Tag: sex differences

Categories : Gender Pain ManagementTags :

Men and Women Use Different Biological Systems to Reduce Pain

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In a new study evaluating meditation for chronic lower back pain, researchers at University of California San Diego School of Medicine have discovered that men and women utilise different biological systems to relieve pain. While men relieve pain by releasing endogenous opioids, the body’s natural painkillers, women rely instead on other, non-opioid based pathways. The study was published in PNAS Nexus.

Synthetic opioid drugs, such as morphine and fentanyl, are the most powerful class of painkilling drugs available. Women are known to respond poorly to opioid therapies, which use synthetic opioid molecules to bind to the same receptors as naturally-occurring endogenous opioids. This aspect of opioid drugs helps explain why they are so powerful as painkillers, but also why they carry a significant risk of dependence and addiction.

“Dependence develops because people start taking more opioids when their original dosage stops working,” said Fadel Zeidan, PhD, professor of anaesthesiology and Endowed Professor in Empathy and Compassion Research at UC San Diego Sanford Institute for Empathy and Compassion. “Although speculative, our findings suggest that maybe one reason that females are more likely to become addicted to opioids is that they’re biologically less responsive to them and need to take more to experience any pain relief.”

The study combined data from two clinical trials involving a total of 98 participants, including both healthy individuals and those diagnosed with chronic lower back pain. Participants underwent a meditation training program, then practiced meditation while receiving either placebo or a high-dose of naloxone, a drug that stops both synthetic and endogenous opioids from working. At the same time, they experienced a very painful but harmless heat stimulus to the back of the leg. The researchers measured and compared how much pain relief was experienced from meditation when the opioid system was blocked versus when it was intact.

The study found:

  • Blocking the opioid system with naloxone inhibited meditation-based pain relief in men, suggesting that men rely on endogenous opioids to reduce pain.
  • Naloxone increased meditation-based pain relief in women, suggesting that women rely on non-opioid mechanisms to reduce pain.
  • In both men and women, people with chronic pain experienced more pain relief from meditation than healthy participants.

“These results underscore the need for more sex-specific pain therapies, because many of the treatments we use don’t work nearly as well for women as they do for men,” said Zeidan.

The researchers conclude that by tailoring pain treatment to an individual’s sex, it may be possible to improve patient outcomes and reduce the reliance on and misuse of opioids.

“There are clear disparities in how pain is managed between men and women, but we haven’t seen a clear biological difference in the use of their endogenous systems before now,” said Zeidan. “This study provides the first clear evidence that sex-based differences in pain processing are real and need to be taken more seriously when developing and prescribing treatment for pain.”

Source: University of California – San Diego

Categories : Gender Obstetrics & GynaecologyTags :

Boy or Girl? This Genetic Mutation Increases Odds of Having a Daughter

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Source: Pixabay CC0

Each year, roughly the same numbers of boys and girls are born. But in individual families, some couples have four or more daughters and no sons, and some have all male children and no female children, points out University of Michigan evolutionary geneticist Jianzhi Zhang. This has led some scientists to question whether this skewed sex ratio is a result of the genes of the parents.

Now, Zhang and U-M doctoral student Siliang Song have detected a human genetic variant that influences the sex ratio of children. Additionally, they found that many hidden genetic variants of sex ratio may exist in human populations. Their results are published in the Proceedings of the Royal Society B: Biological Sciences.

“Scientists have been pondering and researching a genetic basis for sex ratio for decades, yet no unambiguous evidence for a genetic variation that alters the human sex ratio from an approximately 50:50 ratio has been found,” said Zhang, professor of ecology and evolutionary biology.

Zhang says this has led some scientists to think that the human sex ratio is not subject to mutation.

“But this scenario seems unlikely, because almost all human characteristics are subject to mutation and genetic variation,” he said. “Instead, we think genetic variation of sex ratio is too difficult to detect because sex ratio is not measured precisely.”

That is, each person typically has a very small number of children, which can lead to large errors in the estimation of the true sex ratio of a person’s children. For example, if a person only has one child, the estimated sex ratio would be either zero (if it’s a girl) or 1 (if it’s a boy) even if the true sex ratio is 0.5.

