Shingles vaccines and statins have been found, separately, to significantly reduce the risk of dementia, which researchers say is of "tremendous importance" in the fight against the disease.
MedicalBrief reports that the encouraging results come on the heels of improved tests – developed by local researchers with international partners – that could precisely detect cognitive dysfunction in ageing African adults (see story in Research Highlights below).
In sub-Saharan Africa, a dramatic rise in dementia prevalence is projected by 2050 because of an increasing ageing population. In South Africa, in particular, more than 1m people could be affected by dementia in the upcoming decades, solidifying what is known about the significant community, social, and economic impact of dementia in rural areas.
Meanwhile, the findings by a team of South Korean scientists suggest that taking statins could reduce the risk of dementia among people who already have low cholesterol, while 10 000km away, older adults in Wales who’d had a shingles jab were found 20% less likely to be diagnosed with dementia that those had not been vaccinated, confirming previous studies.
In the latter study, the researchers who had tracked dementia cases in Welsh adults said they had uncovered the strongest evidence yet that the shingles vaccination reduces the risk of developing the devastating brain disease.
Health records of more than 280 000 older adults revealed that those who received a largely discontinued shingles vaccine called Zostavax were 20% less likely to be diagnosed with dementia over the next seven years than those who went without.
Pascal Geldsetzer, at Stanford University, told The Guardian: “For the first time we are able to say much more confidently that the shingles vaccine causes a reduction in dementia risk. If this truly is a causal effect, we have a finding that’s of tremendous importance.”
The researchers took advantage of a vaccination roll-out that took place in Wales more than a decade ago. Public health policy dictated that from 1 September 2013, people born on or after 2 September 1933 became eligible for the Zostavax shot, while those who were older missed out.
The policy created a natural experiment where the older population was sharply divided into two groups depending on their access to the vaccine. This allowed the researchers to compare dementia rates in older people born weeks apart but on either side of the vaccine eligibility divide.
After accounting for the fact that not all those eligible for the vaccine received it, the researchers found vaccination led to a 20% reduction in dementia risk, with the strongest effect in women.
Anupam Jena, a professor of healthcare policy at Harvard Medical School, said the implications were profound.
Dementia affects more than 55m people globally and is the leading cause of death in the United Kingdom. One in three will develop the condition in their lifetime, and while drugs that slow the disease have recently been approved, there is no cure.
When people contract chickenpox the virus remains dormant in their nerve cells for life. But the virus can reactivate and cause shingles in older people whose immune systems are waning, or in individuals with weakened immunity.
The latest work, published in Nature, is not the first hint that shingles vaccines might shield against dementia.
When Zostavax was rolled out in the United States in 2006, several studies found lower rates of dementia in people who received the shots. Last year, Oxford researchers reported an even stronger protective effect in people who received Shingrix, a newer vaccine.
Geldsetzer is now looking for philanthropic and private foundations to fund a randomised clinical trial to confirm any benefits.
It is unclear how shingles vaccines might protect against dementia, but one theory is that they reduce inflammation in the nervous system by preventing reactivation of the virus. Another theory is that the vaccines induce broader changes in the immune system that are protective. These wider effects are seen more often in women, potentially explaining the sex differences in the study.
In an accompanying article, Jena wrote: “Although it is still unclear precisely how herpes zoster vaccination lowers the risk of dementia, the implications of the study are profound. The vaccine could represent a cost-effective intervention that has public-health benefits strongly exceeding its intended purpose.”
Maxime Taquet, whose Oxford study found a reduced dementia risk after Shingrix vaccination, said adjuvants in that vaccine, which make the immune response more potent, may play a role.
Both studies “provide strong support for the hypothesis that shingles vaccination reduces dementia risk, with the newer recombinant vaccine offering superior protection”, he said. “A key question is whether this enhanced protection is due to improved shingles prevention or the adjuvant’s immunological effects.”
Statins
And in the argument for statins, the research, published in the BMJ’s Journal of Neurology, Neurosurgery and Psychiatry, found that people taking statins with healthy levels of “bad” cholesterol in their blood were at reduced risk of the neurological condition compared with those with high levels.
But they also found the dementia risk reduced further among those who already had low cholesterol and were taking statins compared to those who were not, suggesting the drugs provide “additional protective effects”.
