Not Just A Matter Of Age
Why are women at greater risk for dementia? It’s a simple question with complex answers and many unknowns.
For decades, experts assumed the increased prevalence of Alzheimer’s disease among women was a consequence of their living longer than men. And while that may be partially true given that advancing age is the primary risk factor it’s not the only reason.
“The social and environmental influences on health play a huge role in brain health for women, notes Sarah Lenz Lock, senior vice president for policy and brain health at AARP and executive director of the GCBH. Women face more challenges due to lower educational levels, they have fewer economic resources, they provide more caregiving for their families and they experience more stress and these factors can have an effect on the risk of cognitive decline.
A woman’s reproductive history including the age at which she got her first menstrual period, how many successful pregnancies she had, and the age at which she reached menopause may play a role in her risk of developing dementia. While the GCBH report acknowledges that more research needs to be done to investigate the effects of pregnancy and childbearing on a woman’s risk of developing dementia, some research already suggests that women who have three or more children have a 12 percent lower risk of dementia compared to women who have one child.
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Risk Factors Beyond Longevity
Until now, the gap had been largely attributed to the longevity of women, since age is the number one risk factor for Alzheimers. Roberta Diaz Brinton, a University of Southern California professor who studies gender differences said, It is true that age is the greatest risk factor for developing Alzheimers disease. But she went on to say, on average, women live four or five years longer than men and we know that Alzheimers is a disease that starts 20 years before the diagnosis.
Thus far, genetic studies have offered a startling account for the difference. Researchers from Stanford University studied over 8,000 people looking for a form of the gene ApoE-4, a gene that increases the risk of Alzheimers. They found that women who carry a copy of that particular gene variant were twice as likely to eventually develop Alzheimers as women without the gene. Men who had the gene were only at a slightly increased risk than men who did not have the gene. While it is not clear why the gene poses such a drastic increase in risk, Brinton believes it may be how the gene interacts with estrogen.
Another study suggests that it may be related to heart health. A study from Framingham, Massachusetts suggests that because men are more likely to die from heart disease in middle age, those men who live past 65 may have healthier hearts which may protect the brain from Alzheimers. These two diseases share many risk factors including high cholesterol, diabetes, and obesity.
How Is Alzheimers Disease Treated
Medical management can improve quality of life for individuals living with Alzheimers disease and for their caregivers. There is currently no known cure for Alzheimers disease. Treatment addresses several areas:
- Helping people maintain brain health.
- Managing behavioral symptoms.
- Slowing or delaying symptoms of the disease.
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The Gene Linked To Alzheimers
To understand if other genes involved in tau-related diseases are related to AD risk in women, the researchers performed GWAS on two different populations:
- 31 members of the Hutterites, a group of people with common ancestry, recognized for their relatively small gene pool, 22 of whom were women.
- 10,340 women without APOE 4, who were part of the Alzheimers Disease Genetics Consortium . These included 3,399 AD cases and 6,905 controls.
Researchers found that in both populations, the MGMT gene was associated with AD risk in women lacking APOE 4.
The fact that studies with such different designs identified genetic variants that were linked to the same gene was unexpected, said Dr. Carole Ober, chair of human genetics at the University of Chicagoand joint study lead.
The different lines of evidence supporting a role for MGMT in Alzheimers disease risk increased our confidence, she said.
The work suggests that the expression of MGMT contributes to the development of toxic amyloid and tau proteins associated with the development of AD.
, 58 with confirmed AD.
Speaking to Medical News Today about the mechanisms behind the findings, Dr. Ober explained:
Our data suggest that the associated genetic variants affect levels of DNA methylation and/or other epigenetic marks, like open chromatin, and these epigenetic changes impact the expression of MGMT at key developmental stages is our current working hypothesis.
Brain Changes Appear Years Earlier In Women Than In Men Imaging Shows
byJudy George, Senior Staff Writer, MedPage Today June 24, 2020
Women developed Alzheimer’s disease-related brain changes earlier than men, a cross-sectional imaging study showed.
Compared with their male counterparts, cognitively normal middle-age women showed higher beta-amyloid loads, lower glucose metabolism, and lower gray and white matter volumes, said Lisa Mosconi, PhD, of Weill Cornell Medicine in New York City, and colleagues.
Menopause was the strongest predictor of Alzheimer’s brain changes, they reported in Neurology.
Alzheimer’s disease affects more women than men. “For every man suffering with Alzheimer’s, there are two women,” Mosconi said. “For a long time, the general mindset was that women live longer than men, and Alzheimer’s is a disease of old age, and that’s why the prevalence is higher in women.”
But Alzheimer’s is not a disease of the old, Mosconi emphasized. “It starts with negative changes in the brain years — if not decades — before clinical symptoms emerge,” she told MedPage Today.
“In this study, we show for the first time that women develop Alzheimer’s-related changes in their brains earlier than men do,” she said. “So, it isn’t just that women live longer we also start showing the tell-tale signs of Alzheimer’s earlier on in life, specifically in midlife.”
