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Repetitive negative thinking linked to dementia risk

Persistently engaging in negative thinking patterns may raise the risk of Alzheimer’s disease, finds a new UCL-led study.

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Persistently engaging in negative thinking patterns may raise the risk of Alzheimer’s disease, finds a new UCL-led study.

In the study of people aged over 55, published in Alzheimer’s & Dementia, researchers found ‘repetitive negative thinking’ (RNT) is linked to subsequent cognitive decline as well as the deposition of harmful brain proteins linked to Alzheimer’s.

The researchers say RNT should now be further investigated as a potential risk factor for dementia, and psychological tools, such as mindfulness or meditation, should be studied to see if these could reduce dementia risk.

Lead author Dr Natalie Marchant (UCL Psychiatry) said: “Depression and anxiety in mid-life and old age are already known to be risk factors for dementia. Here, we found that certain thinking patterns implicated in depression and anxiety could be an underlying reason why people with those disorders are more likely to develop dementia.

“Taken alongside other studies, which link depression and anxiety with dementia risk, we expect that chronic negative thinking patterns over a long period of time could increase the risk of dementia. We do not think the evidence suggests that short-term setbacks would increase one’s risk of dementia.

“We hope that our findings could be used to develop strategies to lower people’s risk of dementia by helping them to reduce their negative thinking patterns.”

For the Alzheimer’s Society-supported study, the research team from UCL, INSERM and McGill University studied 292 people over the age of 55 who were part of the PREVENT-AD cohort study, and a further 68 people from the IMAP+ cohort.

Over a period of two years, the study participants responded to questions about how they typically think about negative experiences, focusing on RNT patterns like rumination about the past and worry about the future. The participants also completed measures of depression and anxiety symptoms.

Their cognitive function was assessed, measuring memory, attention, spatial cognition, and language. Some (113) of the participants also underwent PET brain scans, measuring deposits of tau and amyloid, two proteins which cause the most common type of dementia, Alzheimer’s disease, when they build up in the brain.

The researchers found that people who exhibited higher RNT patterns experienced more cognitive decline over a four-year period, and declines in memory (which is among the earlier signs of Alzheimer’s disease), and they were more likely to have amyloid and tau deposits in their brain.

Depression and anxiety were associated with subsequent cognitive decline but not with either amyloid or tau deposition, suggesting that RNT could be the main reason why depression and anxiety contribute to Alzheimer’s disease risk.

“We propose that repetitive negative thinking may be a new risk factor for dementia as it could contribute to dementia in a unique way,” said Dr Marchant.

The researchers suggest that RNT may contribute to Alzheimer’s risk via its impact on indicators of stress such as high blood pressure, as other studies have found that physiological stress can contribute to amyloid and tau deposition.

Co-author Dr Gael Chételat (INSERM and Université de Caen-Normandie) commented: “Our thoughts can have a biological impact on our physical health, which might be positive or negative. Mental training practices such as meditation might help promoting positive- while down-regulating negative-associated mental schemes.

“Looking after your mental health is important, and it should be a major public health priority, as it’s not only important for people’s health and well-being in the short term, but it could also impact your eventual risk of dementia.”

The researchers hope to find out if reducing RNT, possibly through mindfulness training or targeted talk therapy, could in turn reduce the risk of dementia. Dr Marchant and Dr Chételat and other European researchers are currently working on a large project to see if interventions such as meditation may help reduce dementia risk by supporting mental health in old age.

Fiona Carragher, Director of Research and Influencing at Alzheimer’s Society, said: “Understanding the factors that can increase the risk of dementia is vital in helping us improve our knowledge of this devastating condition and, where possible, developing prevention strategies. The link shown between repeated negative thinking patterns and both cognitive decline and harmful deposits is interesting although we need further investigation to understand this better. Most of the people in the study were already identified as being at higher risk of Alzheimer’s disease, so we would need to see if these results are echoed within the general population and if repeated negative thinking increases the risk of Alzheimer’s disease itself.

“During these unstable times, we are hearing from people every day on our Alzheimer’s Society Dementia Connect line who are feeling scared, confused, or struggling with their mental health. So it’s important to point out that this isn’t saying a short-term period of negative thinking will cause Alzheimer’s disease. Mental health could be a vital cog in the prevention and treatment of dementia; more research will tell us to what extent.”

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Popular prescription weight loss drugs linked to uncommon blinding condition

Patients prescribed semaglutide (as Ozempic or Wegovy) for diabetes or weight loss had a higher risk of having a potentially blinding eye condition called NAION than similar patients who had not been prescribed these drugs.

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A new study led by investigators from Mass Eye and Ear found that patients prescribed semaglutide (as Ozempic or Wegovy) for diabetes or weight loss had a higher risk of having a potentially blinding eye condition called NAION than similar patients who had not been prescribed these drugs.

Notably, the study found people with diabetes who had been prescribed semaglutide by their physician and then filled the prescription were more than four times more likely to be diagnosed with NAION. Those who were overweight or had obesity and prescribed this drug were more than seventimes more likely to get the diagnosis.

