Wellness
Women have a far higher risk of dementia – and urgent action is needed
Recently published research has turned an overdue spotlight on the disproportionate burden of dementia borne by women. It is encouraging to see this research progressing, and inspiring to see it stimulating public awareness and discussion of a disparity that has too long been overlooked: women are twice as likely as men to develop Alzheimer’s disease.
By Andrea Pfeifer
We have been searching for new treatments for Alzheimer’s disease for decades and are now able to offer patients medicines that can slow the rate of memory loss. The research that led to the approval of these effective new medicines created a tremendous bank of knowledge about how Alzheimer’s causes damage to the brain – knowledge that enables us now, for the first time, to work on strategies to prevent damage before it happens.
As much as we have learned, however, we still do not understand why women are more prone to developing dementia and Alzheimer’s than men, nor do we know whether or how approaches to diagnosis, treatment and prevention should differ based on sex.
Researchers around the world are urgently studying questions about what causes these differences, and what they mean for treatment and prevention. In addition, new and exciting research is investigating sex-based differences in the effects of lifestyle and environmental factors that could lead to precision prevention approaches tailored for women and for men.
For this research to continue, its crucial to support public health strategies – and for us to continue to talk about dementia risk with the women in our lives to raise awareness of the ways we already have to preserve brain health.
Factors at play
Worldwide, about two-thirds of people living with Alzheimer’s are women. Women face a disproportionate burden in terms of care and lost economic productivity, and this is true across high-, middle- and lower-income countries.
Multiple reasons have been suggested to explain this difference. Among the hypotheses are higher life expectancy in women, because age is a risk factor for Alzheimer’s, and lower education in women, because limited education also is a risk factor. Geographical differences have been found, and we also know that one of the genetic factors that increases the risk of Alzheimer’s, a gene variant called APOE e4, has a stronger effect in women.
Women who carry APOE e4 are more likely than male carriers to accumulate toxic proteins in the brain, called amyloid plaques and tau tangles, which drive the loss of memory and cognition in Alzheimer’s. In addition, women who have amyloid and tau accumulation have faster disease progression rates compared with men.
Hormonal changes, particularly the decline in oestrogen during menopause, also may contribute to increased Alzheimer’s risk in women. But all women experience menopause, and not all women develop Alzheimer’s, so researchers are still working to understand how and why changes in hormones affect Alzheimer’s risk.
A study recently published in Science Advances by a team at Massachusetts General Hospital led by Dr. Gillian Coughlan investigated associations between hormone therapy and tau accumulation in menopausal women. The results further support a role for hormones in Alzheimer’s, and also highlighted a highly complex relationship between hormones and other factors such as age that need continued study.
Environmental and lifestyle factors also play a role in Alzheimer’s risk, and we are just beginning to study whether there are sex-based differences here as well.
All of these factors need more study, and understanding how they combine to affect risk for women as a group and for men and women as individuals will take time. Fortunately, there is a clear path forward.
Charting a way forward
The balance between women and men in clinical trials for Alzheimer’s treatments, which have historically underrepresented women, have improved in recent years. Yet detailed analyses of sex-specific differences in these studies are still lacking.
For example, trials of both the new Alzheimer’s medicines showed some difference in treatment results for women vs. men. However, neither trial was designed to draw conclusions about how important or meaningful those differences are, or to understand whether such differences could be related to other factors such as hormone profiles, education, and so on.
Going forward, we need to ensure that the participation of women and men in clinical trials reflects the prevalence of Alzheimer’s in both sexes. There is a need for sex-based data collection and analysis across all stages of research, from basic biology research to clinical trials.
One way to ensure this is to make the integration of sex and gender in research plans a requirement for funding or publishing. Another is to enhance diversity in teams in research, policy, and healthcare practice.
We also need to redouble our efforts to reduce dementia risk globally, and to increase awareness of the tools that we already know can make a difference.
My goal, as the CEO of a biotech working in Alzheimer’s disease and the co-founder and Chair of the Global BHP Braintrust, is to develop and promote effective strategies to reduce the overall risk of dementia using a Precision Prevention approach that includes active immunotherapy and lifestyle changes.
