Estrogen-based menopausal hormone therapy = lower Alzheimer’s risk

 Women on regimens of estrogen-only menopausal hormone therapy are at reduced risk of Alzheimer’s disease, a study by Stanford Medicine investigators has found.

Because estrogen-only therapy is generally prescribed for women without a uterus, most of these users presumably had had hysterectomies.

The study, published Aug. 12 in Neurology, is the first to measure the connection between menopausal hormone therapy, or MHT, and reductions in Alzheimer’s-related pathological deposits in autopsied brains. 

Alzheimer’s disease is, by far, the leading cause of dementia in older people. About two-thirds of Alzheimer’s patients are women. Earlier studies have indicated that menopausal hormone therapy raises dementia risk. But the new study suggests otherwise.

“Our study is unique in that we looked at all the standards of Alzheimer’s diagnosis, including the gold-standard outcome: Alzheimer’s-associated hallmarks in autopsied brains,” said Hadi Hosseini, PhD, an associate professor of psychiatry and behavioral sciences who is the study’s senior author. “No one has previously looked at substantial numbers of postmortem Alzheimer’s disease outcomes.”

Jennifer Bruno, PhD, an instructor in psychiatry and behavioral sciences, and former postdoctoral scholar Jacob Shaw, PhD, share lead co-authorship.

“Many conditions impact memory. Clinical diagnoses are often not accurate," Hosseini said. “Although there’s been great progress with bloodborne and cerebrospinal fluid biomarkers, they don’t tell you the amount and precise location of the brain damage. By looking where the actual damage is done — the brain — you can see where the Alzheimer’s-associated defining features are and how many of them are there.”

Evidence from analysis of living participants’ cerebrospinal fluid and blood samples supported the study’s autopsy findings. Estrogen-only menopausal hormone therapy users had 39% lower odds than non-users of receiving a clinical diagnosis of dementia during their lifetimes, and they performed better on memory tests and in their overall ability to function independently. 

The researchers explored two existing databases, numbering 21,462 participants in all, for data on deceased female participants whose brains were autopsied for the presence of two defining pathological features of Alzheimer’s disease: so-called amyloid plaques and neurofibrillary tangles. 

Analyzing results from 258 brain autopsies of women who had reported using menopausal hormone therapy in an estrogen-only formulation, the scientists compared the levels and locations of these two Alzheimer’s hallmarks, along with a third one — the density of individual amyloid plaques — with those in the brains of some 2,701 women who had reported no use of any form of menopausal hormone therapy, and assigned scores to the result.

They found that estrogen-only MHT use was associated with a statistically significant decrease in the presence of these defining Alzheimer’s hallmarks. 

Using a measure known as the odds ratio, the Stanford Medicine team reported a 35% reduction in the odds of a woman’s developing Alzheimer’s disease among estrogen-only menopausal hormone therapy users.

“MHT appears to exert a modest but meaningful and statistically significant protective effect on the risk of developing Alzheimer’s pathology,” Bruno said. “While this is by no means more powerful than such very well-known factors as age, possession of the genetic variant knowns as APOE4 or a history of hypertension, it’s nonetheless quite a consistent effect, spanning multiple Alzheimer’s-related outcomes.” 

The Stanford Medicine study adjusted for these factors, as well as for education and race. The finding of a cognitive benefit for estrogen-only menopausal hormone therapy users carries direct implications for about one-third of all women of menopausal age. By age 60, more than 30% of women have had hysterectomies and no longer have a uterus. Estrogen-only treatment is specifically recommended for these women.

The women in the study skewed older (their average age was 70), and many had had hysterectomies. So, most of them were on estrogen-only regimens. The researchers couldn’t obtain conclusive autopsy findings for dementia risk of women on estrogen-plus-progestin formulations, because the number of autopsied women on such formulations was too small to reach a conclusion about its effect. 

In addition, topical estrogen-only users rather than those on oral estrogen therapy were not counted. 

As a result, the findings are applicable only to estrogen-only formulation, not to estrogen-plus-progestin formulation and not to topical as opposed to oral estrogen administration. And while the association with reduced Alzheimer’s risk is clear, it still doesn’t amount to definitive proof of causality.

