Tag Archive for: Alzheimer’s Disease

Brain Health in Pregnancy, Menopause, and Beyond – Is There a Link with Alzheimer’s disease?

Interviewee: Alesia V. Prakapenka, Assistant Professor, Biomedical Sciences, College of Graduate Studies, Midwestern University  Authors/Editors: Romina Garcia de leon, Shayda Swann (Blog Co-coordinators)

Published: January 5, 2024

 

Could you tell us more about the work you do in women’s health?

 

In my lab, we use animal models to understand how hormones impact brain and behavioral health within females and we take on a lifespan approach. We recently were awarded a grant from the Alzheimer’s Association to investigate the relationship between pregnancy, age, and menopause on healthy aging and Alzheimer’s disease progression in female rodent models. We’re very excited to get that work started. Primary outcomes include both short-term and long-term memory measures, as well as evaluation of memory types that engage different brain regions, including hippocampus, frontal cortex, and striatum. We’re also interested in anxiety-like and depressive-like behaviors as these are modulated by hormones and are associated with Alzheimer’s disease. 

 

How did you become involved in this field?

 

I’m fascinated by how learning, memory, and the brain works in general. When I was in high school, I took a psychology class and one of the units was on the brain. That sparked my interest, and I really wanted to learn more about what we know and what we don’t know about the brain. As an undergraduate, I got involved in research in a lab that used animal models to study learning and memory, and one interesting aspect of it was that the lab only worked with male animals. That got me thinking and looking more into the research on how learning and memory works in males versus females. To me, it seemed like there was a gap in understanding female learning, memory, and brain functions compared to males. So, for graduate school, I pursued research that focused specifically on female learning and memory with my co-mentors, Drs. Heather Bimonte-Nelson and Rachael Sirianni. Specifically, I worked on developing strategies to target the delivery of hormones, such as estrogens, to the brain to optimize their cognitive effects in females. My graduate research led to many more questions than answers regarding hormones and female health, which I am excited to continue to research. 

 

What does a typical day in your field look like? 

 

If we’re working with the animals, the timelines are planned out months in advance. With this new project looking at pregnancy and Alzheimer’s disease, for example, we have a schedule set for 2-3 years because we are working with animals throughout their lifespan. Some days, we’re administering treatments, checking in on the health of animals, or testing behavior and memory tasks. And then other days we’re getting to work with the tissue – process it, tag it with antibodies, and then visualize it. And then other days we’re on a computer looking at lots and lots of spreadsheets, analyzing the data and putting it together to understand and share what we find.

 

Are there any interesting findings from your work that you’d like to highlight?

 

My lab is in its second year, so our data collection is currently very fresh and ongoing. For example, as we establish our behavior tasks and protocols in the lab, we are finding that dose-dependent effects of 17beta-estradiol on spontaneous alternation behaviors are modulated by specific task parameters in female rats. And although we do not yet have findings from our lab for our recently funded work, I’d love to highlight valuable findings from other labs’ in the field that informed and sparked this research direction. There are multiple findings, for example, showing that pregnancy is neuroprotective and beneficial for female brain health. There’s also some evidence to suggest that pregnancy can be associated with increased Alzheimer’s disease risk. So, we aim to investigate factors, such as age and menopause type, that may help explain the disparate effects of pregnancy on healthy aging and Alzheimer’s disease pathogenesis.

 

What impact do you hope to see with your work?

 

The impact I hope to see with my work is rooted in student mentorship. Majority of students that I work with are either on a pre-healthcare career path or in their first or second year of medical or dental school. My approach is to mentor students, most of whom will be future healthcare professionals and inevitably working with the female population, to appreciate the complexity of female health and embrace it. I hope to help them understand the research on female health, critically analyze it, and appreciate it so that when they are forming that medical plan for an individual, they can be comfortable addressing female-specific health aspects.

 

Look out for Dr. Prakapenka’s upcoming work funded by the Alzheimer’s Association, through the Sex and Gender in Alzheimer’s Award, titled ‘Alzheimer’s disease pathogenesis in mothers: a role for age and menopause’.