To detect genetic influence on sex ratio, the researchers realised they needed a much larger sample than in all previous studies. They turned to the UK Biobank, a biomedical database that contains the genetic and phenotypic information of about 500 000 British participants.

Analysing this data, the researchers identified a single nucleotide change named rs144724107 that is associated with a 10% increase in the probability of giving birth to a girl as opposed to a boy. But this nucleotide change is rare among the UK Biobank participants: About 0.5% of the participants carry this change. The nucleotide change is located near a gene named ADAMTS14, which is a member of the ADAMTS gene family known to be involved in spermatogenesis and fertilisation. The researchers also note that their discovery has not yet been confirmed in other samples.

The researchers also identified two genes, called RLF and KIF20B, that may also influence the sex ratio.

The study’s findings align with a theory in evolutionary biology called Fisher’s principle, which states that natural selection favours the genetic variant that increases the births of the rare sex. That is, if fewer males than females are born in a population, natural selection favours genetic variants that increase the number of males born, and vice versa. As a result, this selection yields a more or less even sex ratio in the population

“For Fisher’s principle to work, there must be mutations that influence the sex ratio,” Zhang said. “The fact that no genetic variation on human sex ratio had been identified has led some scientists to question the applicability of Fisher’s principle in humans.

“Our study shows that in fact, human data are consistent with Fisher’s principle and the reason no genetic variants of sex ratio had been discovered was the imprecision of the measure of a person’s offspring sex ratio.”

Next, the researchers hope to verify their findings in other samples – not an easy task, Zhang says, because of the large sample size requirement and the rareness of the identified genetic variant.

Source: University of Michigan

Categories : Diet and NutritionTags :

Avo at Breakfast for Women, Oats for Men, Study Suggests

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New research from the University of Waterloo suggests that men and women should have different kinds of food for breakfast in order to help lose weight.

The study, which employed a mathematical model of men’s and women’s metabolisms, showed that men’s metabolisms respond better on average to a meal laden with high carbohydrates like oats and grains after fasting for several hours, while women are better served by a meal with a higher percentage of fat, such as omelettes and avocados. The findings are out now in Computers in Biology and Medicine.

“Lifestyle is a big factor in our overall health,” said Stéphanie Abo, an Applied Mathematics PhD candidate and the lead author of the study. “We live busy lives, so it’s important to understand how seemingly inconsequential decisions, such as what to have for breakfast, can affect our health and energy levels. Whether attempting to lose weight, maintain weight, or just keep up your energy, understanding your diet’s impact on your metabolism is important.”

The study builds on an existing gap in research on sex differences in how men and women process fat. “We often have less research data on women’s bodies than on men’s bodies,” said Anita Layton, a professor of Applied Mathematics and Canada 150 Research Chair in Mathematical Biology and Medicine.

“By building mathematical models based on the data we do have, we can test lots of hypotheses quickly and tweak experiments in ways that would be impractical with human subjects.”

“Since women have more body fat on average than men, you would think that they would burn less fat for energy, but they don’t,” said Layton. “The results of the model suggest that women store more fat immediately after a meal but also burn more fat during a fast.”

Going forward, the researchers hope to build more complex versions of their metabolism models and extend beyond the consideration of biological sex by incorporating an individual’s weight, age, or stage in the menstrual cycle.

Source: University of Waterloo

Categories : CancerTags :

How, When and Where: Sex Matters in Melanoma Development

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Melanoma rates differ consistently between men and women in terms of the ages at which melanomas occur and the locations on the body where they occur. Over time, melanoma rates have increased in both men and women, but the trends differ by body site. A new study in the Journal of Investigative Dermatology, published by Elsevier, presents the findings from a large-scale, long-term melanoma data analysis investigating incidence trends by age, sex, and anatomic site.

Lead investigator David C. Whiteman, MBBS, PhD, Cancer Control Group, QIMR Berghofer Medical Research Institute, and Faculty of Medicine, The University of Queensland, Brisbane, Australia, explains, “There has been a general observation in numerous populations that melanomas appear to arise at different rates in men and women. We decided to investigate this observation rigorously and assess whether these differences have been constant through time or across generations by using large-scale data from population registries to investigate long-term melanoma trends in men and women.”

