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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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Maintaining a healthy heart may require regular doses of positivity

The findings of this study further point to the importance of attending to mental and behavioral health for cardiovascular disease prevention and cardiovascular health optimization.

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Positive psychology interventions such as mindfulness, gratitude journaling and optimism training can consistently improve blood pressure, inflammation markers and other cardiovascular disease risk factors within a matter of weeks, a recent study found. However, since these benefits are associated with lifestyle changes such as eating healthier and greater physical activity, the researchers suggested that ongoing reinforcements may be needed to stay on course long term.

Rosalba (Rose) Hernandez, a professor of social work at the University of Illinois Urbana-Champaign, led a team that analyzed the findings of 18 randomized controlled trials that used positive psychological and mindfulness interventions to enhance mental or physical health.

The programs that the team reviewed included individual methods — such as structured telephone sessions, journaling with brief check-ins and digital platforms such as apps and text messaging — and interactive in-person group sessions, as well as hybrid formats that blended these with online tools and virtual meetings. Most of the programs consisted of weekly sessions and at-home activities that reinforced the skills taught, with the majority of programs lasting from six to 12 weeks, the team found.

In general, the programs included 50-200 adults with elevated cardiovascular risk factors such as uncontrolled hypertension, heart failure or other conditions. Typically, the participants were in their late 50s to mid-60s, and women comprised 35-55% of the samples across those studies that reported their participants’ gender, according to the researchers.

“In hypertension and postacute coronary syndrome cohorts, mindfulness-based programs delivered over an eight-week period reduced systolic blood pressure and lowered inflammatory markers such as high-sensitivity C-reactive protein and fibrinogen,” said Hernandez, who is a Fellow of the American Heart Association. “A 12-week spirituality-based digital intervention achieved one of the largest reductions — reducing systolic blood pressure measured with a standard cuff by 7.6 points, and central systolic pressure — which is measured in the aorta as it leaves the heart — by 4.1 points.”

In prior research on positive psychology interventions, scientists seldom defined the dose that was needed to obtain the beneficial effects, Hernandez said. She and the team members sought to clarify the frequency and duration that was most likely to improve individuals’ cardiovascular health.

Programs that had more frequent contact with their participants yielded the most consistent physiological benefits, underscoring the opportunity to embed positive psychological strategies into long-term cardiovascular care, Hernandez said.

The team found that the strongest behavioral improvements were achieved by an eight-week program delivered over WhatsApp that combined weekly sessions with daily microtasks, motivating participants to engage in greater physical activity, eat a healthier diet and take their medication as prescribed. A program that included motivational interviewing succeeded in increasing cardiac patients’ levels of physical activity by 1,800 steps a day and their medication adherence, while the mindfulness programs improved participants’ activity levels and diets only, according to the study.

“The therapeutic dose that was most consistently linked with improvements in blood pressure, inflammation and endothelial function was daily practice reinforced by weekly sessions over eight to 12-week periods,” Hernandez said. “Therapeutic dosing typically involved high-frequency dosing over this time period to obtain short-term physiologic benefits, while ongoing less-intensive contact may be needed to sustain behavioral change.”

Published in the journal Cardiology Clinics, the study was co-written by University of South Florida social work professor Soonhyung Kwon; Alyssa M. Vela, a professor of surgery and of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine; and Katharine S. Edwards, a professor of cardiovascular medicine and of psychiatry and behavioral medicine at Stanford Medicine.

“The findings of this study further point to the importance of attending to mental and behavioral health for cardiovascular disease prevention and cardiovascular health optimization,” Vela said. “This speaks to the need for routine screening and integration of cardiac behavioral medicine to allow for access to important interventions.”

The current study adds to a growing body of research linking psychological well-being — including traits such as optimism, positive affect and gratitude — with cardioprotective benefits.

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Heart disease risk may start in the womb, study finds

Young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.

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A child’s future heart health may be partially shaped before they are born, reports a new Northwestern Medicine study that found pregnancy complications are linked to poorer cardiovascular health in offspring more than 20 years later.

The study found that young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.

The authors said the study adds to growing evidence that cardiovascular risk may be transmitted across generations through a combination of biological, environmental and behavioral factors.

“That means we must make sure people maintain good health from childhood into young adulthood, so that if or when someone becomes a parent, they pass on the best opportunity for good health to their children,” said study senior author Dr. Nilay Shah, assistant professor of medicine in the division of cardiology at Northwestern University Feinberg School of Medicine.

How the study was conducted

Shah and colleagues evaluated nearly 1,350 mother-child pairs from the Future of Families and Child Well-Being Study, which enrolled mothers and children at birth between 1998 and 2000 across 20 U.S. cities. The children were then followed into adulthood.

Using delivery hospitalization records, the Northwestern scientists first identified whether mothers experienced pregnancy complications, including high blood pressure during pregnancy, gestational diabetes (high blood sugar during pregnancy) or preterm birth (before 37 weeks of pregnancy).

The three pregnancy complications are on the rise, and affect almost one in four pregnancies in the U.S.

The research team then analyzed cardiovascular health of offspring at age 22, using blood pressure measurements, blood testing, body mass index assessments and carotid artery ultrasounds to look for signs of artery injury.

