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Drinking any amount of alcohol likely increases dementia risk

Even light drinking—generally thought to be protective, based on observational studies—is unlikely to lower the risk, which rises in tandem with the quantity of alcohol consumed.

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Drinking any amount of alcohol likely increases the risk of dementia, suggests the largest combined observational and genetic study to date, published online in BMJ Evidence Based Medicine.

Even light drinking—generally thought to be protective, based on observational studies—is unlikely to lower the risk, which rises in tandem with the quantity of alcohol consumed, the research indicates.

Current thinking suggests that there might be an ‘optimal dose’ of alcohol for brain health, but most of these studies have focused on older people and/or didn’t differentiate between former and lifelong non-drinkers, complicating efforts to infer causality, note the researchers.

To try and circumnavigate these issues and strengthen the evidence base, the researchers drew on observational data and genetic methods (Mendelian randomisation) from two large biological databanks for the entire ‘dose’ range of alcohol consumption.

These were the US Million Veteran Program (MVP), which includes people of European, African, and Latin American ancestry, and the UK Biobank (UKB), which includes people of predominantly European ancestry.

Participants who were aged 56–72 at baseline, were monitored from recruitment until their first dementia diagnosis, death, or the date of last follow-up (December 2019 for MVP and January 2022 for UKB), whichever came first. The average monitoring period was 4 years for the US group, and 12 for the UK group. 

Alcohol consumption was derived from questionnaire responses—over 90% of participants said they drank alcohol—and the Alcohol Use Disorders Identification Test (AUDIT-C) clinical screening tool. This screens for hazardous drinking patterns, including the frequency of binge drinking (6 or more drinks at a time).

In all, 559,559 participants from both groups were included in observational analyses, 14,540 of whom developed dementia of any type during the monitoring period:10,564 in the US group; and 3976 in the UK group. And 48,034 died: 28,738 in the US group and 19,296 in the UK group. 

Observational analyses revealed U-shaped associations between alcohol and dementia risk: compared with light drinkers (fewer than 7 drinks a week) a 41% higher risk was observed among non-drinkers and heavy drinkers consuming 40 or more drinks a week, rising to a 51% higher risk among those who were alcohol dependent. 

Mendelian randomisation genetic analyses drew on key data from multiple large individual genome-wide association studies (GWAS) of dementia, involving a total of 2.4 million participants to ascertain lifetime (rather than current) genetically predicted risks.

Mendelian randomisation leverages genetic data, minimising the impact of other potentially influential factors, to estimate causal effects: genomic risk for a trait (in this case, alcohol consumption) essentially stands in for the trait itself. 

Three genetic measures related to alcohol use were used as different exposures, to study the impact on dementia risk of alcohol quantity, as well as problematic and dependent drinking. 

These exposures were: self-reported weekly drinks (641 independent genetic variants);  problematic ‘risky’ drinking (80 genetic variants); and alcohol dependency (66 genetic variants). 

Higher genetic risk for all 3 exposure levels was associated with an increased risk of dementia, with a linear increase in dementia risk the higher the alcohol consumption. 

For example, an extra 1-3 drinks a week was associated with a 15% higher risk. And a doubling in the genetic risk of alcohol dependency was associated with a 16% increase in dementia risk.

But no U-shaped association was found between alcohol intake and dementia, and no protective effects of low levels of alcohol intake were observed. Instead, dementia risk steadily increased with more genetically predicted drinking. 

What’s more, those who went on to develop dementia typically drank less over time in the years preceding their diagnosis, suggesting that reverse causation—whereby early cognitive decline leads to reduced alcohol consumption—underlies the supposed protective effects of alcohol found in previous observational studies, say the researchers.

They acknowledge that a principal limitation of their findings is that the strongest statistical associations were found in people of European ancestry, because of the numbers of participants of this ethnic heritage studied. Mendelian randomisation also relies on assumptions that can’t be verified, they add.

Nevertheless, they suggest that their findings “challenge the notion that low levels of alcohol are neuroprotective.”

And they conclude: “Our study findings support a detrimental effect of all types of alcohol consumption on dementia risk, with no evidence supporting the previously suggested protective effect of moderate drinking. 

