Medical Bulletin 08/ July/ 2024

Here are the top medical news for the day:

Smoking Identified as Major Contributor to Cognitive Decline in Older Adults: Study

Smoking may be among the most important lifestyle factors affecting how quickly cognitive skills decline as we age, suggested a new study led by UCL researchers.

The study was published in the journal Nature Communications.

Smoking has severe impacts on health, affecting nearly every organ in the body. It is a major cause of cardiovascular diseases, including heart attacks and strokes, and significantly increases the risk of various cancers, particularly lung cancer. Smoking also damages the respiratory system, leading to chronic obstructive pulmonary disease (COPD) and other breathing issues. Additionally, it accelerates cognitive decline, contributing to memory loss and dementia in older adults. The harmful chemicals in cigarettes weaken the immune system, reduce overall life expectancy, and negatively impact quality of life.

In the study, researchers analysed data from 32,000 adults aged 50 and over who participated in surveys over a 10-year period. The study aimed to explore how different combinations of health-related behaviours—smoking, physical activity, alcohol consumption, and social contact—affect cognitive decline in healthy older adults.

Cognitive function was measured using memory and verbal fluency tests. Participants were categorised into different lifestyle groups based on their behaviours: whether they smoked, engaged in moderate and vigorous physical activity at least once a week, and their alcohol consumption levels.

The findings revealed that cognitive decline was significantly faster among those who smoked compared to non-smokers. Specifically, smoking lifestyles experienced cognitive scores that declined up to 85% more over 10 years than those of non-smoking lifestyles.

“Our study is observational so cannot definitively establish cause and effect, but it suggests smoking might be a particularly important factor influencing the rate of cognitive ageing. Previous evidence suggests individuals who engage in more healthy behaviours have slower cognitive decline; however, it was unclear whether all behaviours contributed equally to cognitive decline, or if there were specific behaviours driving these results. Our findings suggest that among the healthy behaviours we examined, not smoking may be among the most important in terms of maintaining cognitive function,” said the authors.

Reference: Bloomberg, M., Muniz-Terrera, G., Brocklebank, L. et al. Healthy lifestyle and cognitive decline in middle-aged and older adults residing in 14 European countries. Nat Commun 15, 5003 (2024). https://doi.org/10.1038/s41467-024-49262-5

Research Shows How Your Genes Could Predict Your Atrial Fibrillation Risk

Your genes influence your risk of developing the heart condition atrial fibrillation, a large-scale genetic survey has shown. This may prevent cases of atrial fibrillation and lead to better and more precise treatment.

Atrial fibrillation (AF) is a common heart rhythm disorder characterized by rapid and irregular beating of the atria, the upper chambers of the heart. This condition can lead to poor blood flow and increase the risk of stroke, heart failure, and other heart-related complications. Symptoms of AF may include palpitations, shortness of breath, and fatigue, though some individuals may be asymptomatic. Factors contributing to AF include age, high blood pressure, heart disease, and genetic predisposition.

Now researchers from the University of Copenhagen and Rigs Hospital studied the role of genetics on atrial fibrillation development and published their findings in the journal JAMA Cardiology.

In the study, researchers applied a genetic risk score for atrial fibrillation (AF) to over 400,000 individuals from the large, international UK Biobank. A genetic risk score is calculated based on known genetic variations that indicate a predisposition to atrial fibrillation. While some variations slightly increase the risk, others decrease it. Through computer calculations, the researchers assessed the significance of these common variations and determined each person's overall genetic risk for AF.

Additionally, the researchers examined the effect of rare genetic changes in nearly 18,000 different genes. They identified six genes where genetic changes significantly influence a person's risk of developing atrial fibrillation. Approximately one percent of the participants carried such rare genetic changes in one of these genes. When combined with their overall genetic risk, these changes could substantially increase their likelihood of developing atrial fibrillation.

“We can tell that those with a high genetic risk score for atrial fibrillation have significantly increased risk of developing the condition – especially if they also experience classic risk factors for atrial fibrillation such as hypertension and obesity. If you both have a high overall genetic risk score and changes in one of the identified genes, your risk of developing atrial fibrillation appears to be almost five times as high as usual,” said the researchers.

Reference: Vad OB, Monfort LM, Paludan-Müller C, et al. Rare and Common Genetic Variation Underlying Atrial Fibrillation Risk. JAMA Cardiol. Published online June 26, 2024. doi:10.1001/jamacardio.2024.1528

Study Discovers How Cancer Evades Chemotherapy, Identifies Mechanism to Reverse

An international team of researchers from the UK and China has uncovered how cancer develops resistance to chemotherapy, addressing one of the most significant challenges in treating this deadly disease.

The early-stage study, conducted using mice and led by The Institute of Cancer Research (ICR) in London and Sun Yat-sen University in China, demonstrated that Stiripentol, a drug currently used to treat epilepsy, can help counteract cancer's resistance to chemotherapy. This discovery could lead to more effective tumour reduction and improved survival rates for cancer patients.

The findings were published in the journal Nature.

Cancer cells exhibit two key characteristics: altered metabolism and genome instability. They change the way they take in and use nutrients to support continuous cell survival. Radiotherapy and most chemotherapy drugs aim to damage DNA, leading to cancer cell death. However, cancer cells must quickly repair this DNA damage to stay alive. Some accumulated metabolites, like 2-hydroxyglutarate, fumarate, and succinate, hinder DNA repair and increase genome instability. However, less is known about metabolites that aid DNA repair. Therefore, understanding how metabolism-driven DNA repair mechanisms support tumour survival is crucial.

In the study, the team focused on lactate, a byproduct that accumulates as cancer cells convert nutrients into energy. They found that lactate was most abundant in chemotherapy-resistant cancer tissues. Researchers examined tissue from 24 patients with stomach cancer, where 15 of the cancers were resistant to chemotherapy and continued to grow.

Using a mouse model, the researchers tested the combination of Stiripentol and chemotherapy. This treatment reduced tumour size for four weeks after treatment and extended survival in mice with stomach cancer to more than 70 days. In contrast, tumours in mice treated with chemotherapy alone shrank for only one week before regrowing, and none of these mice survived longer than 40 days after treatment.

Additionally, lactate was found to alter the structure of a key protein involved in DNA repair, called NBS1, affecting its efficiency.

“Lactate helps protect the genome and allows cancer cells to survive despite the damaging effects of chemotherapy. The findings showed that lactate enhances the DNA repair machinery and contributes to chemotherapy resistance. Chemotherapy is a key treatment for many cancers, but resistance to these drugs leads to many patient deaths. Our study reveals a strong synergy between the LDHA inhibitor stiripentol, a drug already used clinically, and chemotherapy treatments like cisplatin and radiation. This suggests that targeting lactate could be a promising strategy to improve chemotherapy effectiveness and increase survival rates for cancer patients,” said Professor Axel Behrens, Professor of Stem Cell Biology at The Institute of Cancer Research.

Reference: Chen, H., Li, Y., Li, H. et al. NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance. Nature (2024). https://doi.org/10.1038/s41586-024-07620-9