Menopause Series Part 2: All About Reproductive Hormones

Authors: Katrine Yare, PhD, Medical & Cognitive Research Unit (MCRU), Austin Health, Melbourne, Australia | Editors:  Romina Garcia de leon and Shayda Swann

Published: October 20th, 2023

*Throughout this series, we want to acknowledge that not all women will experience menopause, and not all folks who experience menopause identify as women. We understand that different terminology will suit different folks. We hope this information is helpful to folks of diverse genders and identities*

I’m a mum, a researcher, and I study the effects of the primary reproductive hormones, 17-beta oestradiol (also called E2) and cyclical progesterone (P4) on sporadic Alzheimer’s disease (AD) in women.

Before I progress, Alzheimer’s disease (also called AD) is more prevalent in women, with two-thirds of those exhibiting symptoms of AD being post-menopausal women. My research focuses on an earlier phase of the disease, called the preclinical AD stage (before a person develops symptoms). This can develop years earlier.

A little background on women’s hormones

Understanding our bodies and how our hormones work can empower us as women to make informed choices when discussing our menopausal concerns with our health professionals. Knowledge really is power.

There are three primary estrogens in women:

  1. 17-beta-oestradiol (E2) also called oestradiol or estradiol. It is the most potent estrogen and works together with a cyclical hormone, progesterone (P4), during the reproductive phase of women’s lives.
     
  2. Oestrone (E1) also called estrone. This is the menopausal hormone, which is much less potent than E2.
     
  3. Oestriol (E3) also called estriol. E3 is a pregnancy estrogen and is the lowest potency estrogen. It works together with P4 (and other hormones), to protect the developing baby and to maintain pregnancy.

For this blog, I will concentrate on the hormones E2 and cyclical P4, which are essential in maintaining health during the reproductive phase of women’s lives.

The actions of the primary reproductive hormones, E2 and cyclical P4, are not confined to reproductive functions such as the menstrual cycle and pregnancy but play a significant beneficial role in many bodily systems (e.g., central nervous system, cardiovascular system, gastrointestinal tract, urogenital system, muscles, bone, skin, etc.), as well as modulating numerous metabolic processes and neurotransmitters.

When the levels of these hormones fluctuate during perimenopause and drop markedly during menopause, this will impact a multitude of physiological, cellular, and metabolic processes that are modulated by these hormones. As a result, most women will be impacted by this change. Some women will choose hormone therapy (HT) to alleviate symptoms, some women choose to ride through menopause without treatment, and there are also a rare few who won’t experience any overt symptoms. With respect to the latter, even though these women don’t experience overt symptoms, they are undergoing changes on a cellular and molecular level.

As discussed in the menopause series blog 1, some symptoms women may experience due to a drop in E2 and P4 include difficulty regulating body temperature, hot flushes, night sweats, vaginal dryness, dry and itchy skin, joint pain, muscle aches and pains, digestive problems, weight gain, breast tenderness, loss of breast volume, gum changes, headaches, migraines.

E2 and P4 also modulate a number of neurotransmitters. For example, E2 is a serotonin, dopamine, and cholinergic modulator, and P4 (via its metabolites) is a potent GABA-A receptor modulator. Therefore, when the levels of these two hormones drop markedly during menopause these neurotransmitters will be impacted, and, as a consequence, most women will feel the effects. Some symptoms women may experience include anxiety, depression, restlessness, brain fog, difficulty concentrating, irritability, mood swings, dizziness, and insomnia.

Paying attention to your health and well-being as your body undergoes significant change is essential whether you choose to go on HT or not. Also, establishing a good relationship with your health professional where you can freely discuss your menopausal concerns and they can help by listening and offering options or solutions, including clearly outlining benefits and risks, is extremely important.

As a menopausal woman myself, I had a horrible time during the menopausal transition. Even though I chose HT to alleviate my symptoms, which used hormones that were molecularly the same as what our bodies produced during the reproductive phase (i.e., E2 & cyclical P4) and used a route of administration that closely approximates the way our hormones are metabolized in our bodies (this will be discussed more at length in the next blog), I am vigilant about my health.

I want you to be vigilant about your health, too.

