Medical Bulletin 30/ August/ 2024 - Video

Two new studies linked to the journal Alzheimer's & Dementia revealed that epigenetic markers in the blood could be useful for understanding dementia risk.

Researchers conducted study on the role of DNA methylation, an epigenetic marker, in exploring how genetic and lifestyle factors impact dementia risk.

DNA methylation involves adding a chemical tag to DNA to regulate gene activity, turning genes on or off. Variations in genetic and lifestyle factors can modify these DNA methylation tags, with some factors already recognized for their potential to increase dementia risk. By evaluating DNA methylation patterns, researchers can gain insights into how these factors affect dementia risk and the underlying mechanisms that contribute to the disease.

Researchers analyzed DNA methylation at 800,000 genomic sites using blood samples from 900 individuals. Instead of spinal fluid, they chose to collect blood samples due to the lower cost and greater ease of collection.

In the first of the two papers, researchers demonstrated that DNA methylation patterns in the blood can reflect the levels of certain protein biomarkers typically measured in spinal fluid for dementia assessment. They investigated these methylation patterns alongside 15 different spinal fluid biomarkers used for diagnosing dementia, revealing alterations in the methylation status of key genes associated with several of these biomarkers.

In the second study, the team developed epigenetic risk scores based on blood DNA methylation patterns to represent 14 established dementia risk factors. These factors included modifiable lifestyle risks like physical activity and diet, as well as non-modifiable factors such as age and heart disease.

Overall, researchers demonstrated that their epigenetic risk scores can enhance the prediction of cognitive decline and the onset of dementia, even at early stages. Early detection is essential for improving lifestyle management and accessing potential new treatments. The paper underscores the role of genetic, lifestyle, and environmental factors in the development and progression of dementia, emphasizing their influence through epigenetic mechanisms.

Reference: Smith, R. G., Pishva, E., Kouhsar, M., Imm, J., Dobricic, V., Johannsen, P., Wittig, M., Franke, A., et al(2024). Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study. Alzheimer's & Dementia. https://doi.org/10.1002/alz.14098

Koetsier, J., Cavill, R., Reijnders, R., Harvey, J., Homann, J., Kouhsar, M., Deckers, K., et al (2024). Blood-based multivariate methylation risk score for cognitive impairment and dementia. Alzheimer's & Dementia. https://doi.org/10.1002/alz.14061

A new study published in the journal Diabetes Care has found that type 2 diabetes and prediabetes are linked to accelerated brain ageing and also healthier lifestyle could prevent brain ageing in diabetes.

Type 2 diabetes is recognized as a risk factor for dementia, but its impact on brain ageing in individuals without dementia, including those with prediabetes, remains unclear. A recent extensive brain imaging study reveals that both diabetes and prediabetes are linked to accelerated brain ageing.

The study analyzed data from over 31,000 individuals aged 40 to 70 who had undergone brain MRI scans. Using machine learning, researchers estimated brain age relative to chronological age.

Results showed that prediabetes and diabetes were associated with brains that were, on average, 0.5 and 2.3 years older than their chronological age, respectively. In individuals with poorly managed diabetes, the brain appeared more than four years older than its chronological age.

Additionally, the disparity between brain age and chronological age tended to widen over time in those with diabetes. However, these effects were less pronounced in people who engaged in high levels of physical activity and avoided smoking and excessive alcohol consumption.

A subset of participants in the study had multiple MRI scans conducted over time. Current research includes ongoing follow-up MRI examinations to further investigate how diabetes affects brain ageing throughout different periods. This continued analysis aims to deepen the understanding of the long-term relationship between diabetes and the progression of brain ageing.

Reference: Abigail Dove, Jiao Wang, Huijie Huang, Michelle M. Dunk, Sakura Sakakibara, Marc Guitart-Masip, Goran Papenberg, Weili Xu; Diabetes, Prediabetes, and Brain Aging: The Role of Healthy Lifestyle. Diabetes Care 2024; dc240860. https://doi.org/10.2337/dc24-0860

In a recent study published in BMC Public Health, researchers assessed the impact of smoking on the prevalence of stroke. They explored the relationship between smoking-related factors and stroke risk, while also analyzing how demographic differences might affect this association.