The study, which was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School,  published July 3rd in JAMA Ophthalmology.

“The use of these drugs has exploded throughout industrialized countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, the study’s corresponding author. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.” 

NAION is relatively rare, occurring up to 10 out of 100,000 people in the general population. NAION is the second-leading cause of optic nerve blindness (second only to glaucoma) and it is the most common cause of sudden optic nerve blindness. NAION is thought to be caused by reduced blood flow to the optic nerve head, with the consequence of permanent visual loss in one eye. According to Rizzo, the visual loss caused by NAION is painless and may progresses over many days before stabilizing, and there is relatively little potential for improvement. There are currently no effective treatments for NAION. 

The impetus for the study occurred in the late summer of 2023 when Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend — three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. The physicians observed all three were taking semaglutide.

This anecdotal recognition led the Mass Eye and Ear research team to run a backward-looking analysis of their patient population to see if they could identify a link between this disease and these drugs, which had been surging in popularity.

Semaglutide was developed to treat type 2 diabetes. The drug encourages weight loss, and its use has snowballed since its launch as Ozempic for diabetes in 2017. The drug was also approved for weight management, branded as Wegovy, and released in 2021.

The researchers analyzed the records of more than 17,000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analyzed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

There are several limitations to the study. Mass Eye and Ear sees an unusually high number of people with rare eye diseases, the study population is majority white, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. The researchers also couldn’t determine if the patients actually took their medication or if they started and then stopped taking semaglutide at some point and how this might have impacted their risk.  

Importantly, the study does not prove causality, and the researchers don’t know why or how this association exists, and why there was a difference reported in diabetic and overweight groups.

“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is preexisting significant visual loss from other causes.”

Authorship: In addition to Rizzo and Zekavat, other Mass General Brigham co-authors include Jimena Tatiana Hathaway, MD, MPH (MEE); Madhura P. Shah, BS (MEE); David B. Hathaway, MD (BWH); Drenushe Krasniqi, BA (MEE); John W. Gittinger Jr, MD (MEE); Dean Cestari, MD (MEE); Robert Mallery, MD (MEE); Bardia Abbasi, MD (MEE); Marc Bouffard, MD (MEE); Bart K. Chwalisz, MD (MEE) and Tais Estrela, MD (MEE).

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New study confirms forever chemicals are absorbed through human skin

New research, published in Environment International proves for the first time that a wide range of PFAS (perfluoroalkyl substances) – chemicals which do not break down in nature – can permeate the skin barrier and reach the body’s bloodstream.

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A study of 17 commonly used synthetic ‘forever chemicals’ has shown that these toxic substances can readily be absorbed through human skin. 

New research, published in Environment International proves for the first time that a wide range of PFAS (perfluoroalkyl substances) – chemicals which do not break down in nature – can permeate the skin barrier and reach the body’s bloodstream.  

PFAS are used widely in industries and consumer products from school uniforms to personal care products because of their water and stain repellent properties. While some substances have been banned by government regulation, others are still widely used and their toxic effects have not yet been fully investigated. 

PFAS are already known to enter the body through other routes, for example being breathed in or ingested via food or drinking water, and they are known to cause adverse health effects such as a lowered immune response to vaccination, impaired liver function and decreased birth weight.  

It has commonly been thought that PFAS are unable to breach the skin barrier, although recent studies have shown links between the use of personal care products and PFAS concentrations in human blood and breast milk.  The new study is the most comprehensive assessment yet undertaken of the absorption of PFAS into human skin and confirms that most of them can enter the body via this route. 

Lead author of the study, Dr Oddný Ragnarsdóttir carried out the research while studying for her PhD at the University of Birmingham. She explained: “The ability of these chemicals to be absorbed through skin has previously been dismissed because the molecules are ionised. The electrical charge that gives them the ability to repel water and stains was thought to also make them incapable of crossing the skin membrane. 

“Our research shows that this theory does not always hold true and that, in fact, uptake through the skin could be a significant source of exposure to these harmful chemicals.” 

The researchers investigated 17 different PFAS. The compounds selected were among those most widely used, and most widely studied for their toxic effects and other ways through which humans might be exposed to them. Most significantly, they correspond to chemicals regulated by the EU’s Drinking Water Directive.   

In their experiments the team used 3D human skin equivalent models – multilayered laboratory grown tissues that mimic the properties of normal human skin, meaning the study could be carried out without using any animals. They applied samples of each chemical to measure what proportions were absorbed, unabsorbed, or retained within the models. 

Of the 17 PFAS tested, the team found 15 substances showed substantial dermal absorption – at least 5% of the exposure dose. At the exposure doses examined, absorption into the bloodstream of the most regulated PFAS (perfluoro octanoic acid (PFOA)) was 13.5% with a further 38% of the applied dose retained within the skin for potential longer-term uptake into the circulation.  

