Category: Ageing

Recreational Substances Including Cannabis Linked to Heart Disease

Alcohol, tobacco and cannabis are among recreational drugs that contribute to early-onset atherosclerotic cardiovascular disease (ASCVD) in young people, a study has found.

The study drew on data of more than a million people receiving primary care services throughout the VA Healthcare System in 2014 or 2015, of whom there were 135 703 with premature ASCVD.

A number of independent predictors for first-event ASCVD for men (from age 55) and women (from 65) were picked up. Tobacco (adjusted odds ratio [OR] 1.97) and alcohol use (OR 1.50)  conferred significant additional risk, but the greatest risk increase of generally legal substances was cannabis use (OR 2.65). Cocaine use (OR 2.44), amphetamine use (OR 2.74) and other drug use (OR 2.53) all had very high risk increases.

Those using four or more substances had the greatest risk at nearly nine times normal. Women also had much stronger effect sizes for premature ASCVD than men.

In an accompanying editorial Anthony Wayne Orr, PhD, and colleagues at LSU Health Shreveport, wrote: “Substance use disorders have been associated with an acceleration of the ageing process. We are only young once, and we should do everything in our power to maintain that state as long as we can.”

The editorialists suggested a nationwide ASCVD education campaign targeting people with substance use disorders.

“In addition, clinicians and primary care providers should begin screening their adult and young adult patients with a history of a substance use disorder for symptoms of premature or extremely premature ASCVDs at earlier stages in their patients’ lives,” suggested the editorialists.

Limitations included it being an observational study, lack of socioeconomic data and the cohort being mostly white males, as well as not being able to discern between prescription and recreational amphetamine use.
“Retrospective studies are limited by the available data. While this study supports the association between substance use disorder and early-onset ASCVD, the effect of substance use frequency, dose, and duration cannot be reliably ascertained in this patient sample,” the editorialists stated.

The editorialists recommended that specific biomarkers for substance use-associated cardiovascular disease be identified, and therapeutic window characterised to limit these chronic effects of substance use disorder.

Source: MedPage Today

Journal information: Mahtta D, et al “Recreational substance use among patients with premature atherosclerotic cardiovascular disease” Heart 2021; DOI: 10.1136/heartjnl-2020-318119.

Editorial information: Scott ML, et al “Young at heart? Drugs of abuse cause early-onset cardiovascular disease in the young” Heart 2021; DOI: 10.1136/heartjnl-2020-318856.

Europe’s Oldest Living Person, 116, Survives COVID

A 116 year old French nun who is Europe’s oldest living person has survived COVID after testing positive.

French nun Sister Andrée had tested positive for COVID in her retirement home in Toulon, but had remained symptom-free. Most of the 88 residents at the home contracted the virus, 10 of whom died. 

Sister Andrée, who is blind and in a wheelchair, said that her main complaint was the solitude necessitated by being confined to her room.
“I didn’t even realise I had it,” she told Var-Matin newspaper:

David Tavella, a spokesperson for the nursing home, told the newspaper that she had no fear of the virus.

“She didn’t ask me about her health but about her routine. She wanted to know for example if the meal and bed times were going to change. She showed no fear of the illness, in fact she was more worried about the other residents,” Mr Tavella said.

When asked by France’s BFM Television if she had been scared of having COVID, she responded: “No, I wasn’t scared because I wasn’t scared to die … I’m happy to be with you, but I would wish to be somewhere else – join my big brother and my grandfather and my grandmother.”

In addition to being Europest oldest living person, she is also the world’s second oldest living person. The oldest living person in the world is Kane Tanaka in Japan, who turned 118 on January 2. Having lived through the First World War as a child, Sister Andrée will turn 117 on Thursday.

Source: The Guardian

Legendary Singer Tony Bennett Diagnosed with Alzheimer’s

Music legend Tony Bennett, 94, revealed in an interview that he was diagnosed with Alzheimer’s disease 4 years ago.

The singer’s career has spanned seven decades, he had continued his initial success in the 1950s across multiple genres, becoming a hit with the MTv generation, and in more recent years collaborating with popular artists like Amy Winehouse and Lady Gaga.