“There have been a lot of conflicting findings about MHT’s effects on Alzheimer’s disease outcomes.” Hosseini said. “Different studies may have involved different age ranges of initiating MHT. They may have focused on varying clinical outcomes, used divergent biomarkers or lumped together different MHT formulations, or studied different routes of administration or different durations of use. Some of those studies may not have adequately corrected for various genetic, cardiovascular or other risk factors.”

“Assessments of ‘cognitive decline’ are necessarily somewhat subjective,” Bruno concurred, noting that such declines may depend on who is doing the assessment and may result from any number of different physiological causes ranging from a severe stroke to a bad night’s sleep. 

Early studies suggested that menopausal hormone therapy might be useful for protecting menopausal women from dementia. But other studies that followed yielded inconclusive results. A large analysis published in 2003, the Women’s Health Initiative Memory Study, indicated the opposite effect — estrogen-plus-progestin formulations seemed to increase dementia risk, at least when initiated at an older age. 

The Women’s Health Initiative study also tied the estrogen-plus-progestin combination to increased risk of breast cancer and heart disease. In 2025, the Food and Drug Administration announced the removal of a black-box warning to this effect. But the publicity surrounding the 2003 report had long since sent overall menopausal hormone therapy usage on a roller coaster ride that has yet to be completed. Estimates of women’s use of the therapy during their lifetimes were once close to 27%.

“Now that use estimate has plummeted to below 5%,” Hosseini said. 

“The recent medical literature suggests that MHT is more beneficial when initiated during or soon after menopause,” he said. “The women in our study tended to be older. If anything, our finding underestimated the benefit due to their late initiation of therapy.”

“For a long time,” Bruno said, “the going recommendation was ‘Don’t use MHT for memory decline.’ This study flies in the face of that recommendation.” 

DOI

10.1212/WNL.00000000002184 

Longer meal intervals = faster disease accumulation in older adults

 Older adults who typically had longer intervals between meals accumulated chronic diseases more rapidly over time than those with shorter intervals, according to a study from Karolinska Institutet published in the Journal of Internal Medicine. The association was most pronounced among people aged 78 years and older.

Interest in fasting has increased in recent years, but relatively little is known about how meal timing affects health in older adults. In this new study, researchers investigated whether the duration of the longest daily interval between meals was associated with the accumulation of chronic diseases over time.

The researchers used data from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), which includes 2,981 people in Stockholm who were aged 60 years or older at the start of the study. Participants were followed for up to 15 years. The duration of intervals between meals was estimated from participants’ self-reported information about when they typically ate during a 24-hour period.

Association seen across disease types

Longer intervals between meals were associated with faster accumulation of chronic diseases over time. In particular, people whose longest interval between meals during a typical day was 14 to 24 hours accumulated chronic diseases more rapidly than those whose longest interval was 6 to 11.5 hours. The association was observed for the total number of chronic diseases, as well as for cardiovascular and neuropsychiatric diseases, but not for musculoskeletal diseases.

“Much of the research on fasting has been conducted in younger or middle-aged populations. Our findings suggest that the associations may be different in older adults, particularly among the oldest age groups”, says Adrián Carballo Casla, last author of the study and postdoctoral researcher at the Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

The researchers emphasise that the study cannot determine cause and effect. Although longer intervals between meals were linked to faster disease accumulation, the study cannot establish whether the fasting pattern independently contributed to this outcome.

For information on funding and any potential conflicts of interest, please see the study.

Publication: “Habitual fasting duration and accelerated multimorbidity in older adults”, Luis Kalmbach, David Abbad-Gomez, Giorgi Beridze, Fernando Rodríguez-Artalejo, Davide Liborio Vetrano, Amaia Calderón-Larrañaga, Adrián Carballo-Casla, Journal of Internal Medicine, online August 20, 2026, doi: 10.1111/joim.70150

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Journal

Journal of Internal Medicine

DOI

10.1111/joim.70150

A diet high in antioxidants was linked with a lower risk of cervical cancer in women

 In research published in the International Journal of Gynecology & Obstetrics, a diet high in antioxidants was linked with a lower risk of cervical cancer in women.

