A large population-based study conducted in South Korea found that three allergic diseases were associated with an increased risk of developing dementia, but independent experts who reviewed the data did not find statistically significant Although statistically significant, the effect size may be small.
Asthma, allergic rhinitis, and atopic dermatitis (a common allergic disease sometimes called “atopic triad”) are significantly associated with an increased risk of dementia, according to a new prospective study by Korean researchers. increase.
The study is one of the largest studies to date on the link between allergic disease and dementia. But until further studies replicate the studies in other groups and shed light on the mechanisms underlying the association, the implications for clinical practice will remain unknown, experts said. Neurology Today.
A growing body of evidence points to links between dementia etiology and chronic neuroinflammation and immune dysregulation in the brain. Observational studies have linked inflammatory conditions such as rheumatoid arthritis, chronic periodontitis, psoriasis, obesity, and type 2 diabetes to increased risk of dementia, suggesting that chronic peripheral inflammation may play a role in the pathophysiology of dementia. suggests that there is a
However, so far, only a few prospective studies have examined the association between allergic diseases and dementia. The results of these studies have been somewhat inconsistent, but most have found at least some association between one or more of these diseases and the risk of dementia.
The current study was published online on September 23. Chronicles of Neurology, Investigators tapped into the vast data power of South Korea’s National Health Insurance system. The system is compulsory for all South Korean citizens and provides free national health examinations for the entire population over the age of 40 and workplace subscribers of all ages. Their final analysis included his total study population of 6,785,948 who entered the system in 2009, but who had missing variables in their records and who had a history of dementia before baseline. were excluded.
To identify individuals with allergic diseases, researchers used the ICD-10 codes for asthma, allergic rhinitis, and atopic dermatitis. To rule out episodic illnesses that mimic allergic diseases, they defined allergic patients as those who had at least three annual outpatient visits for each allergic disease.
They prospectively followed participants for diagnosis of dementia onset from 2009 to 2017. Primary endpoints were newly diagnosed all-cause dementia, Alzheimer’s disease (AD), and vascular dementia. During follow-up, they identified 260,705 cases of dementia in him (including 195,739 AD and 32,789 vascular dementia).
The researchers found that each allergic disease was associated with an increased risk of dementia even after adjusting for confounding variables such as gender, age, and other known risk factors such as BMI, smoking, alcohol use, physical activity, and comorbidities. For example, asthma was positively associated with the risk of all-cause dementia (HR=1.20), AD (HR=1.22), and vascular dementia (HR=1.09). bottom. Allergic rhinitis was associated with an increased risk of all-cause dementia (HR=1.10) and AD (HR=1.13), but not vascular dementia (HR=1.01). Atopic dermatitis was also associated with increased risk of all-cause dementia (HR=1.16), AD (HR=1.15), and vascular dementia (HR=1.18).
The study also found a ‘dose-response’ association between allergic disease and dementia risk. Those with more visits had a significantly higher risk of all-cause dementia, Alzheimer’s disease, and vascular dementia, with the exception of allergic rhinitis, which is associated with VaD risk (although outpatient visits were more subdivided). , the frequency of annual visits for allergy patients is 10 or more). Rhinitis was also associated with an increased risk of vascular dementia (HR=1.07)). He of the allergic triad also had a significant risk of all-cause dementia (HR = 1.54), AD (HR = 1.46), and vascular dementia (HR = 1.95) in those with all three conditions. was increasing.
Independent Expert Perspective
“This study makes an important contribution to our understanding of the relationship between allergic diseases and dementia in middle-aged and older age groups,” said Zoe Arvanitakis, professor of neuroscience at Rush University and Rush School of Medicine. , MD, MS, FAAN said. Director of the Rush Memory Clinic at the Rush Alzheimer’s Center.
“Prior to this study, the data on this relationship were much less convincing due to the small sample size and unreliable study design,” said Dr. Arvanitakis, who was not involved in the study. increase.
“The fact that these researchers had such a large sample size allowed them not only to study three important allergic diseases, including asthma, which is becoming more common, but [also] We aim to categorize the risks associated with each of these three diseases and segregate the outcomes of Alzheimer’s disease and vascular dementia separately. “
“The sample size also allowed us to do a stratified analysis to account for potentially important co-founder influences such as age,” she continued. We use a very comprehensive approach in our analysis, which gives us even more confidence in the validity of our results.”