“The pattern of reduced alcohol use before dementia diagnosis observed in our study underscores the complexity of inferring causality from observational data, especially in ageing populations. 

“Our findings highlight the importance of considering reverse causation and residual confounding in studies of alcohol and dementia, and they suggest that reducing alcohol consumption may be an important strategy for dementia prevention.”

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Common drug class may increase risk of heart disease

The risk of cardiovascular disease increased in line with how much anticholinergic medication the participants used each year. Those with the highest exposure had a 71 per cent higher risk of a cardiovascular event than people who did not use anticholinergic medication at all.

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People who use drugs with anticholinergic effects, including certain antidepressants, drugs for urinary incontinence and common antihistamines, are at higher risk of developing cardiovascular disease.

This is shown in a study from Karolinska Institutet published in BMC Medicine.

Anticholinergic drugs reduce the effect of the neurotransmitter acetylcholine and are commonly prescribed to middle-aged and older people. This large group of drugs includes antihistamines used for allergic conditions, anxiety or insomnia, drugs for urinary incontinence, and certain antidepressants, where tricyclic antidepressants have a strong anticholinergic effect, whereas SSRIs have a weaker effect. A high cumulative use of these drugs, referred to as anticholinergic burden (see fact box), has previously been linked to impaired cognitive ability. 

May affect heart regulation 

The new study suggests that the drugs may also affect the parasympathetic nervous system and thereby the regulation of the cardiovascular system. The results show that it may be important to monitor the total drug burden in everyday clinical practice.

The study included more than 500,000 people in Stockholm, Sweden, who were 45 years of age or older and had no prior cardiovascular disease, except for hypertension, at the start of the study. The researchers followed the participants for up to 14 years and analysed how the use of anticholinergic drugs was associated with the development of cardiovascular disease.

“Many of these drugs are used by older people and by people with multiple medical conditions. We wanted to investigate whether the total exposure had any significance for the risk of developing cardiovascular disease over time,” says Nanbo Zhu, postdoctoral researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

71 per cent higher cardiac risk

The study showed that the risk of cardiovascular disease increased in line with how much anticholinergic medication the participants used each year. Those with the highest exposure had a 71 per cent higher risk of a cardiovascular event than people who did not use anticholinergic medication at all. The association was seen for all types of cardiovascular disease but was particularly clear for heart failure and various forms of arrhythmia.

“Our results indicate that the cumulative drug burden can affect heart regulation, not only in the short term but also over the long term. This does not mean that the drugs should always be avoided, but that exposure should be monitored carefully,” says Hong Xu, assistant professor at the Department of Neurobiology, Care Sciences and Society.

The researchers point out that the study is observational, meaning it cannot establish a causal relationship. Other factors, such as underlying diseases, may also influence the associations.

The work was carried out within the Stockholm CREAtinine Measurements project in collaboration between several research groups at Karolinska Institutet and Region Stockholm. The study was funded by the Swedish Research Council, the Center for Innovative Medicine Foundation, and other foundations. Some researchers report assignments for the pharmaceutical industry, which are disclosed in the scientific publication.

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Mindfulness practices found to significantly reduce depression symptoms, especially for those with early-life adversity

Mindfulness interventions help by regulating our emotions better when different challenges come up. For someone who has experienced childhood neglect or abuse, mindfulness training can help us make sense of that and respond skillfully to this moment in time.

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A new study reveals that mindfulness practices may significantly reduce depression symptoms, particularly in people who have experienced early-life adversity, such as childhood abuse and neglect.

Led by Eric Loucks, professor of medicine, epidemiology, and of behavioral and social sciences and director of the Mindfulness Center at Brown, the study enrolled 201 participants, 101 of whom were randomized into the Mindfulness-Based Blood Pressure Reduction Program, while 100 were randomized into an enhanced usual care control, which included home blood-pressure monitors, physician access and health-education materials. Researchers also had a measure of participants’ early-life adversity, particularly their exposure to abuse or neglect.

Loucks and his team followed participants for six months to assess changes in blood pressure, health behaviors and mental health, finding that those in the mindfulness program showed significant improvements in their depression symptoms. Additionally, participants who experienced childhood neglect showed greater improvements in depression symptoms than those who had not. A similar, though less pronounced, trend was observed among people with a history of childhood abuse.