Active immunotherapy is a type of medicine that stimulates the immune system to clear or prevent the accumulation of pathological proteins like amyloid or tau. These medicines are still in development but could be available in as little as five years.
Lifestyle interventions enable everyone to target modifiable risk factors such as diet, exercise, cognitive and social stimulation, and vascular health.
It is estimated that at least 40 per cent of cases worldwide can be linked to modifiable facets of lifestyle including cardiovascular, metabolic and environmental factors. A landmark study called the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed that a multi-faceted lifestyle intervention program could improve brain health and prevent cognitive decline by about 30 per cent.
The intervention combined healthy food, physical activity, mental stimulation, social activities, and cardiovascular risk monitoring.
The benefit of the intervention on cognitive outcomes did not differ significantly between men and women. Sex-specific differences in certain cognitive domains, as well as in the adoption of lifestyle changes, point to the opportunity to further improve the impact of the intervention.
The Global BHP BrainTrust is now collaborating on FINGERS Plus for Women, a research initiative to explore the potential for gender-specific interventions to further reduce the risk of dementia.
A better future
Used together, both active immunotherapy and lifestyle interventions could enable a more personalized risk reduction strategy based on an individual’s sex, genetic risk, biomarkers, and lifestyle factors.
Many of us have family or friends who suffer from dementia. We know that it is a global scourge that silently ravages millions of lives.
Together with other researchers, companies, and policymakers, we have the capacity to close the gap between women and men, addressing this pressing public health concern for all.
Prof. Andrea Pfeifer is co-Founder and CEO of AC Immune, a Swiss biopharmaceutical company pioneering precision prevention for neurodegenerative diseases. She has led the company since founding in 2003 and through an IPO and multiple partnerships with leading pharmaceutical companies. She was previously Head of Nestlé Research Centre, where she played a major role in connecting science and business.
Prof. Pfeifer is a key member of the CEOi initiative on Alzheimer’s Disease and the Davos Alzheimer’s Collaborative (DAC), a Founding Chair of the Global BHP Braintrust, and in 2021 was awarded the first SEF.WomenAward for CEO of the Year by the Swiss Economic Forum. She holds a Ph.D. in Toxicology (Cancer Research) from the University of Würzburg, Germany and is an Honorary Professor at the Ecole Polytechnique Fédérale de Lausanne (EPFL).
Light exercise and less sitting may reduce pregnant women’s risk of serious blood pressure complications, according to a new study.
Researchers have proposed a daily activity and sleep guide that they say was linked to a nearly 30 per cent lower risk of hypertensive disorders of pregnancy.
The suggested pattern includes fewer than eight hours of sedentary time, at least seven hours of light physical activity, around 22 minutes of more intense activity and nearly nine hours of sleep.
The University of Iowa-led study examined the daily behaviours of 470 pregnant women across all stages of pregnancy.
Participants wore monitors that measured physical activity over 24-hour periods and recorded how long they spent asleep.
Hypertensive disorders of pregnancy include chronic high blood pressure, gestational hypertension and pre-eclampsia.
Gestational hypertension is high blood pressure that develops during pregnancy, while pre-eclampsia is a potentially serious condition involving high blood pressure and signs that organs may be affected.
Sedentary behaviour means being mostly inactive, such as sitting or lying down.
Light physical activity can include casual walking, moving around the home or standing.
Moderate to vigorous activity includes movement such as brisk walking, where breathing and heart rate increase.
Kara Whitaker, associate professor in the department of health, sport, and human physiology at Iowa and corresponding author of the study, said: “We are identifying the optimal composition of movement behaviours across the day associated with the lowest risk of developing HDP and the most improved health outcomes.
“This blueprint holds for each and every trimester of pregnancy.”
Study participants were enrolled at sites in Iowa City, Pittsburgh and Morgantown, West Virginia.
The women wore activity and sleep monitors for at least one week during each trimester of pregnancy.
Four in five participants were non-Hispanic white and nearly a quarter lived in rural areas.
The data showed a steep rise in risk among pregnant women who were sedentary for more than 10 hours a day.