In the study, investigators analyzed 2003–2018 data from 1,044 US women participating in the National Health and Examination Survey: 174 with and 870 without cervical cancer. With these data, the team looked for an association between cervical cancer and the Composite Dietary Antioxidant Index (CDAI)—a validated composite score that reflects an individual’s intake level of dietary antioxidants, based on dietary recall interviews.

After adjusting for other factors that might affect cancer risk, the researchers found that each 1-unit increase in the CDAI was associated with a 11.4% lower prevalence of cervical cancer. Participants in the highest CDAI tertile had a 55.8% lower prevalence of cervical cancer than those in the lowest tertile. Additional analyses indicated a linear inverse association between the CDAI and the prevalence of cervical cancer.

“These findings suggest that dietary antioxidant intake may play a potential role in the prevention of cervical cancer. However, further prospective studies are needed to confirm this association and clarify the underlying mechanisms,” the authors wrote.

URL upon publication: https://onlinelibrary.wiley.com/doi/10.1002/ijgo.71276

How do body mass index and waist circumference affect mortality in older adults?

In a Journal of the American Geriatrics Society analysis of nationally representative data from 6,905 US adults aged 65 or older followed between 2011–2024, higher body mass index (BMI) was associated with lower mortality risk, whereas higher waist circumference, a marker of abdominal obesity, was independently associated with higher mortality risk after accounting for BMI.

Compared with normal weight, overweight males and males with class I and II obesity (BMI of 30 to less than 40 kg/m2) had 46% and 51% lower risks of mortality, respectively. Additionally, a high waist circumference was also associated with a 24% higher mortality risk in males. Similar patterns were observed in females.

When BMI and waist circumference were evaluated together, being overweight was associated with lower mortality risk regardless of waist circumference among males. Class I and II obesity also remined associated with lower mortality risk exclusively among males with elevated waist circumference. In contrast, being underweight, regardless of waist circumference, and having normal BMI with elevated waist circumference were both associated with higher mortality risk in both males and females.

"BMI and waist circumference provide complementary information about health risk in older adults,” said study co-author, Bryan Blissmer, PhD, of the University of Rhode Island. “Our findings suggest that considering both measures together, rather than relying on BMI alone, may improve mortality risk assessment and support more informed clinical decision-making.”

URL upon publication: https://onlinelibrary.wiley.com/doi/10.1111/jgs.70600

 

Physicians sue government to withdraw Dietary Guidelines for Americans

 

Guidelines violated federal law requiring transparency, balance, and evidence

 A “Secret Panel” of food-industry insiders handpicked by the Department of Health and Human Services and the U.S. Department of Agriculture illegally influenced the recommendations in the 2025-2030 Dietary Guidelines for Americans, argues a lawsuit the Physicians Committee for Responsible Medicine filed with the United States District Court for the District of Columbia on Aug. 19, 2026.

The Guidelines, released on Jan. 7, 2026, emphasize fats, meat, and dairy products, shocking many health experts. The “scientific foundation” for the Guidelines was hastily assembled by consultants with financial ties to the meat, dairy, and low-carb diet industries. 

“The government allowed the meat and dairy industries to ghostwrite the Dietary Guidelines,” said Physicians Committee President Neal D. Barnard, MD. “They put money in industry’s pocket and cholesterol in Americans’ arteries.”

In advance of each edition of the Dietary Guidelines, which are issued every five years by HHS and USDA, the agencies follow the Federal Advisory Committee Act (FACA) in establishing a Dietary Guidelines Advisory Committee (DGAC) to write a scientific report that serves as the foundation for the Dietary Guidelines.

In December 2024, after a transparent two-year public process, the DGAC’s 20 independent nutrition experts issued the Scientific Report of the 2025 Dietary Guidelines Advisory Committee, recommending in part that the Dietary Guidelines should advise Americans to consume more plant-based meals, prioritize beans and other plant-based protein over animal protein, and make water, rather than milk, their beverage of choice.

But instead of issuing Dietary Guidelines after reviewing the DGAC’s recommendations, HHS and USDA “disregarded federal law through a procedural bait and switch,” replacing the DGAC’s recommendations with “recommendations of a hastily assembled panel of industry insiders, without any oversight or input by the public,” according to the lawsuit.