Behind the Science: Clearing the Fog of Midlife Ovarian Removal and Cognition

Interviewee: Alana Brown, Ph.D. Candidate, University of Toronto, Authors/Editors: Romina Garcia de leon, Shayda Swann (Blog Co-coordinators).

Published: July 14th, 2023

Could you tell us about your research?

In Dr. Gillian Einstein’s Lab of Cognitive Neuroscience, Gender, and Health, my PhD work explores the relationships between ovarian hormones (e.g., 17β-estradiol) and cognition, specifically in women with breast cancer gene mutations who opt to have bilateral salpingo-oophorectomy, which is the removal of both ovaries and fallopian tubes. This surgery usually occurs for cancer prevention purposes around 10 years prior to the typical age of spontaneous/natural menopause (~51 years). Bilateral salpingo-oophorectomy results in an abrupt and early loss of ovarian hormones. Our group in Dr. Einstein’s lab is trying to understand the cognitive impact of this hormone loss, especially given that oophorectomy is associated with an increased risk of developing Alzheimer’s disease (AD) in later life.

What drove you to study women’s health research? 

There is a dearth of research examining factors contributing to cognition among middle-aged women. The spontaneous menopause transition is a time period often defined by self-reported brain fog. So, women are specifying that their memory is changing during this period. Not only is there a gap in research to try to understand this change, but this is also a unique opportunity to answer more nuanced questions about memory in a healthy population. This research gap is even wider for women with bilateral salpingo-oophorectomy.

It is really interesting that we can ask richer questions about memory by looking at an ovarian hormone shift that affects a large number of people in the world. For example, how can the memory changes associated with ovarian hormone loss be differentiated from the memory changes associated with aging? How can we use ovarian hormone-related structural and functional brain changes to answer questions about how the brain supports memory more broadly? In the realm of neuroimaging, menopause and sex-specific factors are conflated with aging and largely overlooked and disregarded. It is very common to see neuroimaging research focusing on aging by studying groups of young adults who are 35 or younger and comparing them to groups of older adults who are 65 or older. The large gap between those age groups, representing midlife, during which menopause is typically occurring, is often ignored. There is a really small percentage of research looking at female-specific outcomes during that time.

What impact do you hope to see with this work?

I hope that this work can contribute to a larger picture of precision medicine. Given that we are studying a group of women who are at increased risk for AD, there may be implications for AD biomarkers. Female-specific AD risk factors must be studied and clarified. I hope this work can contribute to a larger body of research focused on studying people and the complexities of their lives while integrating that complexity into neuroimaging. Further, I hope we know more about the functional effects of reproductive aging and/or ovarian hormone loss in the future, above and beyond the effects of aging. This is new territory for neuroimaging. Those considering bilateral salpingo-oophorectomy deserve to be fully informed and aware of what they may experience after the surgery.

Have you seen any interesting findings yet in your research? 

We are finding that oophorectomy without 17β-estradiol  replacement therapy is associated with decreased hippocampal activation, specifically while learning/encoding during a face-name pair memory paradigm that is thought to be sensitive to AD progression. The hippocampus is a brain area critical for learning/memory and is also among the first regions affected by AD. We do not see the same pattern in individuals with oophorectomy who are taking 17β-estradiol replacement therapy. It is possible that 17β-estradiol has a role in maintaining function in the hippocampus and potential markers of AD risk could be detected in midlife. 

Where can people find more about your work?

Twitter: @4alanabrown and @EinsteinLabUofT, 

Online: https://einsteinlab.ca

LinkedIn: https://www.linkedin.com/in/alana-brown-23544a111/

Check out this recent publication by Alana and the Einstein Lab on how midlife ovarian removal affects cognition!

The Gut-Brain Connection: Why Biological Sex May Matter

Author: Avril Metcalfe-Roach, PhD student, University of British Columbia | Editors: Negin Nia and Arrthy Thayaparan (Blog Coordinators) 

Published: November 12th, 2021

If you had to build your own house from scratch, what supplies would you bring to the job? High-quality building materials would certainly make the house much more durable, and having a diverse array of tools on hand will make construction much easier. 