Alzheimer’s disease is an age-related, irreversible neurodegenerative condition. In more than 90% of patients, it begins after age 65, although it can occur as early as in the 30s. It is marked by memory loss and confusion that seem like the normal cognitive decline of older age, but it is more rapid and severe, eventually resulting in death. As people live longer and the risks of developing this disease increase with age, the burden of this disease is expected to increase in the future. In the US, the number of people with Alzheimer’s is expected to nearly triple from 5.5 million to 14 million by 2060.

Mr Bennett has been able to work over the past four years but the toll is perceptible. He still recognises his family members but his short-term and long-term memory have drastically deteriorated. Interviewer John Colapinto noted Mr Bennett gazing at his lavishly illustrated book, “Tony Bennett Onstage and in the Studio” (2018). “He stared into its pages not with the air of warm reminiscence but like a man struggling to recall why these images seemed familiar.” His wife, Susan, added that Mr Bennett is “not always sure where he is or what is happening around him. Mundane objects as familiar as a fork or a set of house keys can be utterly mysterious to him.”

Over the past two years, Mr Bennett recorded a second album of duets with Lady Gaga, a follow-up to the hit album with Gaga in 2014. While he had been known to be a “meticulous and hard-driving perfectionist in the studio,” Mr Bennett was much more subdued. speaking rarely, his words coming haltingly and seeming lost or bewildered. Gaga, who considers Mr Bennett to be “an incredible mentor, and friend, and father figure” is seen breaking down in tears as Tony sings a solo passage of a love song.

The album is due to be released this spring, but Mr Bennett will be unable to do promotional interviews. Mr Bennett, together with his wife and son (who is also his manager) decided to break the news, in the hopes that as many fans as possible know about what will likely be his final record. The neurologist who diagnosed Bennett in 2016,  Gayatri Devi, MD, said: “He is doing so many things, at 94, that many people without dementia cannot do. He really is the symbol of hope for someone with a cognitive disorder.”

Source: MedPage Today

Cannabis can Lower Hypertension in Older Adults

Adding to a growing body of evidence as to its health benefits, medical cannabis may lower blood pressure in older adults, according to research from Ben-Gurion University of the Negev (BGU) and its affiliated Soroka University Medical Center.

This is the first such study to investigate cannabis’  effect on blood pressure, heart rate and metabolic parameters in hypertensive adults 60 and older.

“Older adults are the fastest growing group of medical cannabis users, yet evidence on cardiovascular safety for this population is scarce. This study is part of our ongoing effort to provide clinical research on the actual physiological effects of cannabis over time,” said Dr Ran Abuhasira, BGU Faculty of Health Sciences and BGU-Soroka Cannabis Clinical Research Institute

Before and three months after beginning medical cannabis therapy, patients in the study were evaluated using 24-hour ambulatory blood pressure monitoring, ECG, blood tests, and body measurements. Patients ingested cannabis either orally in the form of oil extracts or by smoking.

The findings included a significant drop in 24-hour systolic and diastolic blood pressure values, with the lowest point occurring three hours after ingesting cannabis. Both daytime and nighttime reductions in blood pressure were observed, with more greater changes at night. Higher nighttime than daytime blood pressure may also raise the risk of Alzheimer’s disease, so lowering it at night may offer that benefit.

The pain relief from taking cannabis, often a reason for prescriptions, may also have resulted in a reduction of blood pressure, the BGU researchers postulated.

“Cannabis research is in its early stages and BGU is at the forefront of evaluating clinical use based on scientific studies,” said Doug Seserman, chief executive officer of American Associates, BGU. “This new study is one of several that has been published recently by BGU on the medicinal benefits of cannabis.”

Source: News-Medical.Net

Journal information: Abuhasira, R., et al. (2021) Cannabis is associated with blood pressure reduction in older adults – A 24-hours ambulatory blood pressure monitoring study. European Journal of Internal Medicine.doi.org/10.1016/j.ejim.2021.01.005.

APLS1 Inhibitors Eliminate Senescent Cells to Ameliorate Ageing

A new technique has been developed to eliminate senescent cells that are involved in many age-related diseases, according to a study by researchers at the University of Tokyo.