“In this program, that was primarily designed to lower blood pressure while addressing whole-person health, we also saw that mental well-being, particularly around depression symptoms, improved in participants that went through the program,” Loucks said. “The findings suggest that cultivating mindful self-regulation skills–such such as self-awareness, attention control and emotion regulation–may help interrupt maladaptive patterns shaped by past experiences.”

Over the last 15 years, Loucks has been studying social determinants of health such as early-life adversity and its impacts on cardiovascular health, body mass index and blood pressure. “I came to a point where I wanted to not just document it, but do something about it, and I wondered if mindfulness training might help,” he said. “I’d gone through a lot of mindfulness training myself outside of work and started to get trained up in mindfulness programs that are specific to health contexts.”

Loucks began to study the Mindfulness-Based Stress Reduction program, running it through two clinical trials that were funded by the NIH and finding that it reduced blood pressure in both trials. He also wanted to look at the intervention from a whole-person perspective.

“If we look at everyday folks out in the world, those that had exposure to early life adversity, like abuse and neglect, tend to have worse mental health and also worse cardiovascular health,” Loucks said. “Mindfulness interventions help by regulating our emotions better when different challenges come up. For someone who has experienced childhood neglect or abuse, mindfulness training can help us make sense of that and respond skillfully to this moment in time.” 

Loucks discussed this work during a keynote address at the U.S. DOHaD Society this year. “It felt like a coming-home moment to see that this intervention, originally developed to address psychosocial factors that influence health, had even stronger effects among people with early-life adversity, particularly on depression,” he said. “It’s been about a 15-year arc of research that culminated in these findings.”

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High-fiber diet linked to reduced risk of heart disease in night shift workers

A moderate intake of about 19 grams of fibre per day was linked to a lower risk for those who worked night shifts regularly. For those who worked night shifts sporadically, about 15 grams was enough. The current recommendation for adults is about 25 grams of dietary fibre per day.

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People who work at night have a higher risk of coronary artery disease, a type of heart disease. A new study suggests that a higher fibre intake in the diet may help reduce this risk. The study included over 220,000 adults in the UK and is published in the European Journal of Epidemiology.

The human body is built to sleep at night. This means that working during the night goes against this natural pattern, and can place additional strain on the body, including the heart. Previous research has linked night work to an increased risk of coronary artery disease. Since night work is often unavoidable, the researchers wanted to investigate whether certain dietary habits might have a protective effect.

More fibre associated with lower risk

The researchers used data from 220,000 adults in the UK Biobank (2006–2010) and divided the participants into three groups:

  • Day workers
  • Shift workers who worked night shifts sporadically
  • Regular night shift workers

The participants had completed a detailed questionnaire about their dietary habits. During a follow-up after about 12 years, it was found that night shift workers who consumed little fibre in their diet had a higher risk of coronary artery disease than those who consumed more fibre.

“A moderate intake of about 19 grams of fibre per day was linked to a lower risk for those who worked night shifts regularly. For those who worked night shifts sporadically, about 15 grams was enough. The current recommendation for adults is about 25 grams of dietary fibre per day,” says Diana Nôga, lead author and researcher at Uppsala University.

The researchers stress that the figures from the study are not official dietary recommendations. But they do show a pattern in this UK study: a higher dietary fibre intake was linked to a lower risk of heart disease among night shift workers.

“The link between fibre and a lower risk of heart disease is not just because those who eat more fibre generally have a healthier lifestyle. We know this because we adjusted for various lifestyle factors in the analysis. One possible explanation, supported by previous research, is that fibre in the diet can improve intestinal flora and also reduce lipids, which can be particularly good for the heart in people who work at night,” says Christian Benedict, senior author of the study and Professor of Pharmacology at Uppsala University.

Dietary fibre can support heart health

According to the researchers, an increased intake of fibre-rich foods such as whole grains, vegetables, fruit, legumes and lentils may be a simple way to improve heart health for night shift workers. However, this requires that you do not have any medical obstacles to doing this, such as chronic gastrointestinal diseases.

“Dietary changes should be seen as a complement to, not a substitute for, other heart health-promoting habits such as not smoking, remaining physically active, and getting enough sleep,” says Diana Nôga.

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