Joe, on the other hand, brought just four zip ties and a wrench and is probably in for a tough time. If you live in a hot climate, you might consider installing air conditioning; in cold climates, good insulation and a heater will help you avoid freezing during the winter. In any case, putting love and effort into the home helps ensure that it keeps you comfortable for many years.

Similarly, the food we eat directly impacts every facet of our health. The links between diet, obesity, and cardiovascular disease are well known. However, more research indicates that dietary habits also directly impact issues like cancer, mental health, and even neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Healthy eating can also indirectly reduce disease burden by ensuring that your body has the tools it needs to heal and combat infection.

So, how do different foods actually exert these effects? 

Each food, of course, has a different nutritional profile and will provide your body with different tools. We can anticipate what tools we will need and provide them before problems arise. For example, people who menstruate require more iron in their diets, and oral contraceptive use can lower the absorption of multiple vitamins and minerals. 

Humans also have a little problem: we’re more complex than our genetics allow. While our bodies directly absorb and create many nutrients, a lot of essential nutrients are created solely by the 100 trillion bacteria living in our intestines. In exchange for some energy and a warm place to call home, these beneficial bacteria help to prevent other harmful bacteria from infecting the gut. This keeps our gut tissue working properly, and produces vitamins and other compounds that can leave the gut and promote health throughout the body. For example, certain types of fiber are broken down by bacteria into molecules that enter the bloodstream and help to reduce inflammation.

Even the ‘happy’ chemical, serotonin, is mostly produced in the gut. Like us, each type of bacteria has its own nutritional requirements that mostly revolve around fiber-rich foods such as fruits and whole grains. By eating a variety of nutrient-dense foods, we foster a gut environment full of healthy, anti-inflammatory bacteria that in turn keep us healthy. 

What type of diets are sustainable and have health benefits?

Dietary research is progressing at a staggering rate, and it can be overwhelming to stay up to date. When the research is clarified, however, certain dietary patterns emerge that are consistently linked with specific health outcomes. 

The Mediterranean diet, which promotes plant-based foods, fish, and healthy oils, while limiting red meat and other animal products, is perhaps the best-studied healthy diet in the world. It has been associated with lower rates of cardiovascular disease, obesity, glucose sensitivity and diabetes, and overall mortality.

More recently, a few studies have suggested that the Mediterranean diet may improve brain health. Neurodegenerative diseases are not yet well understood, and there are very few known factors that help to prevent them. Recognizing this, Dr. Martha Clare Morris unveiled the MIND diet in 2015, which optimizes the Mediterranean diet against cognitive decline.

What is the MIND diet and how does it benefit us?

Most food groups are conserved between the two diets; crucially, however, the MIND diet also promotes brain-healthy berries and leafy greens, while restricting pro-inflammatory sugary, fried, and processed food. These latter foods are becoming increasingly common, especially in North America; some research suggests that their overconsumption can even negate some of the health benefits normally associated with the Mediterranean diet. 

As a result, the MIND diet has since been associated with significantly reduced rates of many neurodegenerative diseases, including Alzheimer’s, cognitive decline, and general motor decline; what’s more, the strength of these associations seems to exceed those of the Mediterranean diet.

We recently investigated the MIND diet in a group of individuals with Parkinson’s disease, where we assessed their normal dietary intake and assigned a score based on how closely their intake resembled the MIND diet. Female participants had higher scores on average, indicating closer MIND diet resemblance. Participants with high scores developed Parkinson’s disease significantly later than those with low scores; unexpectedly, this association was especially strong in the female participants, where dietary habits accounted for up to 17 years’ difference in disease onset. Interestingly, the MIND diet accounted for only 10 years in men, and the Mediterranean diet accounted for 10 years with no apparent sex differences.

How do these diets work exactly?