“It’s unclear when these sex differences might begin to appear,” she noted. “Is the key related to the menopausal transition?”
Disclosures
Primary Source
Neurology
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The Impact Of Caregiving
Finally, a discussion of ADs effects on women must acknowledge womens disproportionately large caregiving role. Women account for three out of every five AD caregivers. This means that about 6.7 million women in America provide unpaid care for someone with dementia.7 The impact on these caregivers lives is extraordinarily stressful. An NAC/AARP poll taken in 2010 showed that nearly half the caregivers who responded considered the stress of caregiving to be maximal.8 Many employed caregivers are forced to take a leave of absence from a paid job or to give up a job altogether as a result of caregiving demands. The majority of caregivers report having less time for their friends and families.
Dementia & Alzheimer’s Disease
You should be aware of the most common signs of dementia in women as the disease affects the female population more.
Even to this day, there is still no cure that would help prevent dementia. However, if we are familiar with the symptoms, we can take action early on and mitigate the condition.
Fun fact: there are approximately twice as many women with dementia compared to men. That said, brain cells in the brain of a woman are dying much faster.
Although women live longer than men, dementia is not really an aging disease rather solely related to the brain itself.
With all the information you will gain throughout this article, you can contribute to the care and treatment of a person with dementia.
You will now at least know that if any of the symptoms from the list below appear in your loved ones, it would be advisable to call a doctor.
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What Is Known About Reducing Your Risk Of Alzheimers Disease
The science on risk reduction is quickly evolving, and major breakthroughs are within reach. For example, there is growing evidence that people who adopt healthy lifestyle habits like regular exercise and blood pressure management can lower their risk of dementia. There is growing scientific evidence that healthy behaviors, which have been shown to prevent cancer, diabetes, and heart disease, may also reduce risk for subjective cognitive decline. To learn more about the current state of evidence on dementia risk factors and the implications for public health, please read the following summaries on Cardiovascular Health, Exercise, Diabetes and Obesity, Traumatic Brain Injury , Tobacco and Alcohol, Diet and Nutrition, Sleep, Sensory Impairment, and Social Engagement or the Compiled Report .
Aging
Hormone Replacement Therapy And Dementia
Oestrogen and progesterone are commonly used in hormone replacement therapy . Some women going through menopause choose this to help relieve some of the symptoms, such as hot flushes and anxiety.
HRT fell out of favour after a Womens Health Initiative study in 2002 found that it increased the level of risk of heart disease, and breast cancers. However, since then different types of HRT have been developed that are much safer. Now that HRT carries less risk, there are less concerns about its safety when considering its potential benefits for dementia risk.
Previous research into the link between HRT and dementia risk is conflicting with studies producing mixed results. However, in 2021 a large study of nearly 400,000 women, found both new and old HRT drugs reduced the risk of diseases that cause dementia. The study found that the effects differed based on many things: dose, type of medication, length of treatment, age and time from menopause. Now, researchers are currently working to understand the link better, to clarify whether HRT really does reduce dementia risk.
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Does Heart Health Play A Role In Dementia Risk
We know that what is good for the heart is good for the head. Improving heart health seems to be a good way to lower dementia risk. The health of a heart affecting dementia risk might also be linked to sex. For example, high blood pressure in midlife is believed to increase risk in women but not men, even though it is more common in men.
Professor Patrick Kehoe is an Alzheimers Society funded researcher based at University of Bristol. He says:
‘It is possible that the complex relationship of oestrogen to the renin angiotensin system, which regulates blood pressure and has roles in cognitive function, influences a womans risk of developing Alzheimers. Following menopause with the influence of oestrogen on this system a woman is at greater risk of high blood pressure and so perhaps also dementia, but we need to test this in more detail.
What Is Alzheimers Disease
- Alzheimers disease is the most common type of dementia.
- It is a progressive disease beginning with mild memory loss and possibly leading to loss of the ability to carry on a conversation and respond to the environment.
- Alzheimers disease involves parts of the brain that control thought, memory, and language.
- It can seriously affect a persons ability to carry out daily activities.
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Women And Alzheimers Disease
Consider the following statements:
- Women over the age of 60 are twice as likely to develop Alzheimers disease as they are to develop breast cancer. There are survivors of cancer but there are not yet survivors of Alzheimers disease.
- Two thirds of the population living with Alzheimers disease are female.
What makes women more susceptible to Alzheimers disease than men? The previous thinking was that women simply lived longer than men. However, recent research suggests some interesting alternative explanations.
Advances in science and technology have allowed investigators to discover important biological differences between women and men that are changing our fundamental understanding of Alzheimers disease. According to recent studies, women appear to have increased genetic risk for Alzheimers disease compared with men. In addition, women may be more susceptible to some aspects of disease progression. But at the same time, they may also be more resistant to experiencing the symptoms of the disease.