The FACA mandates that an advisory committee “will not be inappropriately influenced by the appointing authority or any special interest,” but eight of the nine members of the Secret Panel had conflicts of interest including ties to the National Cattlemen’s Beef Association, the National Dairy Council, the American Egg Board, the National Pork Board, and the low-carbohydrate diet industry.

According to the lawsuit, the Secret Panel took “only three months to produce its 90 page report and 418 page appendix,” which was only made available, along with the names of the members of the Secret Panel, on Jan. 7, 2026, the day the Dietary Guidelines were released.

“The 2025–2030 Dietary Guidelines pose dangers to children, whose school food programs must adhere to the Dietary Guidelines; to individuals with medical conditions who might follow the baseless medical advice incorporated into the Dietary Guidelines; and to Americans who are at risk for diet-related diseases, including obesity, diabetes, and cardiovascular disease, and might follow the scientifically unfounded Dietary Guidelines, which are designed to promote fatty, high-cholesterol products of industries with which the Dietary Guidelines’ authors are affiliated,” argues the lawsuit.

The lawsuit asks the court to order HHS and USDA to withdraw the Dietary Guidelines and to forbid the agencies from using them in any future agency decisions while the agencies develop new Dietary Guidelines in compliance with the FACA.

“Industry-influenced Dietary Guidelines destroy any semblance of healthfulness in federal food programs like the National School Lunch Program, WIC, and SNAP,” says Dr. Barnard.

Prior to the issuance of the 2000 Dietary Guidelines, the Physicians Committee sued under the FACA and the Freedom of Information Act, arguing that six of the 11 DGAC members had financial ties to the meat, dairy, or egg industries and that these financial ties might increase the likelihood that unhealthy foods would remain in the Dietary Guidelines. A federal court agreed that the government had violated both laws. The Physicians Committee also challenged improprieties in the 2010, 2015, and 2020 Dietary Guidelines in federal court.

Founded in 1985, the Physicians Committee for Responsible Medicine is a nonprofit organization that promotes preventive medicine, conducts clinical research, and encourages higher standards for ethics and effectiveness in education and research.

Higher cardiorespiratory fitness = slower age-related decline in kidney function

 As Japan's population continues to age, age-related declines in kidney function and chronic kidney disease (CKD) are becoming increasingly prevalent, underscoring the need for effective preventive strategies. Despite growing interest in the health benefits of cardiorespiratory fitness, its relationship with future kidney function decline remains poorly understood, particularly among individuals with preserved kidney function. To address this gap, researchers investigated whether higher cardiorespiratory fitness, a measure of whole-body endurance capacity, is associated with a slower age-related decline in kidney function.

The study evaluated cardiorespiratory fitness using a submaximal cycling exercise test in 198 adults with preserved kidney function living in and around Ibaraki Prefecture and monitored changes in kidney function over a 5-year period. The results demonstrated that higher cardiorespiratory fitness was associated with a slower age-related decline in kidney function. Notably, this association remained significant after adjusting for potential confounding factors, including age, sex, body composition, smoking status, comorbidities, and baseline kidney function. The study also found that participants with higher cardiorespiratory fitness were less likely to experience a clinically meaningful decline in kidney function of ≥20% during the follow-up period.

These findings suggest that maintaining cardiorespiratory fitness while kidney function remains preserved may help protect kidney health later in life. From a sports medicine perspective, the results provide new insights into strategies for extending healthy life expectancy and mitigating age-related declines in kidney function, potentially contributing to the prevention of CKD. However, because this was an observational study, the findings do not establish a causal relationship between cardiorespiratory fitness and decline in kidney function.

Why you move — not just how often — could affect dementia risk

Physically strenuous work may not offer the same brain protection as voluntary leisure-time exercise and may even increase dementia risk.

Peer-Reviewed Publication

University of Southern California

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For years, scientists have known that regular physical activity can help lower the risk of dementia. But new USC research suggests that it’s not only the amount but also the activity’s context — for work or for leisure — that makes a difference.

A meta-analysis of more than 4.2 million people has found that leisure-time exercise — activities such as walking, cycling, running, swimming or playing sports — is associated with a substantially lower risk of dementia. In contrast, physical activity performed as part of a job appears to be linked with a higher risk of developing the condition.