Women who increased light physical activity to at least four hours a day reduced their risk of hypertensive disorders of pregnancy to 15 per cent from 30 per cent.
Whitaker said: “Just moving around more seems to have significant health benefits.
“And I think it also may be a more feasible target for women who are pregnant who are not exercising regularly.”
The researchers said they were surprised that longer durations of moderate to vigorous physical activity did not appear to provide additional benefit.
Sleep beyond a certain duration also did not appear to bring major further benefits.
Whitaker said: “Through this study, we are providing evidence that reducing sedentary behaviour and engaging in light physical activity are important, and maybe more important, when it comes to pregnancy and health.”
The findings may be relevant beyond pregnancy because clinical research has shown that women who develop hypertensive disorders of pregnancy are more than twice as likely to develop heart disease later in life.
Cardiovascular disease includes conditions affecting the heart and blood vessels, such as heart disease and stroke.
Whitaker said: “We know that cardiovascular disease is the number one killer of women, and if we can intervene in pregnancy and prevent women from developing a hypertensive disorder of pregnancy, we are putting them on a better trajectory, away from cardiovascular disease and toward more optimal cardiovascular health.”
The study was published online on June 10.
A second study, published online on May 27, looked more closely at the ratio and type of sedentary behaviour and light physical activity linked to a lower risk of hypertensive disorders of pregnancy.
Whitaker is a lead co-author on that study.
Co-authors in the June 10 study include Alex Crisp, Jaemyung Kim, Karina Smith, Donna Santillan, Mark Santillan and Bridget Zimmerman, from Iowa; Jacob Gallagher, from Iowa State University; Melissa Jones, from Oakland University in Michigan; Bethany Barone Gibbs, Katrina Wilhite, Alexis Thrower and Iqra Sheikh, from West Virginia University; and Sabera Rahman, Janet Catov, Christopher Kline and Maisa Feghali, from the University of Pittsburgh.
The National Institutes of Health, the University of Iowa Institute for Clinical and Translational Science, the University of Pittsburgh Clinical and Translational Science Institute and the West Virginia Clinical and Translational Science Institute funded the research.
Pregnant women’s expectations about postpartum sleep may predict sleep quality after birth, outweighing prior sleep and psychiatric history, a study suggests.
The findings suggest attitudes and beliefs about sleep during pregnancy could be a modifiable risk factor for postpartum sleep concerns.
They also indicate that, among women expecting the poorest sleep, higher postpartum anxiety may further worsen sleep quality.
Sammy Dhaliwal, lead author is clinical health psychologist and research fellow in the department of obstetrics and gynaecology at the Perelman School of Medicine at the University of Pennsylvania.
Dhaliwal said: “Most pregnant women in our sample anticipated poor postpartum sleep before it occurred, and it was striking that those expectations predicted worse sleep outcomes even after accounting for factors such as prior sleep disorders, psychiatric history, and number of previous births.
“This suggests that attitudes and beliefs about sleep during pregnancy may represent a modifiable target for early intervention before postpartum sleep problems emerge.”
Sleep disturbance affects an estimated 60 to 80 per cent of postpartum women and is linked to a higher risk of depression and anxiety.
Researchers said it is often regarded as an expected part of life after childbirth rather than a health issue that may be addressed earlier.
The study enrolled 432 pregnant women at about 24 weeks of gestation, meaning around 24 weeks into pregnancy.
Participants completed measures of their expectations about postpartum sleep, current sleep quality using the Pittsburgh Sleep Quality Index, and mood using validated depression and anxiety scales.
Assessments were repeated at six, 12 and 24 weeks postpartum.
A subset of 49 women also wore wrist actigraphy devices at six to eight weeks postpartum.
Actigraphy uses a wearable device, similar to a watch, to estimate sleep and wake patterns based on movement.
The results showed that 70 per cent of pregnant women, or 301 of 432 participants, expected poor sleep in the postpartum period.
Researchers found that predicted sleep disruption during pregnancy was a significant predictor of postpartum sleep concerns.
Among first-time pregnant women without prior health concerns, those who expected greater sleep disturbance had significantly more disrupted sleep after birth, measured by both actigraphy and self-report.