The amount absorbed seemed to correlate with the length of the carbon chain within the molecule. Substances with longer carbon chains showed lower levels of absorption, while compounds with shorter chains that were introduced to replace longer carbon chain PFAS like PFOA, were more easily absorbed. Absorption of perfluoro pentanoic acid for example was four times that of PFOA at 59%. 

Study co-author, Dr Mohamed Abdallah, said “our study provides first insight into significance of the dermal route as pathway of exposure to a wide range of forever chemicals.  Given the large number of existing PFAS, it is important that future studies aim to assess the risk of broad ranges of these toxic chemicals, rather than focusing on one chemical at a time.”  

Study co-author, Professor Stuart Harrad, of the University of Birmingham’s School of Geography, Earth and Environmental Sciences, added: “This study helps us to understand how important exposure to these chemicals via the skin might be and also which chemical structures might be most easily absorbed. This is important because we see a shift in industry towards chemicals with shorter chain lengths because these are believed to be less toxic – however the trade-off might be that we absorb more of them, so we need to know more about the risks involved.” 

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Chronic loneliness may increase stroke risk among older adults

When loneliness was assessed at baseline only, the participants considered lonely had a 25% higher risk of stroke than those not considered lonely. Among the participants who reported loneliness at two time points, those in the “consistently high” group had a 56% higher risk of stroke than those in the “consistently low” group, even after accounting for a broad range of other known risk factors.

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Chronic loneliness may significantly raise older adults’ risk of stroke, according to a new study led by Harvard T.H. Chan School of Public Health. 

“Loneliness is increasingly considered a major public health issue. Our findings further highlight why that is,” said lead author Yenee Soh, research associate in the Department of Social and Behavioral Sciences. “Especially when experienced chronically, our study suggests loneliness may play an important role in stroke incidence, which is already one of the leading causes of long-term disability and mortality worldwide.”

While previous research has linked loneliness to higher risk of developing cardiovascular diseases, few have examined the impact on stroke risk specifically. This study is one of the first to examine the association between loneliness changes and stroke risk over time.

Using 2006-2018 data from the Health and Retirement Study (HRS), the researchers assessed the association between changes in loneliness and stroke incidence over time. During 2006-2008, 12,161 participants—all adults ages 50 and above who never had a stroke—responded to questions on the Revised UCLA Loneliness Scale, from which the researchers created summary loneliness scores. Four years later (2010-2012), 8,936 participants who remained in the study responded to the same questions again. The researchers then placed the participants into one of four groups according to their loneliness scores across the two time points: “consistently low” (those who scored low on the loneliness scale at both baseline and follow-up); “remitting” (those who scored high at baseline and low at follow-up); “recent onset” (those who scored low at baseline and high at follow-up); and “consistently high” (those who scored high at both baseline and follow-up).

Among the participants whose loneliness was measured at baseline only, 1,237 strokes occurred during the follow-up period (2006-2018). Among the participants who provided two assessments of loneliness over time, 601 strokes occurred during the follow-up period (2010-2018). The researchers analyzed each group’s risk of stroke over the follow-up period in the context of their experiences with loneliness, controlling for other health and behavioral risk factors. These included social isolation and depressive symptoms, which are closely related but distinct from loneliness.

The findings showed a link between loneliness and higher risk of stroke and found that chronic loneliness heightened risk the most. When loneliness was assessed at baseline only, the participants considered lonely had a 25% higher risk of stroke than those not considered lonely. Among the participants who reported loneliness at two time points, those in the “consistently high” group had a 56% higher risk of stroke than those in the “consistently low” group, even after accounting for a broad range of other known risk factors. While the baseline analyses suggest loneliness at one time point was associated with higher risk, those who experienced remitting or recent onset loneliness did not show a clear pattern of increased risk of stroke—suggesting that loneliness’ impact on stroke risk occurs over the longer term.

“Repeat assessments of loneliness may help identify those who are chronically lonely and are therefore at a higher risk for stroke. If we fail to address their feelings of loneliness, on a micro and macro scale, there could be profound health consequences,” said Soh. “Importantly, these interventions must specifically target loneliness, which is a subjective perception and should not be conflated with social isolation.”

The authors noted that further research examining both nuanced changes in loneliness over the short-term, as well as loneliness patterns over a longer period of time, may help shed additional light on the loneliness-stroke association. They also noted that more research is needed to understand the potential underlying mechanisms, and that the study findings were limited to middle-aged and older adults and may not be generalizable to younger individuals.

Other Harvard Chan authors included Ichiro Kawachi, Laura Kubzansky, Lisa Berkman, and Henning Tiemeier.

Chronic Loneliness and the Risk of Incident Stroke in Middle and Late Adulthood: A Longitudinal Cohort Study of U.S. Older Adults” was written by Yenee Soh, Ichiro Kawachi, Laura D. Kubzansky, Lisa F. Berkman, Henning Tiemeier, and appeared in eClinicalMedicine.

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