The research team analysed more than 40 years of melanoma data from Queensland, Australia, the USA, and Scotland. These three populations were chosen because historically they have had high (Queensland), moderate (USA), and low (Scotland) rates of melanoma. Over time, the rates of melanoma increased in all three populations, especially among women. In women in all populations, melanomas arise most commonly on the limbs, whereas in men, melanomas arise most commonly on the trunk and head and neck. In both sexes, there has been a steady increase in melanomas on the head and neck with increasing age.

Researchers found that in virtually all investigated populations, women experience higher rates of melanoma than men in early life (up to age ~45 years), but men develop melanomas at higher rates than women later in life (from ages ≥ 65 years). Furthermore, these sex-specific trends reflect complex patterns of incidence across body sites that vary consistently with age. Thus, in early life, women experience higher rates of lower limb melanomas than men, which persists into older ages. Also, on the upper limbs, women experience substantially higher rates than men from young ages until middle age (45–64 years), after which men experience higher rates. In contrast, on the head and neck and the trunk, melanomas occur at higher incidence in men than in women early in life. On all body sites, the rate at which melanoma incidence rises with age is much more rapid for men than for women.

The study confirms that men and women experience melanoma in different ways. While this is most likely driven by different patterns of sun exposure between men and women, there appear to be inherent differences in the ways in which melanomas develop at different body sites in women compared with men. Understanding the underlying biological differences could provide important clues about the etiology of this enigmatic cancer.

Source: Elsevier

Categories : Environmental Effects GenderTags :

Older Women more Vulnerable to Heat than Men, Researchers Find

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As global climate change causes extreme heat waves to become more common around the world, epidemiological studies have shown that heat kills more women than men. Now, a new study by researchers at Penn State has found that older women are physiologically more vulnerable to high heat and humidity than older men, and that women between the ages of 40 and 64 are as vulnerable as men 65 years of age or older. This is the first study to determine this disparity exists due to physiological differences rather than from a preponderance of women at old age due to greater longevity.

Led by Olivia Leach, doctoral candidate in kinesiology at Penn State, and her adviser, W. Larry Kenney, professor of physiology and kinesiology at Penn State, the researchers demonstrated that middle-aged and older women were affected by heat at lower temperature/humidity combinations than middle-aged and older men. The results, published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, were somewhat unexpected, according to Leach, because there are no differences in heat vulnerability based on biological sex in adults younger than 30.

While the researchers did not directly compare middle-aged men to middle-aged women, the physiological responses of middle-aged women were similar to the responses of older men in the study, which demonstrated that middle-aged women are more vulnerable to heat than men of the same age.

“In addition to demonstrating that middle-aged and older women are at greater risk from extreme heat, we also identified what levels of heat and humidity are safe for women as they age,” Leach said. “This information is presented as a temperature/humidity curve based on a person’s age, and it can be useful for setting policies designed to keep people safe during a heat wave.”

The researchers tested the heat thresholds of 72 participants between 40 and 92 years of age in a specialized environmental chamber in Kenney’s laboratory. Before the experiment, participants swallowed a tiny device encased in a capsule that measured their core temperature throughout the experiment.

During the study, participants entered the specialised environmental chamber where they performed light physical activity to simulate the effort of minimal day-to-day tasks – the types of things people would need to do even during a heat wave. The researchers then gradually increased the temperature and/or humidity in the chamber until the participant’s body could no longer adequately cool itself, and their core temperature began to rise.

The study is part of the PSU HEAT, or Human Environmental Age Thresholds, project, led by Kenney. For five years, researchers in the PSU HEAT project have examined the levels of combined heat and humidity that humans can tolerate before their core temperatures begin to rise. When core temperatures rise, people become vulnerable to heat-related illnesses including heat exhaustion, heat stroke and even death.