Paradoxical results

The findings, published in The Lancet Public Health, are the first to systematically examine whether the so-called “physical activity paradox” extends to dementia. This paradox, well documented in cardiovascular research, describes the surprising observation that physically demanding jobs do not provide the same health benefits as voluntary exercise — and may even increase disease risk.

The research team, led by Professor of Biological Sciences and Anthropology David Raichlen of the USC Dornsife College of Letters, Arts and Sciences, analyzed data from 74 cohort and case-control studies involving more than 4.2 million participants aged 45 to 93 years across 30 countries. Participants were followed for a median of 10 years, during which investigators tracked diagnoses of all-cause dementia, Alzheimer’s disease and vascular dementia.

Overall, people who engaged in higher levels of leisure-time physical activity had a 24% lower risk of dementia than those who were least active. Household physical activity also appeared beneficial, although evidence came from only a single study. By contrast, occupational physical activity was associated with a 20% higher dementia risk, while active commuting showed a modest increase in risk, though those findings were based on just two studies.

“The findings challenge the long-held assumption that ‘every move counts’ for brain health,” said Natan Feter, the study’s first author, postdoctoral fellow in Raichlen’s Evolutionary Biology of Physical Activity Lab at USC and researcher in the Graduate Program of Epidemiology at Universidade Federal do Rio Grande do Sul (Brazil).

Work versus play

“Physical activity” often combines exercise, manual labor, housework and commuting into a single measure. But according to the researchers, these different forms of activity occur under very different circumstances and may have distinct effects on long-term health.

Leisure-time exercise is typically self-directed, can be performed at an enjoyable intensity and is often accompanied by social interaction or stress reduction. Physically demanding jobs, on the other hand, may involve repetitive tasks, prolonged standing, heavy lifting, limited recovery time and exposure to workplace hazards.

The authors argue that the apparent harms associated with occupational activity are unlikely to be caused by movement itself. Instead, they may reflect the broader social and environmental conditions that often accompany physically demanding work.

Manual occupations are more likely to involve psychosocial stress, lower job control, hazardous working conditions and greater exposure to air and noise pollution, all factors that have independently been linked to dementia risk. Workers in these jobs may also have fewer opportunities for recreational exercise because of time constraints, fatigue or limited access to safe places for physical activity.

Leisure-time exercise and occupational physical activity exhibited contrasting nonlinear associations with dementia risk. Higher levels of leisure-time exercise were associated with progressively lower dementia risk until the association plateaued, whereas higher levels of occupational physical activity were associated with progressively greater dementia risk before also plateauing.

Further investigation ahead

The authors note that evidence remains sparse for household and commuting activity, preventing firm conclusions about those domains. Likewise, most of the available research came from high-income countries, even though low- and middle-income countries are expected to experience the largest increases in dementia cases over coming decades.

Another limitation is that nearly all included studies relied on self-reported physical activity, which can introduce recall bias. Still, the consistency of the results across multiple sensitivity analyses gives confidence that the association should be taken seriously, Feter said.

Researchers caution that the results do not mean people should avoid physically active jobs. Because the analysis is based on observational studies, it cannot prove that occupational activity causes dementia. Instead, the findings highlight the importance of considering the context in which physical activity occurs. Leisure-time activity remained protective, while occupational activity remained associated with elevated dementia risk even after accounting for age, education and chronic diseases.

Additionally, research that Raichlen, Feter and colleagues published last month in the journal Alzheimer’s & Dementia indicates that the context of sedentary behavior may have an impact on brain structures. In that study, physically sedentary but mentally active behavior, such as working while seated at a desk, was associated with higher volume in regions of the brain’s cortex, including areas responsible for executive function, when compared to passive sedentary activity such as watching TV.

The findings indicate the importance of activity context and carry implications for public health, the authors emphasized. Rather than simply encouraging people to “move more,” dementia prevention efforts should recognize that not all physical activity occurs under the same conditions.

“In other words, when it comes to protecting the brain, the context of physical activity may matter just as much as movement itself,” Raichlen said. “Improving access to safe parks, walking trails and recreational facilities, ensuring people have adequate leisure time for exercise, and reducing harmful workplace exposures may ultimately prove as important as promoting physical activity itself.”