While statins are usually prescribed to people in their 60s or 70s, the findings raise the prospect they could be given to younger people with normal levels of cholesterol as a way of protecting the health of both their heart and brain.
The researchers said the drugs were providing a “synergistic effect” and could have a much bigger role to play in brain and cognitive health than previously thought, reports The Telegraph.
Statins are one of the most commonly prescribed drugs in the UK, with around 7m to 8m people taking the cheap, daily pills to cut their chance of heart attack and stroke.
‘More to Alzheimer’s than we first thought’
The medicine can help lower the level of low-density lipoprotein (LDL) cholesterol in the blood, often referred to as the “bad cholesterol” because it can lead to plaque build-up in arteries and increase the chance of strokes, heart attacks and heart disease.
Researchers from South Korea, led by Hallym University and Kangdong Sacred Heart Hospital in Seoul, said their findings “underscore the crucial role of managing LDL- C in lowering dementia risk”.
They examined health data on more than 570 000 people aged 18 and older in South Korea.
The NHS says that people should aim for bad cholesterol levels in the blood to be below 4mmol/L (millimoles per litre).
The study teams found that people with low LDL cholesterol levels below 1.8 mmol/L were 26% less likely to develop dementia and 28% less likely to develop Alzheimer’s, compared with those with levels above 3.4 mmol/L – the higher end of a healthy range.
Taking statins saw those with LDL cholesterol levels below 1.8 mmol/L reduce their dementia risk by a further 13% and 12% for Alzheimer’s compared with people who do not take them.
“These findings emphasise the importance of targeted LDL- C management as part of dementia prevention strategies, with potential integration into clinical guidelines,” the authors wrote in the Journal of Neurology Neurosurgery and Psychiatry.
“The results support the use of statin therapy within specific LDL- C ranges for both cardiovascular and cognitive health benefits.”
The study found the benefits of statins tailed off among people whose LDL cholesterol levels were “very low” and had fallen below 0.8 mmol/L, suggesting a threshold with “optimal benefit” that should be targeted and personalised to individuals.
“This insightful understanding of how statin use interacts with LDL- C levels emphasises the need for personalised statin prescriptions, focusing on achieving LDL- C levels that offer the maximum cognitive benefits.”
Dr Francesco Tamagnini, neurophysiologist at the University of Reading, said there was “clearly more to the story of Alzheimer’s than we first thought”.
“The results give a convincing argument for researchers to consider LDL cholesterol in addition to the classic approaches,” he said, hypothesising “that damage to the blood-brain barrier can lead to accumulation of LDL cholesterol in the brain and potentially alter the electrical activity of neurons.”
He said proteins, amyloid and tau, had been widely considered as the “main cause of Alzheimer’s but that is an opinion that is now likely to fade”.
“Alzheimer’s disease may be a complication caused by the accumulation of LDL in the brain. What we now need to find out is exactly how the high levels of lipids in the blood are causing Alzheimer’s and other types of dementia.”
Opening new avenues
Dr Julia Dudley, the head of research at Alzheimer’s Research UK, said both studies were encouraging.
She said the shingles study strengthened the emerging link between vaccination and reduced dementia risk, and that while previous studies suggested an association, “this offers stronger evidence of a direct link, with greater benefit observed in women”.
“It’s unclear exactly how the shingles vaccine might influence dementia risk. It may reduce inflammation, support the immune system in ways that protect the brain or involve other mechanisms. It’s important to note that this study looked at the Zostavax vaccine rather than Shingrix, which is now more commonly used.
“Understanding this link better, including the reason for any differences between men and women, could open new avenues for dementia prevention and treatment,” she said.
And on the statins findings, she said these suggested that statins “seem to offer a protective effect – even in those who already had cholesterol levels within a lower range”.
“However, dementia risk is complex and influenced by many factors. Without a detailed picture of what’s going on in the brain we do not know if there is a direct link between lower cholesterol and reduced dementia risk.”
She said trials would be key to understand what effects statins might be having on disease processes in the brain.
Study 1 details
A natural experiment on the effect of herpes zoster vaccination on dementia
Markus Eyting, Min Xie, Pascal Geldsetze et al.