Among women who expected the worst sleep quality, higher postpartum anxiety significantly worsened both measured sleep and self-reported sleep, independent of anxiety levels during pregnancy.
Dhaliwal said the findings point to two possible areas for intervention: addressing sleep-related beliefs during pregnancy and treating postpartum anxiety.
Dhaliwal said: “Postpartum sleep disruption is often treated only after problems develop, but our findings suggest there may be an opportunity to intervene earlier during pregnancy.
“Addressing sleep-related beliefs and postpartum anxiety during prenatal and postpartum care may help improve sleep and emotional well-being in new mothers.”
A four-week Pilates programme may improve heart, metabolic and stress measures in previously sedentary women, a small study suggests.
Pilates is a mind-body form of exercise that has been linked to better fitness, balance, posture, muscular endurance, mental wellbeing and quality of life in different groups.
Built around breathing, concentration, control, precision, centring and flow, Pilates is already used in physiotherapy, rehabilitation and preventive health. The new study looked at whether a structured four-week programme could affect cardiovascular, metabolic, body and stress-related measures in sedentary adult women.
The longitudinal study included 30 sedentary women split into two age groups, 30 to 40 and 50 to 60.
All participants completed a standardised, supervised Pilates programme lasting four weeks, with three sessions a week lasting 50 to 60 minutes.
Researchers measured resting heart rate, systolic and diastolic blood pressure, body mass index, abdominal circumference, fasting blood glucose and serum cortisol at the start and end of the programme.
Systolic and diastolic blood pressure are the top and bottom readings in a blood pressure test. Cortisol is a hormone linked to the body’s stress response.
The four-week Pilates programme was linked to improvements in cardiovascular, metabolic, body and neuroendocrine measures, although not every change reached statistical significance within each age group.
In the younger group, significant reductions were seen in heart rate, blood pressure, body mass index and fasting blood glucose after the intervention.
The reduction in blood pressure after the programme was significantly greater in the older group than in the younger group.
Older participants also showed a greater reduction in glucose and cortisol levels after the intervention than younger participants.
Analysis also found significant links between cardiovascular, metabolic and neuroendocrine changes.
In the younger group, this was particularly seen between heart rate and blood pressure responses.
In the older group, it was particularly seen between changes in body mass index and fasting glucose.
The findings suggest Pilates could be a useful multidimensional exercise approach for cardiometabolic health and stress regulation in previously sedentary women.
The researchers said the larger reduction in blood pressure seen in the older group may reflect a higher cardiometabolic burden at the start, leaving more room for improvement after the programme.
The greater reduction in fasting glucose and cortisol in older participants may similarly suggest that people with higher baseline metabolic and neuroendocrine dysfunction could benefit more from structured exercise such as Pilates.
Although Pilates is known to improve body composition through energy use, neuromuscular activation and support for healthier habits, the researchers said the fall in body mass index over four weeks is unlikely to be explained by Pilates alone.
They noted that participants were also told to avoid alcohol, sugar-containing products and sugar-sweetened drinks during the intervention, which may have contributed to the change.
In the younger group, the link between heart rate and blood pressure suggested coordinated cardiovascular responses after Pilates.
The researchers also found that cortisol appeared to be linked to blood pressure and body mass index, suggesting stress-related changes may be tied to cardiovascular and body regulation after the intervention.
In the older group, the link between body mass index and fasting glucose highlighted the relationship between body fat and metabolic regulation.
A positive link between blood pressure and body mass index in this group also suggested that improvements in vascular regulation may be associated with reductions in body mass.
Overall, the findings suggest Pilates-related physiological changes may involve interconnected cardiovascular, body, metabolic and neuroendocrine mechanisms, with different response patterns by age.
The study has important limits. It did not include a non-exercise control group, so it cannot prove Pilates directly caused the changes.
The sample size was also small, which limits how far the findings can be applied more widely.
The authors also noted that cortisol was measured using a single fasting morning sample, which limits conclusions about broader hypothalamic-pituitary-adrenal axis regulation, the system involved in the body’s stress response.
They said larger studies with longer follow-up will be needed to confirm whether Pilates causes these physiological changes over time.
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