“We’re not saying that people who experience a certain temperature will necessarily become sick or die,” Kenney said. “We are identifying the limits of livability – the thresholds where people can no longer continue their daily life unimpeded. Once people reach these temperatures, they need to take actions like seeking air conditioning to cool their bodies.”

Previous research by Kenney and others demonstrated that people become increasingly vulnerable to heat as they age, because their ability to efficiently sweat and pump blood to the skin – two primary cooling mechanisms – decreases. Sweat evaporation carries heat away from the body, while extra blood pumped to the skin dissipates heat to the environment and supports sweating.

To date, the PSU HEAT project has conducted more than 600 experiments on nearly 200 participants between ages 18 and 92, but the results of this experiment still yielded surprises, according to Leach.

“Among young adults, there is no difference in heat vulnerability between men and women,” Leach said. “Young people tend to be healthier, so any measurable health metric – from blood pressure to cholesterol – is more homogeneous among young people than it is among older people.”

As with other health measures, older adults have a wide range in their vulnerability to heat, Leach explained.

“We have examined many factors that might explain who faces the most risk in a heat wave,” Leach said. “We found that age and biological sex are the two most important factors that can predict whether a healthy adult would be at risk from high heat and humidity.”

While cardiovascular health and certain medications can affect a person’s sensitivity to heat, biological sex and age appear to be the two primary drivers of heat vulnerability among healthy people, the researchers said.

“Other factors – for example someone’s cardiovascular fitness or their body mass – have little impact on how vulnerable a person is to heat at rest or during light activity,” Leach continued. “Older women really are at greater risk from heat than other people. As governments and other social leaders prepare for extreme heat to become more common, the vulnerability of older women needs to factor into their planning.”

Source: Penn State

Categories : Gender Immune SystemTags :

New Research Explains Differences in Men’s and Women’s Immune Systems

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By analysing the immune system of female-to-male transgender individuals, Swedish researchers demonstrate the role of sex hormones in regulating the immune system. This newfound knowledge, published in Nature, explains differences between men and women, particularly in terms of immune signalling, and can be used to develop new immunological medications according to researchers.

Sex differences in the immune system are regulated both by genetics and by sex hormones. However, immunological comparisons between men and women can never fully distinguish the significance of genetic versus hormonal variations.

Now, three Swedish research groups led by Karolinska Institutet and Uppsala University has conducted a unique study analysing the regulation and adaptation of the immune system over time in 23 trans men who have undergone gender-affirming testosterone treatment, starting at the age of 18–37 years.

“We have followed individuals who were assigned female sex at birth and later received testosterone treatment in adulthood. Their genetic profile remains unchanged, while their hormone profile shifts entirely from typically female to male hormone levels,” says Petter Brodin, paediatrician and professor of paediatric immunology at the Department of Women’s and Children’s Health, Karolinska Institutet, who led the study together with Nils Landegren, assistant professor at Uppsala University, and Olle Kämpe, Professor at the Department of Medicine, Solna, Karolinska Institutet. “This unique change allows us, for the first time, to identify which parts of a person’s immune system are directly regulated by sex hormones rather than genetic sex differences.” 

The researchers can now demonstrate that increased testosterone levels and the accompanying reduction in oestrogen particularly affect the balance between two crucial immune signalling systems: antiviral interferon type 1 (IFN-1) and proinflammatory signals such as tumour necrosis factor alpha (TNFα).  

Specifically, they found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. 

The immune system changes throughout life

They also have a hypothesis about why the immune system needs to be dynamically regulated by hormones throughout life. 

“All individuals must be able to adjust their immune systems over the course of their lives to be optimally regulated for the conditions and challenges we face. During puberty and sexual maturation, new demands arise, and the immune system must be regulated differently to enable pregnancy in women and muscle growth in men,” says Petter Brodin. 

By regulating these key functions via sex hormones, this can be achieved, and in women, it is dynamically controlled even during a menstrual cycle,” he adds. 

The results of the study open an entirely new field of research, according to Nils Landegren. 

“The newfound knowledge will help us better influence people’s immune systems even without using sex hormones. For example, new drugs can be developed to impact these regulatory mechanisms and thus rebalance the immune response, especially for women with the autoimmune rheumatic disease SLE,” he explains. 