While the complexity of these diets means that it is difficult to know exactly how they work, a sizable amount of research has zeroed in on our microscopic friends as a key factor. Brain-healthy diets help anti-inflammatory bacteria to thrive, which may help to limit inflammation in the brain. Regulation of the immune system is known to be partially sex-specific – for example, women are more prone to autoimmune disease, where the immune system attacks healthy body tissue – and these differences might impact how effective the diets are against neurodegeneration. Indeed, women make up only 1/3 of all Parkinson’s disease cases

While our findings here are only correlational, they highlight the importance of including sex as a factor in further research. With a strong enough framework, everyone can design a house that will keep them happy and healthy for a lifetime.

 

Behind the Science with Bonnie Lee

Authors: Arrthy Thayaparan and Alex Lukey (Blog Coordinators) Interviewing: Bonnie Lee, PhD Student, UBC 

Published: December 25th, 2020

At the Women’s Health Research Cluster, we strive to close the gaps in communication and knowledge between the public and scientific community. As such, our newest blog series, Behind the Science, will take a sneak peek into the world of science through a series of interviews with some amazing women’s health researchers. We hope that this series will spark interest in the general public and young students by understanding the journeys of these researchers

So we’re starting off with a BANG and introducing our very first interviewee! She is a future leader in the study of women’s health and a beloved colleague of the WHRC team. As a graduate neuroscience researcher at UBC, her work primarily looks at the impacts of motherhood and Alzheimer’s on cognition and the ageing brain. 

If that didn’t make any sense to you, then not to worry! The following interview will simplify the research, whilst also breaking down misconceptions of the research field. Without furtherado, it is our pleasure to introduce Bonnie Lee

How did you become interested in women’s health research?

So I guess I first became interested in women’s health research when, in my undergrad, I realized that none of my courses really talked about sex differences. Like how different phenomena that we’re studying may be different, or even the same in males or females. It’s kind of been ignored or glossed over.

During undergrad, I was working on a research project that looked at sex differences in the relationship between stress and neurogenesis. That’s kind of how I stumbled into the world of sex differences. Then in my fourth year, I took a course with Dr. Liisa Galea on neuroplasticity. She brought up a lot of interesting ideas about sex differences and women’s health, which really opened my mind and got me fascinated about women’s health research.

Then, of course, later on, being part of Liisa’s lab as a grad student even furthered my interest as I learned more about the intricacies and nuances of women’s health research.

Why do you think we need to focus on women’s health?

Well, I think just the woman’s lifespan is so interesting. From the menstrual cycle to pregnancy and motherhood to menopause — there is so much we have yet to learn about these life events. Even besides that, so many diseases are more prevalent or more severe in females. There’s so much we don’t know about those topics. 

We all know someone who gave birth — like your mom, for example. So the fact that we don’t know much about [women’s health], it’s just crazy. Speaking of diseases that are more prevalent in females, my research is focused on Alzheimer’s disease. It is known that females have a greater lifetime risk of Alzheimer’s disease, but more intriguing to me is the fact that pregnancy and motherhood play an interesting role in the manifestation of the disease — with earlier onset, more severe pathology in the brain, and so on, in women with previous reproductive experience. It makes me wonder, why is that? And I think it’s not just about women’s health, right? The fact that we are able to learn something about why it’s more prevalent in females will tell us more about the disease in general. We’ll know more about different treatment options. So it’s not just going to benefit women, it’s going to benefit everyone, including men.

How did you decide to research Alzheimer’s, like in the scope of all possible diseases? 

I was always interested in Alzheimer’s disease. A little personal background, I used to volunteer in a senior home where I played piano for them every weekend. I became really close to a senior who had Alzheimer’s disease. I guess that kind of put a seed in my brain and made me want to learn more about the disease.

I think a lot of people can relate because it is a really prevalent disease — many have family members or friends who might have been diagnosed with Alzheimer’s or experienced taking care of someone with Alzheimer’s disease. When I realized all the sex differences and long-term effects of pregnancy and motherhood in relation to Alzheimer’s disease, I think that’s when I really felt like this is something I want to dive deeper into and try to figure out why.

So, what drew you to neuroscience and to study the impacts on motherhood, especially?