Published in Nature on 2 April 2025
Abstract
Neurotropic herpesviruses may be implicated in the development of dementia. Moreover, vaccines may have important off-target immunological effects. Here we aim to determine the effect of live-attenuated herpes zoster vaccination on the occurrence of dementia diagnoses. To provide causal as opposed to correlational evidence, we take advantage of the fact that, in Wales, eligibility for the zoster vaccine was determined on the basis of an individual’s exact date of birth. Those born before 2 September 1933 were ineligible and remained ineligible for life, whereas those born on or after 2 September 1933 were eligible for at least one year to receive the vaccine. Using large-scale electronic health record data, we first show that the percentage of adults who received the vaccine increased from 0.01% among patients who were merely one week too old to be eligible, to 47.2% among those who were just one week younger. Apart from this large difference in the probability of ever receiving the zoster vaccine, individuals born just one week before 2 September 1933 are unlikely to differ systematically from those born one week later. Using these comparison groups in a regression discontinuity design, we show that receiving the zoster vaccine reduced the probability of a new dementia diagnosis over a follow-up period of seven years by 3.5 percentage points (95% confidence interval (CI) = 0.6–7.1, P = 0.019), corresponding to a 20.0% (95% CI = 6.5–33.4) relative reduction. This protective effect was stronger among women than men. We successfully confirm our findings in a different population (England and Wales’s combined population), with a different type of data (death certificates) and using an outcome (deaths with dementia as primary cause) that is closely related to dementia, but less reliant on a timely diagnosis of dementia by the healthcare system. Through the use of a unique natural experiment, this study provides evidence of a dementia-preventing or dementia-delaying effect from zoster vaccination that is less vulnerable to confounding and bias than the existing associational evidence.
Study 2 details
Low-density lipoprotein cholesterol levels and risk of incident dementia: a distributed network analysis using common data models
Minwoo Lee, Kyung Joo Lee, Jinseob Kim et al.
Published in The BMJ Journal of Neurology, Neurosurgery and Psychiatry on 21 March 2025
Abstract
Background
The link between low-density lipoprotein cholesterol (LDL-C) levels and dementia risk is poorly understood, with conflicting evidence on the role of LDL-C and the impact of statin therapy on cognitive outcomes. Thus, we aimed to examine the association between low-density LDL-C levels and the risk of dementia and assess the influence of statin therapy.
Methods
We retrospectively analysed data from 11 university hospitals participating in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). Participants with a prior diagnosis of dementia or those with <180 days of observation before cohort inclusion, and those included in both cohorts were excluded. The primary outcome was all-cause dementia, with the secondary outcome being Alzheimer’s disease-related dementia (ADRD). The study utilised 1:1 propensity score matching to compare individuals with LDL-C levels below 70 mg/dL (1.8 mmol/L) against those with levels above 130 mg/dL (3.4 mmol/L), resulting in a primary analysis cohort of 108 980 matched patients. Secondary analyses further examined LDL-C thresholds below 55 mg/dL (1.4 mmol/L) and the influence of statin use.
Results
The LDL-C levels below 70 mg/dL (1.8 mmol/L) were associated with a 26% reduction in the risk of all-cause dementia and a 28% reduction in the risk of ADRD, compared with levels above 130 mg/dL (3.4 mmol/L). For LDL-C levels below 55 mg/dL (1.4 mmol/L), there was an 18% risk reduction for both outcomes. Among those with LDL-C <70 mg/dL (<1.8 mmol/L), statin use was associated with a 13% reduction in all-cause dementia risk and a 12% decrease in ADRD risk compared with non-users.
Conclusion
Low LDL-C levels (<70 mg/dL (<1.8 mmol/L)) are significantly associated with a reduced risk of dementia, including ADRD, with statin therapy providing additional protective effects. These findings support the necessity of targeted lipid management as a preventive strategy against dementia, indicating the importance of personalised treatment approaches.
Nature linked article – Could the shingles vaccine help to prevent dementia? (Open access)
See more from MedicalBrief archives:
Shingles jab may help ward off dementia – UK study
How close are scientists to developing a dementia vaccine?
Statins may reduce Alzheimer’s disease risk by up to 15%