However, the results also have a more direct implications for transgender individuals. 

“This research is also of crucial for transgender individuals undergoing gender-affirming hormone therapy, and I believe that this group deserves significantly more scientific attention and follow-up to ensure their long-term health,” says Petter Brodin. 

Source: Karolinska Institutet

Categories : Metabolic DisordersTags :

Oestrogen’s Protection against Fatty Liver Points to New Drug Treatment

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New research from Karolinska Institutet shows how oestrogen protects against MASLD, a fatty liver disease on the increase in the obesity epidemic. The study, published in Molecular Systems Biology, shows how a new drug under development could become a future treatment for fatty liver disease and liver cancer.

The global obesity epidemic has resulted in a dramatic increase in fatty liver, a disease in which fat that does not fit into fat cells is stored in liver cells instead.

Since last year, fatty liver due to obesity (and not excessive alcohol consumption) is known as MASLD (metabolic dysfunction-associated steatotic liver disease). According to previous research, as many as one in three adults are affected by some degree of MASLD, which in the worst cases can develop into cirrhosis and liver cancer.

Protection until menopause

However, the disease is very unevenly distributed between the sexes, with a large majority of affected individuals being men.

“Women have a natural protection until menopause due to the female sex hormone oestrogen,” explains study leader Claudia Kutter, senior researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

Although women’s protection has been known for some time, the mechanism behind the protective effect has been less clear. Now Claudia Kutter’s research team may have found the answer.

Through genetic analyses of mice of both sexes fed a high-fat diet, with some of the male mice also receiving oestrogen, the researchers were able to identify a key protein in the development of fatty liver. 

The protein, called TEAD1, was found to play an overall role in regulating how liver cells absorb fat. Blocking TEAD1 protected liver cells from the harmful accumulation of fat. Mice receiving oestrogen treatment had lower TEAD1 activity and less fat accumulation in the liver.

New drug under development

In the next step, the researchers tested blocking TEAD1 in human liver cells with the same result. The fact that this was possible at all, however, was a bit of luck.

“It turned out that a pharmaceutical company is developing an anti-cancer drug that blocks TEAD1, which allowed us to test our hypothesis,” says Claudia Kutter.

The fact that TEAD1 is also involved in cancer does not worry her, quite the contrary.

“Since the activity of TEAD proteins is elevated in cancer, blocking TEAD at an early stage can also be positive from a cancer point of view,” she says. “Patients suffering from liver cancer are currently diagnosed very late. If the patient is given this drug early in the process to protect against fatty liver, it can hopefully also prevent the development of liver cancer.”

The pharmaceutical company will now start clinical trials of the drug as a protection against fatty liver disease, while Claudia Kutter’s research team will continue researching further ways to tackle the disease.

“We want to focus on how to find the disease earlier and identifying new treatment targets,” she says. “Different approaches may be needed for different patients depending on their gender and hormonal status.”

Source: Karolinska Institutet

Categories : Exercise Skeletal SystemTags :

The Arms and Torso of Human Males Evolved to Throw a Punch

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Photo by Hermes Rivera on Unsplash

In the animal kingdom, males develop specialised weapons such as deer antlers for competition when winning a fight is critical. Humans do too, according to new research from the University of Utah. Males’ upper bodies are built for more powerful punches than females’, says the study, published in the Journal of Experimental Biology, suggesting that fighting may have long been a part of our evolutionary history.

“In mammals in general,” says professor David Carrier of the School of Biological Sciences, “the difference between males and females is often greatest in the structures that are used as weapons.”

Assembling evidence

For years, Carrier has been exploring the hypothesis that generations of interpersonal male-male aggression long in the past have shaped structures in human bodies to specialise for success in fighting. Past work has shown that the proportions of the hand aren’t just for manual dexterity- they also protect the hand when it’s formed into a fist. Other studies looked at the strength of the bones of the face (as a likely target of a punch) and how our heels, planted on the ground, can confer additional upper body power.