As ageing progresses, cancers emerge, motor function declines through muscle loss, and metabolic disorders occur due to adipose tissue atrophy. Senescent cells accumulating in organs are behind many of these problems; their telomeres having shortened through divisions as a result of multiple stresses and now at their replication limit, they now no longer function effectively. Previous research using genetic engineering to knock out senescent cells in mice was able to put the onset of age-related diseases such as arteriosclerosis and renal damage, and extended life expectancy. However, the research did not yield a drug which could be given as a treatment.

To tackle this problem, the researchers created a way to produce large numbers of purified senescent. cells to search for genetic targets for drugs. One of the ways they found involved GLS1, a gene involved in glutamine. On testing with GLS1 inhibitors, senescent cells were vulnerable due to damage to the lysosomal membrane and lower intracellular pH. Lysosomes are organelles which produce enzymes to destroy defunct cell parts, bacteria and viruses if needed, and the cell itself if apoptosis is triggered. They also have an essential role in the regulation of intracellular pH, and are very acidic, having to be protected from the rest of the cell by a membrane. Analysing the dynamics of lysosomes, the team found that damage to the lysosomal membranes in senescent cells decreases intracellular pH.

When they administered GLS1 inhibitors to old mice, knocking out senescent cells, their ageing was significantly improved. The symptoms of obese diabetes, arteriosclerosis, and fatty liver disease were ameliorated. GLS1 inhibitors are already being used in trials as cancer treatments.
“We hope that innovative anti-aging therapies and treatments for geriatric diseases will be developed that can remove senescent cells by treatment with GLS1 inhibitors,” said Professor Nakanishi.

Source: News-Medical.Net

Journal information: Johmura, Y., et al. (2021) Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science. doi.org/10.1126/science.abb5916.

Anti-HIV Drugs may Combat Macular Degeneration

New research has shown that anti-HIV drugs may fight macular degeneration – overturning a preconception about DNA in the process.

Macular degeneration is the leading cause of blindness in developed countries. Even though HIV does not cause dry macular degeneration, the drugs prevented the loss of vision.

“We are extremely excited that the reduced risk was reproduced in all the databases, each with millions of patients,” said Jayakrishna Ambati, MD, a leading macular degeneration researcher at the University of Virginia School of Medicine. “This finding provides real hope in developing the first treatment for this blinding disease.”

A Big Data Archeology review of four health insurance databases showed that Nucleoside Reverse Transcriptase Inhibitors (NRTIs), a commonly used HIV treatment, reduced the incidence of dry macular degeneration by 40%. The records spanned two decades and covered over 100 million patients. The drugs had also previously been shown to possibly prevent diabetes.

The finding also comes with the discovery that DNA can be produced inside the cytoplasm. Alu DNA (found exclusively in primates), which makes up 10% of the human genome, is transposable and can insert itself into other places on the genome. It was long considered “junk” DNA, but are now believed to have important functions, such as allowing for multiple expressions of proteins from a single Alu element. Since it cannot replicate itself, Alu DNA requires a transposon called L1 to accomplish this, which was now reported to allow the production of Alu DNA outside the chromosome. The buildup of Alu DNA in cells contributes to macular degeneration, by killing off cells that support the retina.
The researchers are urging further investigation into NRTIs or safer derivatives known as Kamuvudines, both of which block a key inflammatory pathway, can be useful in preventing vision loss from dry macular degeneration.

“A clinical trial of these inflammasome-inhibiting drugs is now warranted,” said Ambati. “It’s also fascinating how uncovering the intricate biology of genetics and combining it with big data archeology can propel insights into new medicines.”

Source: Medical Xpress

Journal Information: Shinichi Fukuda el al., “Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.202275111

Obesity Adds to Alzheimer Severity

In addition to it being a risk factor for many known chronic diseases, obesity is an additional burden on cerebral health and may also be associated with the progression of Alzheimer’s disease, according to a new study from the University of Sheffield and the University of Eastern Finland.  

The study used multimodal neural imaging and showed that obesity may contribute to the vulnerability of neural tissue, while maintaining a healthy weight helped to maintain brain structure in mid dementia Alzheimer’s disease.

Alzheimer’s disease is a neurodegenerative disease which accounts for two thirds of dementia in over 65s, is the sixth leading cause of death in the United States and there is no cure at present.  

Lead author Professor Annalena Venneri from the University of Sheffield’s Neuroscience Institute and NIHR Sheffield Biomedical Research Centre, said: “More than 50 million people are thought to be living with Alzheimer’s disease and despite decades of ground breaking studies and a huge global research effort we still don’t have a cure for this cruel disease.