Dr. Keenan Walker is Director of Multimodal Imaging in the Neurodegenerative Diseases Unit within the Institute of Behavioral Neuroscience at the National Institute on Aging, whose research has focused on abnormal immune function and inflammation in Alzheimer’s disease and cognitive decline in older age. Focused. Significant research on this topic to date”.
“Given what we’ve seen in other epidemiological studies linking autoimmune and general inflammatory conditions with dementia risk, this is something many people have wondered,” he said. “I study inflammation and am often asked if allergies increase the risk of dementia, but the lack of solid evidence has prevented me from giving a good answer. Allergies and Allergic Conditions” is likely to be a weak risk factor, a larger population is needed to assess association, which is one of the key strengths of this study, and the findings are highly consistent across subgroups. It seems consistent.”
Another strength of this study is the ability to classify Alzheimer’s dementia and vascular dementia into different subgroups.
“While the causes of these two forms of dementia have many similarities, they are also different in many ways, and this study suggests, for example, that some of the allergic conditions are more associated with AD than with vascular dementia. This suggests that allergic conditions may interact with some of the molecular factors unique to Alzheimer’s disease, such as amyloid beta and tau. ”
Of course, there are limits.
“One important factor is that the study was conducted in South Korea. Therefore, whether these results apply to other populations in the world, as well as to U.S. populations with different genetic makeup and different environmental exposures. Dr. Arvanitakis said, “It’s not a large study that could easily be done in the United States because of the different healthcare systems. For example, we used the Medicare billing system. There are large population-based studies, such as studies, that include people aged 65 and over.”
One of the strengths of the Korean study was that participants were young (in their 40s) at baseline.
“[W]Because many of these risk factors carry burdens over many years and are often not the effects of a single event or exposure, it is important to understand the role of risk factors in middle and later life. I know that it is
What is behind the association?
Tharik Pascoal, M.D., Ph.D., assistant professor of psychiatry and neurology at the University of Pittsburgh, said the study raises even more questions. “These are phenomenological discoveries, after all,” he said. “What is the mechanism behind this association?”
He proposed three possible explanations for the link between allergic disease and dementia.
“First, peripheral inflammation associated with conditions such as asthma and allergies activates microglia, increasing inflammation in the brain and potentially leading to dementia.
A second possible etiology is drug effects. “Some studies suggest that drugs associated with these allergic diseases, such as anticholinergics, may also be involved in dementia,” he said. “And interestingly, second-generation drugs, which are less likely to cross the blood-brain barrier, appeared to have a lower risk of dementia than first-generation drugs.”
Finally, Dr. Pascoal speculated that allergic diseases and dementia may have a common underlying medical condition, rather than one disease causing another.
“Isn’t an allergy at the end of the day an overreaction of the immune system to something innocuous?” he asked. “Both of these conditions may be the result of an overactive immune system, as it has also been hypothesized that dysregulation of the immune system in the brain plays a key role in Alzheimer’s disease.”
Each of these possible mechanistic explanations has different implications for prevention and management, he said.
“If allergic disease-induced inflammation activates inflammation in the brain, this may be a modifiable risk factor, leading to more aggressive treatment of allergic disease to reduce the risk of dementia in the future.” We may need to,” Dr. Pascoal noted. “But if the association is the result of medication, more aggressive treatment may increase the risk of dementia. This is a very good paper that suggests the right questions to ask next, but more mechanistic studies, including animal model studies, are needed.”
Dr. Arvanitakis says other studies have also looked at how inflammation may indirectly affect the brain.
“For many years, there has been interesting research into chronic dental conditions, such as gum inflammation, and how it may be associated with dementia, which is why inflammation Is it because of the process itself, or because other studies have suggested that chronic infections like HIV may be linked to dementia,” she said. “Recently, we know that other infectious etiologies, such as the virus that causes COVID, can have indirect inflammatory effects on the brain.”
Meanwhile, Dr. Walker cautioned against warning patients about the association.
“This study is great in terms of generating hypotheses and suggesting more avenues of research, but it’s very early in terms of connecting the dots,” he said. We do not want these findings to scare about 20% of the population because they are prevalent. It should be noted that there is an increase of about %, which is a significant finding because these diseases are so prevalent, but at the individual level the increase in risk is very small.”