“One of the predictions that comes out of those,” Carrier says, “is if we are specialised for punching, you might expect males to be particularly strong in the muscles that are associated with throwing a punch.”

Jeremy Morris, then a doctoral student and now an assistant professor at Wofford College, designed an experiment with Carrier, doctoral student Jenna Link and associate professor James C. Martin to explore the sexual dimorphism, or physical differences between men and women, of punching strength. It’s already known that males’ upper bodies, on average, have 75% more muscle mass and 90% more strength than females’. But it’s not known why.

“The general approach to understanding why sexual dimorphism evolves,” Morris says, “is to measure the actual differences in the muscles or the skeletons of males and females of a given species, and then look at the behaviours that might be driving those differences.”

Cranking through a punch

To avoid potential hand injury from a using punching bag, the researchers instead rigged up a hand crank that would mimic the motions of a punch. They also measured participants’ strength in pulling a line forward over their head, akin to the motion of throwing a spear. This tested an alternative hypothesis that males’ upper body strength may have developed for the purpose of throwing or spear hunting.

Twenty men and 19 women participated. “We had them fill out an activity questionnaire,” Morris says, “and they had to score in the ‘active’ range. So, we weren’t getting couch potatoes, we were getting people that were very fit and active.”

But even with roughly uniform levels of fitness, the males’ average power during a punching motion was 162% greater than females’, with the least-powerful man still stronger than the most powerful woman. Such a distinction between genders, Carrier says, develops with time and with purpose.

“It evolves slowly,” he says, “and this is a dramatic example of sexual dimorphism that’s consistent with males becoming more specialised for fighting, and males fighting in a particular way, which is throwing punches.”

They didn’t find the same magnitude of difference in overhead pulling strength, lending additional weight to the conclusion that males’ upper body strength is specialised for punching rather than throwing weapons.

Breaking a legacy of violence

It’s an uncomfortable thought to consider that men may be designed for fighting. That doesn’t mean, however, that men today are destined to live their ancestor’s violent lives.

“Human nature is also characterized by avoiding violence and finding ways to be cooperative and work together, to have empathy, to care for each other, right?” Carrier says. “There are two sides to who we are as a species. If our goal is to minimise all forms of violence in the future, then understanding our tendencies and what our nature really is, is going to help.”

Source: University of Utah

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Women Lose More Years of Life After a Heart Attack Than Men

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A new study shows that women lose more years of life after a heart attack than men. A 50-year-old woman with a large heart attack loses an average of 11 years, while an 80-year-old man with a small heart attack loses an average of 5 months of life. The results of the study, led by researchers at Karolinska Institutet and Danderyd Hospital, are published in the journal Circulation.

The new study examined 335 000 individuals with first-time myocardial infarction registered in the SWEDEHEART quality registry during the period 1991-2022. The individuals with myocardial infarction were compared with 1.6 million individuals without myocardial infarction using data from Statistics Sweden and the National Board of Health and Welfare. Using the comparator population and new statistical methods, the difference in life expectancy between heart attack individuals and comparison individuals could be calculated, providing a measure of how much life expectancy was shortened due to the disease. 

“We found that there were large differences between groups. Women and young individuals lost the most life expectancy when they had a heart attack. If the cardiac function was impaired after the infarction, the effects were even greater. For example, a 50-year-old woman with impaired cardiac function loses an average of 11 years in 2022 compared to an 80-year-old man with normal cardiac function who loses an average of 5 months in life expectancy,” says first author Christian Reitan, researcher at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institut. 

Parameters affecting heart attack risk

The researchers were also able to take into account differences in income, education, other illnesses and medication at the time of the illness – which helped to measure the effect of the heart attack itself when everything else was taken into account.

“The results showed that a fairly large part of the reduction in life expectancy disappeared, that is, much of the reduction in life expectancy is explained by factors other than the heart attack itself, but which may still be associated with heart attack, such as socioeconomics or other diseases such as hypertension and diabetes. Provided that the patient had preserved cardiac function, we saw that the gender difference had disappeared. We interpret this to mean that the effect of the heart attack, and thus also the care for heart attacks, is similar between the sexes and that the large reduction in life expectancy we see in women is due to differences in risk factors, other diseases and socioeconomics,” says Christian Reitan. 

