identified a unique "natural experiment" due to a policy decision in 2013 regarding shingles vaccine eligibility.

  

  • The Welsh healthcare system made the shingles vaccine available to those born on or after September 2, 1933, but not those born before this date.

    

  • This created two groups of individuals, essentially the same age (around 80 in 2013), with one group eligible for the vaccine and the other not, closely resembling a randomized controlled trial.
• The study aimed to compare dementia rates between these two groups.

  

  • For those born before the cutoff, the vaccine uptake was 0.1%.
  • For those born after the cutoff (eligible), vaccine uptake was over 47%.
• Impact on Dementia Incidence:
  • Comparing the groups as a whole, those eligible for the vaccine had a 1.3% lower absolute risk and an 8.5% lower relative risk of a new dementia diagnosis over a 7-year follow-up.

    

  • Using statistical techniques to account for the fact that only about half the eligible group was vaccinated, researchers estimated that for those who actually received the vaccine, there was a 3.5% lower absolute risk reduction and a nearly 20% relative risk reduction in dementia diagnoses.
  • This 3.5% absolute risk reduction is a major finding in clinical research, translating to thousands of prevented dementia cases at a population level.
  • The benefit is also likely to grow over time beyond the 7-year follow-up.

The Impact of the Shingles Vaccine [6:33]

• The protective effects extended beyond just preventing new dementia diagnoses.
  • The vaccine also appeared to reduce new diagnoses of mild cognitive impairment (MCI), an earlier transitional stage to dementia.
  • For individuals already diagnosed with dementia before the vaccine program, receiving the vaccine was associated with a nearly 30 percentage point reduction in the death rate due to dementia over a 9-year follow-up.

    

    • While confidence intervals were wide, indicating lower certainty about the exact magnitude, the point estimates suggest a significant effect.
  • The findings primarily pertain to individuals aged 79-80 at baseline, and further research is needed for younger age groups.

    

• The shingles vaccine is a readily available, safe, and effective intervention with benefits that vastly outweigh the risks.

Addressing Potential Objections [7:09]

• The researchers addressed potential confounding factors to strengthen their findings:
  • They checked if the eligible group was generally more engaged in preventative care, finding no significant difference in other preventive behaviors.
  • They confirmed that no other significant health intervention used the same arbitrary birthdate cutoff.

    

  • Unlike some observational studies, the two groups did not differ in other common health problems, suggesting the observed divergence was specific to dementia rates.

The New Shingles Vaccine [9:33]

• The original vaccine used in the Wales study was a live-attenuated virus vaccine (Zostavax), which is being replaced by a newer recombinant vaccine (Shingrix).

  

• A concern was whether the newer vaccine would be as effective, as some evidence suggests broader health benefits are stronger with live-attenuated vaccines.
• A study in the US investigated this during a rapid shift from the old to the new vaccine after 2017.
  • The results were reassuring: the newer recombinant vaccine was associated with an even lower risk of dementia.

    

  • This suggests the new vaccine maintains or improves the protective effect against dementia.

Other Potential Strategies to Reduce Dementia Risk [10:24]

• Beyond vaccination, other recent developments offer strategies to reduce dementia risk:
  • Lithium Orotate: Exciting evidence suggests this specific form of lithium could slow Alzheimer's development.
    • A mouse study showed it blocked key hallmarks of disease progression.

      

  • Addressing Hearing Loss: This intervention also yields significant benefits.
    • A systematic review found that people with hearing loss who used hearing aids had a significantly lower risk of cognitive decline and dementia compared to those who did not.

      

Supplements That May Lower Dementia Risk [11:02]

• Research suggests certain supplements may protect the brain and lower dementia risk:
  1. Multivitamin and Mineral Supplement:
     • A large trial over two years showed relative improvements in overall cognition scores and memory.
     • The effect on cognition was equivalent to reducing the speed of brain aging by two years.

       

  2. Omega-3 Fatty Acids:
     • Naturally found in fatty fish, these are critical for brain health.
     • A 2019 study found omega-3 supplements improved brain performance by 7.1% and reduced dementia symptoms by 22.3%.

       

     • Adequate B vitamins were crucial for these benefits, further supporting multivitamin use.
  3. Creatine:
     • Known for boosting exercise performance, creatine is also abundant in the brain and vital for energy production.

       

     • Research suggests creatine supplements can increase brain creatine levels, supporting memory and thinking.
     • A 2022 meta-analysis showed improved memory performance, particularly in older adults.

       

  4. TMG (Trimethylglycine):
     • TMG is linked to Alzheimer's disease through homocysteine levels.
     • High levels of homocysteine (an amino acid) are strongly linked to Alzheimer's disease.
     • TMG lowers homocysteine, suggesting it may lower a key risk factor for Alzheimer's.

       

Conclusions & Key Takeaways [13:12]

• The findings regarding the shingles vaccine offer a promising, simple, and cheap intervention to prevent and treat dementia.
• While more research is ongoing, the evidence is compelling.