Stroke results in significant illness and death globally and can be classified as either ischemic or hemorrhagic, arising from damage to the brain's blood vessels and tissues. The risk of stroke is associated with oxidative stress, inflammation, autophagy, and apoptosis.

Elevated smoking rates, familial smoking habits, and high levels of harmful tobacco components such as carbon monoxide, nicotine, and tar all increase the risk of stroke.

These factors reflect both the level of exposure to smoking and the frequency of smoking, as well as the potential harm inflicted by inhaled smoke.

The analysis involved data from 9,176 adults who participated in the 2003–2018 study period. The researchers compared clinical variables with smoking-related factors, including the duration of smoking and the levels of carbon monoxide, nicotine, and tar.

The study result revealed that tobacco, which is primarily composed of nicotine, poses severe health risks, particularly to cardiovascular tissues. Nicotine activates neuronal nicotinic acetylcholine receptors (nAChRs), leading to the release of noradrenaline and adrenaline. This increases blood pressure and heart rate, thereby heightening the risk of stroke.

Additionally, nicotine enhances blood viscosity, which further increases the likelihood of thrombosis. Smoking generates carbon monoxide, which reduces the blood's oxygen-carrying capacity, leading to hypoxia in various tissues and organs, especially the brain.

The combustion of tobacco produces tar, a complex mixture of harmful substances such as polycyclic aromatic hydrocarbons (PAHs), heavy metals, and free radicals. These compounds contribute to stroke risk by damaging vascular endothelial cells, reducing nitric oxide production, and increasing oxidative stress.

Reference: Wang, Y., Ge, Y., Yan, W. et al. (2024) From smoke to stroke: quantifying the impact of smoking on stroke prevalence. BMC Public Health 24, 2301. doi:https://doi.org/10.1186/s12889-024-19754-6. https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-024-19754-6

A major Chandipura Virus(CHPV) Outbreak has been reported in the Gujrat State of India, which is considered the largest in 20 years, WHO recently stated.

CHPV is a virus from the Rhabdoviridae family that causes sporadic cases and outbreaks of acute encephalitis syndrome (AES) in parts of India, especially during the rainy season. It spreads through insects like sandflies, mosquitoes, and ticks. In Gujarat, the sandfly Phlebotomus papatasi is known to carry the virus. The disease often has a high death rate, ranging from 56% to 75%, especially during outbreaks in India.

As per the WHO, from early June to August 15, 2024, the Ministry of Health and Family Welfare of India reported 245 cases of acute encephalitis syndrome (AES), with 82 of those cases resulting in death, giving a case fatality rate of 33%.

Out of the 245 reported cases of acute encephalitis syndrome (AES), 64 have been confirmed cases caused by CHPV. Among these 64 confirmed cases, 61 were reported in Gujarat State and 3 in Rajasthan State.

Since July 19, 2024, there has been a daily decrease in the number of new AES cases.

In 2003, a significant outbreak of acute encephalitis syndrome (AES) occurred in Andhra Pradesh, with 329 suspected cases and 183 deaths. A study suggests that this outbreak was caused by CHPV.

CHPV infection leads to a quick onset of symptoms and has a high case-fatality rate, ranging from 56% to 75%. There is currently no specific treatment or vaccine for the virus, so care is focused on managing symptoms. Prompt referral of suspected AES cases to specialized facilities can enhance the chances of a better outcome.

“To prevent the spread of CHPV, controlling vectors and protecting against bites from sandflies, mosquitoes, and ticks are crucial measures. Poor housing and sanitation, such as inadequate waste management or open sewers, can create breeding and resting sites for sandflies and increase their access to humans,” WHO suggested.

While there are no specific antiviral treatments or approved vaccines for CHPV, early medical intervention and supportive care can enhance the chances of a better outcome.

Reference: World Health Organization. (2024). Acute encephalitis syndrome due to Chandipura virus. https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON529.