Finally, the scientists compared participants with and without exposure to each pregnancy complication and adjusted for factors like income, education, difference in birth weight and smoking during pregnancy.

Key findings

At around age 22, participants whose mothers had high blood pressure during pregnancy had:

  • Higher body mass index (+2.8 BMI points)
  • Higher diastolic blood pressure (+2.3 mm Hg)
  • Higher blood sugar levels (+0.2% HbA1c)
  • Thicker artery walls (~0.02 mm)

While the difference in artery wall thickness may seem small, the study authors said it corresponds to roughly three to five years of additional vascular aging. That means arteries looked older and less healthy than expected, which raises the risk of future heart disease.

Other pregnancy complications also showed some long-term effect:

  • Exposure to gestational diabetes was linked to worse blood pressure and some evidence of artery thickening
  • Being born preterm was associated with higher blood sugar levels

‘Most heart disease is preventable’

With pregnancy complications on the rise in the U.S., Shah said the study provides compelling evidence that improving health before and during pregnancy could help reduce heart disease risk in the next generation.

“There is evidence that both parents’ health at the time of conception and during pregnancy influences a child’s health,” he said. “So, promoting health from an early age, like exercising regularly, eating healthfully, never smoking and getting enough sleep, is not just meant for an individual, but doing so may help future generations be healthier, too.”

Shah also emphasizes that risk is not destiny.

“The good news is that most heart disease is preventable,” he said. “If you experienced high blood pressure or high blood sugar during pregnancy, or your child was born early, it does not absolutely mean that your child will have worse health as adults. But I would encourage you to pay attention now to your child’s health behaviors.

“What children learn in childhood sets the stage for their health across their lives. If you are wondering whether your children’s behaviors are healthy, or are considering making a change, please speak with your child’s pediatrician for advice and guidance.”

Other Northwestern co-authors include Emily Lam, Abigail Gauen, Dr. Sadiya Khan, Alexa Freedman and Norrina Allen.

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Viagra could hold key to halting Peyronie’s disease

Combining two widely prescribed drug classes could provide the first effective treatment for early-stage Peyronie’s disease.

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Combining two widely prescribed drug classes could provide the first effective treatment for early-stage Peyronie’s disease, according to a study published in The Journal of Sexual Medicine.

Peyronie’s disease (PD) is caused by the development of fibrotic scar tissue within the penis, leading to pain, curvature, sexual dysfunction and, in many cases, significant psychological distress. It affects an estimated 10 per cent of men during their lifetime, but despite its prevalence, treatment options are limited, particularly in the early phase of the condition.

The study, carried out by Anglia Ruskin University (ARU) and University College London Hospital (UCLH), found that combining phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil (Viagra) and tadalafil (Cialis) with selective oestrogen receptor modulators (SERMs), including tamoxifen, may slow or even stop disease progression when given early.

The clinical study, carried out by Professor David Ralph of UCLH, evaluated outcomes in 133 men diagnosed with acute Peyronie’s disease who were treated with the drug combination for three months. Their results were compared with a smaller group of patients receiving standard care, which included giving vitamin E or no treatment at all. Standard care did not include surgery.

The study found 43 per cent of patients on the combination experienced an improvement in penile curvature, almost three times higher than in the standard‑care group (15 per cent).

At the start of treatment, 65 per cent of patients in the combination group reported pain during erections. After three months, that figure had fallen to just 1.5 per cent. By comparison, pain prevalence in the standard‑care group fell from 50 per cent to 27 per cent.

The clinical findings build on earlier laboratory work led by Professor Selim Cellek at ARU’s Fibrosis Research Group. Over the course of several years, Professor Cellek’s team screened 1,953 FDA‑approved drugs to identify compounds capable of blocking the transformation of fibroblasts into myofibroblasts, the key cells responsible for fibrosis. PDE5 inhibitors and SERMs emerged as particularly effective, and when used together demonstrated an effect greater than either drug alone.

Currently, there are no approved oral therapies proven to prevent early disease progression, forcing patients in the acute phase to wait until the condition stabilises before they can be offered treatments including injections or surgery.

Professor Cellek said: “Positive findings from this pilot clinical study validate our drug‑screening approach in the lab. It shows how repurposing well‑known medicines can accelerate progress in areas of unmet clinical need.

“Because both PDE5 inhibitors and SERMs are already widely used in clinical practice and have established safety profiles, the approach could be readily adoptable if confirmed in larger studies.

“These results suggest that early intervention targeting fibrosis could change how we treat Peyronie’s disease. Repurposing existing drugs may allow us to move from managing symptoms to modifying the disease itself.”

Professor David Ralph, Professor of Urology at UCLH, said: “This paper confirms the basic science research with regards to halting the progression of Peyronie’s disease. In previous papers we have noted that tamoxifen and PDE5 inhibitors inhibit the transformation of fibroblasts into myofibroblasts and therefore contraction of the plaque.

“This has now been put into clinical practice where this paper shows that when tamoxifen and a PDE5 inhibitor are combined, there is statistically less progression of the disease and improvement in curvature compared to the control arm. This is where from bench to clinical practice prevails and hopefully now a prospective clinical trial can be initiated.”

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