The explanation is complex, and may include a variety of factors biological, genetic and social.
How Alzheimers Affects Women Differently
Its not exactly clear why women are more affected by Alzheimers than men, but there may be several factors at play. According to Dr. Caldwell, women tend to decline faster than men after receiving a diagnosis for Alzheimers. Women typically live longer than men, too, and while the No. 1 risk factor for Alzheimers is aging, that may not be the whole story.
Some of the reasons might be artifacts of our diagnostic systems, says Dr. Caldwell. For example, we know women tend to have better verbal memory than men, and our tests rely on verbal memory. So, it is possible that women dont get diagnosed as early because our tests miss those important verbal memory changes.
In addition, menopause and estrogen loss are a huge area of investigation for Alzheimers because estrogen supports an area of the brain responsible for forming new memories. Its this part of the brain thats first targeted when Alzheimers develops, so as women age, they may be even more affected. Plus, women have a greater increase in Alzheimers risk, compared to men, when they carry a gene associated with late-onset Alzheimers. But on the other hand, there is a line of research that suggests having two X-chromosomes might put women at an advantage.
Theres not a simple, straightforward story, says Dr. Caldwell. We are going to have to look at Alzheimers as involving our genetics, our environment as well as our own behaviors.
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Alzheimers Disease Is A Progressive Disabling Degenerative Disorder Of The Brain More Than 6 Million Americans Are Currently Living With Alzheimers Disease And The Majority Of Them Are Women
Additionally, while Alzheimers is the eighth leading cause of death for men, it is the fifth leading cause of death for women. A growing body of research confirms that biological sex plays a role in disease risk, as well as presentation and progression of dementia. Scientists are exploring the causes of these sex disparities, but we still do not understand much about the role sex plays in etiology and prognosis.
SWHRs Alzheimers Disease Network is working to raise awareness about these biological sex disparities and create recommendations for future research and policies related to womens health and Alzheimers disease.
A Healthy Lifestyle May Offset Genetic Risk For Alzheimers
Using scans on more than 1,000 older adults, they found sex differences in how the brain uses sugar, its main energy source. Women metabolized sugar better, which may give them more ability to compensate for the damage from dementia and make them less likely to be diagnosed with it by tests that involve verbal skills.
The female advantage might mask early signs of Alzheimers and delay diagnosis, said study leader Erin Sundermann. Women are able to sustain normal verbal performance longer, partly because of better brain metabolism.
At the University of Miami, scientists analyzed genes in 30,000 people half with Alzheimers, half without it and found four that seem related to disease risk by sex.
One confers risk in females and not males and three confer risk in males but not females, said one study leader, Eden Martin.
Researchers dont know yet exactly how these genes affect risk or by how much.
Some of these look like theyre tied to the immune system and we know there are differences between males and females in how that works, said another study leader, Brian Kunkle.
Seven other genes seem to have different effect on risks in men versus women. The researchers have a National Institute on Aging grant to do an international study on nearly 100,000 people to try to validate and extend the results.
Marilynn Marchione
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Hypertensive Disorders In Pregnancy Up Dementia Risk
Megan Brooks
Women with a hypertensive disorder of pregnancy are at increased risk of developing dementia later in life, new research suggests.
Results from an 80-year retrospective cohort study of more than 56,000 women showed that, after adjusting for relevant co-factors, participants with a history of preeclampsia/eclampsia had a 1.38 times higher risk for all-cause dementia and a 1.58 times higher risk for vascular dementia than their peers with no history of HDP.
Further, women with a history of gestational hypertension had a 1.36 times higher risk for dementia overall and a 2.75 higher risk for vascular dementia vs those without a history of HDP.
“Health systems should ensure that women who experience HDP or other pregnancy complications should receive optimal primary and secondary preventive care for improved health across the lifespan,” co-investigator Karen Schliep, PhD, University of Utah Health, Salt Lake City, told Medscape Medical News.
She reported the findings at the Alzheimer’s Association International Conference 2022.
Impact Of Sex And Gender During Development: Setting The Stage
Examples of early and developmental sex differences come from the large Philadelphia Neurodevelopmental Cohort in which individuals ages 8 to 22 years underwent brain imaging.28 The basic physiologic process of cerebral perfusion is critical for brain metabolism and is diminished in numerous neurological disorders. This differs in magnitude and direction between males and females across development.29–31 Again, in the Philadelphia Neurodevelopmental Cohort, amygdala volume increased significantly in adolescent boys, whereas hippocampal volume increased and thinning of cortical gray matter occurred faster in girls.32 These sex differences are crucial to consider when interpreting brain-imaging outcomes in normally developing individuals, as well as in those with neuropsychiatric and cognitive disorders. Sex differences in brain development serve as the proverbial stage on which medical conditions and other risk factors associated with dementia act to increase or reveal vulnerability to pathological cognitive aging.
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