“Prevention plays such an important role in the fight against the disease. It is important to stress this study does not show that obesity causes Alzheimer’s, but what it does show is that being overweight is an additional burden on brain health and it may exacerbate the disease.”

She added that it was important to educate people early on in their lives as it was too late to wait until the 60s to lose weight as the disease lurks in the backgrounds.

The researchers examined MRI scans of the brains of 47 patients diagnosed with mild Alzheimer’s disease dementia, 68 patients with mild cognitive impairment, and 57 individuals who were cognitively healthy. Using three complementary, computational techniques, they studied the brain’s anatomy, blood flow and also the brain’s fibres.

They compared gray matter volume, white matter integrity, cerebral blood flow and obesity. Grey matter volume decreases in Alzheimer’s. In patients with mild Alzheimer’s, an association was found with obesity and grey matter volume around the right temporoparietal junction, suggesting obesity creates a neural vulnerability in cognitively impaired patients. The study also found that maintaining a healthy weight may help preserve brain structure in structure in the presence of age and disease-related weight loss.

Joint author Dr Matteo De Marco from the University of Sheffield’s Neuroscience Institute, said: “Weight-loss is commonly one of the first symptoms in the early stages of Alzheimer’s disease as people forget to eat or begin to snack on easy-to-grab foods like biscuits or crisps, in place of more nutritional meals.

“We found that maintaining a healthy weight could help preserve brain structure in people who are already experiencing mild Alzheimer’s disease dementia. Unlike other diseases such as cardiovascular disease or diabetes, people don’t often think about the importance of nutrition in relation to neurological conditions, but these findings show it can help to preserve brain structure.”

Source: Medical Xpress

Journal information: Manmohi D. Dake et al, Obesity and Brain Vulnerability in Normal and Abnormal Aging: A Multimodal MRI Study, Journal of Alzheimer’s Disease Reports (2021). DOI: 10.3233/ADR-200267

New Study Has Good and Bad News on TIAs

There is both good and news on transient ischaemic attacks (TIAs) from a more than six-decade long study: TIAs are indeed harbingers of strokes, but also the incidence of post-TIA strokes has been falling over the decades.

A TIA is defined as a passing episode of neurologic dysfunction due to the focal brain, spinal cord, or retinal ischaemia, without acute infarction or tissue injury. The results were derived from the Framingham Heart Study had 14 059 participants and ran for over six decades, allowing for a more-complete picture of strokes that happen after a TIA. Of the participants, 435 had a TIA; these were compared against a second group of 2175 participants who did not have a TIA.

Even after accounting for other risk factors such as hypertension or diabetes, people who had experienced a TIA had a 4.5 to five times greater chance of a stroke. Study lead author Vasileios-Arsenios Lioutas, MD, said that the results show a need for intensive follow-up of TIA : “According to our findings, people continue to have a high risk of stroke for a sustained time after they’ve had a TIA. Therefore, one shouldn’t think that the high-risk period is just in the first 90 days after the attack and then one can relax. It seems these patients should be followed closely over time, keeping in mind that they are at risk for stroke and paying close attention to controlling their cardiovascular risk factors.”

The 66 years of study data was broken into three epochs. One- and five-year risks of post-TIA stroke in the 2000-2017 epoch were 7.6% and 16.1%, compared to 23.9% and 35.5% during the earliest epoch, from 1948 to 1985.

Sudha Seshadri, MD, professor of neurology at The University of Texas Health Science Center at San Antonio, said: “We examined 66 years of follow-up from Framingham participants, which allowed us to study trends over time. We can see that starting in the very early years of the Framingham study, the 1950s, moving on to the most recent times, the risk of subsequent stroke went down a lot.”

Source: News-Medical.Net

Journal information: Lioutas, V-A., et al. (2021) Incidence of Transient Ischemic Attack and Association With Long-term Risk of Stroke. JAMA.doi.org/10.1001/jama.2020.25071.

For Older IBD Patients, Vedolizumab is a Safer Option

Vedolizumab appeared to be safer than tumour necrosis factor (TNF) inhibitors in older adults with inflammatory bowel disease (IBD), according to the results of a large retrospective study.