According to the researchers, there is a lack of individualized heart attack care in Sweden for women. The study shows that women who have a heart attack lose more years of life than men of the same age.

“If a woman had impaired cardiac function, the gender difference was large. We don’t have the data to answer why, but it raises questions about whether women get as good follow-up and treatment for heart failure as men, or whether it is simply a more serious condition for a woman. Our findings are important because they challenge existing guidelines for heart attack treatment today. By identifying high-risk groups, we can hopefully better tailor treatment to the individual. We believe that ‘years of life lost’ is a good and easy-to-understand measure of risk for both doctors and patients. It makes it easier for us to assess and communicate the seriousness of the disease,” concludes Christian Reitan. 

Source: Karolinska Institutet

Categories : Neurodegenerative DiseasesTags :

Those with Alzheimer’s Disease History on Mother’s Side have Increased Amyloid Proteins

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Neurons in the brain of an Alzheimer’s patient, with plaques caused by tau proteins. Credit: NIH

A new study by investigators from Mass General Brigham suggests that whether a person inherits risk of Alzheimer’s disease from their mother or father influences risk of biological changes in the brain that lead to disease. By evaluating 4400 cognitively unimpaired adults ages 65–85, the team found those with a history of Alzheimer’s disease (AD) on either their mother’s side or both parents’ sides had increased amyloid in their brains. Their results are published in JAMA Neurology.

“Our study found if participants had a family history on their mother’s side, a higher amyloid level was observed,” said senior corresponding author Hyun-Sik Yang, MD, a neurologist at Mass General Brigham.

Yang said that previous smaller studies have investigated the role family history plays in Alzheimer’s disease. Some of those studies suggested maternal history represented a higher risk of developing Alzheimer’s, but the group wanted to revisit the question with cognitively normal participants and access to a larger clinical trial data set.

The team examined the family history of older adults from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial aimed at AD prevention. Participants were asked about memory loss symptom onset of their parents. Researchers also asked if their parents were ever formally diagnosed or if there was autopsy confirmation of Alzheimer’s disease.

“Some people decide not to pursue a formal diagnosis and attribute memory loss to age, so we focused on a memory loss and dementia phenotype,” Yang said.

Researchers then compared those answers and measured amyloid in participants. They found maternal history of memory impairment at all ages and paternal history of early-onset memory impairment was associated with higher amyloid levels in the asymptomatic study participants. Researchers observed that having only a paternal history of late-onset memory impairment was not associated with higher amyloid levels.

“If your father had early onset symptoms, that is associated with elevated levels in the offspring,” said Mabel Seto, PhD, first author and a postdoctoral research fellow in the Department of Neurology at the Brigham. “However, it doesn’t matter when your mother started developing symptoms – if she did at all, it’s associated with elevated amyloid.”

Seto works on other projects related to sex differences in neurology. She said the results of the study are fascinating because Alzheimer’s tends to be more prevalent in women. “It’s really interesting from a genetic perspective to see one sex contributing something the other sex isn’t,” Seto said. She also noted the findings were not affected by whether study participants were biologically male or female.

Yang noted one limitation of the study is some participants’ parents died young, before they could potentially develop symptoms of cognitive impairment. He said social factors like access to resources and education may have also played a role in when someone acknowledged cognitive impairment and if they were ever formally diagnosed.

“It’s also important to note a majority of these participants are non-Hispanic white,” Seto added. “We might not see the same effect in other races and ethnicities.”

Seto said the next steps are to expand the study to look at other groups and examine how parental history affects cognitive decline and amyloid accumulation over time and why DNA from the mother plays a role.

Reisa Sperling, MD, a co-author on the paper, principal investigator of the A4 Study and a neurologist at Mass General Brigham, said the findings could be used soon in clinical translation.

“This work indicates that maternal inheritance of Alzheimer’s disease may be an important factor in identifying asymptomatic individuals for ongoing and future prevention trials,” Sperling said.

Source: Mass General Brigham