Vedolizumab is a fully humanised monoclonal antibody which targets α4β7 integrin, and prevents leukocyte movement from the blood into inflamed gut tissue.

At the virtual Crohn’s and Colitis Congress, Bharati Kochar, MD, of Massachusetts General Hospital in Boston, presented data showing that all-cause hospitalisation during the 12 months after initiating biologic treatment was lower in new users of vedolizumab than in those starting TNF inhibitors, with a hazard ratio of 0.81 (95% CI 0.68-0.96)

“The American population is rapidly aging, and the number of Americans 65 and older in 2060 will be more than double what it was in 2014,” Dr Kochar said. “The combination of increasing IBD incidence, improvements in disease treatment-related knowledge, and decreasing IBD mortality is resulting in a high prevalence of older adults with IBD,” she added.

It is estimated that a quarter of Americans over 65 have IBD, yet are less likely to receive adequate immunosuppression. Over 65s are underrepresented in IBD clinical trials, creating a lack of understanding over what medications work or not in this age group.

To answer this question, Dr Kochar and her team analysed a 20% sample of Medicare claims database. Patients were included if they were diagnosed with Crohn’s disease or ulcerative colitis and if they initiated treatment with vedolizumab, infliximab, adalimumab, golimumab, or certolizumab from 2014 to 2018 after being on Medicare for 12 months while not receiving any of those medications.

There were 488 new users of vedolizumab and 2213 initiators of TNF inhibitors in the analysis group, with an average age of 71. More than half were women and most were white, 44% had ulcerative colitis and over half of patients had Carlson Comorbidity Index scores of 2 or higher.

There was otherwise no significant difference between vedolizumab and TNF for IBD-related hospitalisation (HR 0.77, 95% Ci 0.53-1.12), IBD-related surgery: (HR 0.78, 95% CI 0.49-1.22), or new steroid prescription within 60 days of starting the biologic (HR 1.01, 95% CI 0.86-1.18).

In the 6-month period prior to biologic initiation, nearly one-third had a prescription for budesonide, 58% had a prescription for a systemic corticosteroid, and nearly one-third were being prescribed immunomodulators.

“In conclusion, I think it’s important to use your clinical judgment to treat the patient in front of you, and these data should simply help contextualise risk for older IBD patients newly initiating vedolizumab or TNF inhibitors,” said Dr Kochar.

“There is a vast need for additional large and robust comparative effectiveness and safety studies for older adults with IBD, with the rapid proliferation of new IBD medications,” she concluded.

Source: MedPage Today

Presentation information: Kochar B, et al “Comparative effectiveness and safety of vedolizumab and anti-tumor necrosis factor agents in older adults with inflammatory bowel diseases in Medicare administrative claims database” CCC 2021

Aspirin Protects against Colorectal Cancer

Aspirin is known to reduce the risk of colorectal cancer in middle-aged adults and up until age 70, but has some risky side effects, such as colorectal bleeding. 

It was not known at what stage it was still worth it to start taking aspirin. Indeed, the recent Aspirin in Reducing Events in the Elderly (ASPREE) trial reported that participants taking a daily dose of aspirin (100mg) after the age of 70 for five years had a 30% increased risk of cancer mortality.
It is also currently recommended by the US Preventive Services Task Force that people aged 50-59 years with specific cardiovascular risk profiles take aspirin for its protective effect against heart disease.

To answer the question of whether aspirin was beneficial or harmful after age 70, Andrew T Chan MD, MPH, a gastroenterologist and chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital (MGH), led a team of researchers that analysed a pair of large cohort studies.These were The Nurses’ Health Study (January 1980 – June 2014) and the Health Professionals Follow-up Study (January 1986 – January 2014), giving them a total of 94 500 participants over 35 years.

Their findings showed that aspirin could indeed protect adults over 70 from colorectal cancer – with the caveat that the protection only applied if they started taking aspirin before the age of 70.”There is considerable evidence that aspirin can prevent colorectal cancer in adults between 50 and 70 years old,” commented Chan. “But it has not been clear whether the effect is similar in older adults.”

The researchers concluded that their results “strongly suggest that there is a potential biological difference in the effect of aspirin at older ages which requires further research.”

Source: News-Medical.Net