So this goes all the way back to first year. In my first year, we had something called Imagine Day at UBC. My leader was actually a neuroscience major. I never knew that you could major in neuroscience at UBC! When I first got in, I thought “Okay, I’m going to be in science, I’m going to learn either chemistry or biology or physics.”  I was actually interested in psychology, too, though, in high school. I always wanted to learn more about the brain so after finding out there’s a major for that, it was no brainer for me [pun intended]. So I did my undergrad in neuroscience, and then the rest is history.

How would you explain your research if you were explaining it to a second-grader?

So Alzheimer’s disease is a brain disorder that impairs cognition and your brain. I am interested in looking at females who were either pregnant or not pregnant, and then how Alzheimer’s disease affects their brain and their cognition in middle age.

Do you have any early findings? Or any interesting leads yet?

Yeah, we do. But it’s a bit more complicated, so it’s not going to be for the second-grader. We found some differences that have to do with the APOE epsilon 4 (APOEe4) allele, which is a genetic risk factor for late-onset sporadic Alzheimer’s disease. 

The rats that had the genetic risk for Alzheimer’s disease made more errors in the spatial working memory task compared to healthy wildtype rats – which is what we expected to find. What’s interesting is that there were differences in search strategies in the memory task between groups of rats that had been pregnant vs never pregnant. Basically, the rats that had been pregnant before were less efficient than rats that had never been pregnant before. This shows the long-term effects that pregnancy can have on the brain, which is always exciting to see. We also found differences in neurogenesis and neuroinflammation measures between the groups. APOEe4 rats (the rats that had the genetic risk) had more neural stem cells but fewer new neurons in the brain compared to wildtypes — suggesting that perhaps their neural stem cells weren’t very active in the sense that they didn’t become new neurons, or maybe they became something else, like astrocytes or other neural stem cells. On the other hand, rats that had been pregnant saw the opposite effect: they had fewer neural stem cells but more new neurons compared to rats that had never been pregnant. This could mean that rats that had been pregnant had neural stem cells that were really active and were able to become new neurons. I won’t go into any more detail here, but if anyone has any follow-up questions or anything, they can email me anytime [bonnie_lee@psych.ubc.ca].

So, what stage of research are you in right now? 

So my first chapter, I guess, my first big experiment has been done. I am dealing with brain samples now and processing the tissue to finish up analyses of different measures. Specifically, I have been looking at measures of neurogenesis, neuroinflammation, and a little bit of tryptophan metabolomics as well. So just finishing up those analyses. I am hoping to start my next chapter in January, where we will be looking closer at sex differences this time and differences between rats with either APOEe3 or APOEe4.

What makes you excited about the future in women’s health research?

I think things like the Woman’s Health Research Cluster. The WHRC is helping diverse and multidisciplinary trainees and researchers find each other and collaborate on new projects, which is really exciting. I am looking forward to seeing what kind of research comes out of those collaborations. 

I am also really hopeful about the fact that the cluster is targeting a wide audience. We don’t just involve trainees and researchers, but also policymakers, patient partners, health practitioners … getting the public involved and making them aware that women’s health is important. I think that is a huge step and an important one.

Practicing knowledge translation in science is still new to me. But I think it’s so important because you could be doing all this work, but we need people to be aware of the work so it can be applied appropriately. And that way, your research becomes more meaningful, I think.

After talking about your journey, do you have any advice for people just starting or interested in research?

Practically speaking, I would say, do your research. Look into different topics that you might be interested in, but also different researchers and their body of work. Try talking to graduate students and early-career professors. For me, at least, talking to different people and getting their perspective has been very insightful.

Before I started, I used to think, “[research] is so boring, I would never want to do this.” But, as I started to talk to more principal investigators and graduate students, and as I started to become involved in labs as a volunteer, I began to realize what it’s really to be in research, and I began to really like it! So I would suggest talking to people, keeping an open mind, and find ways to get involved in research early on.

Is there something that people can look forward to coming from you in the future? 

I do have a chapter that should be published soon. It is a chapter on the sex differences in neurogenesis and the implications for Alzheimer’s disease, and I wrote it with another member of my lab and the research cluster, Tanvi Puri as well as Dr. Liisa Galea. Yeah, I guess other than that, just more experiments and hoping to publish more papers soon!

Alex and Arrthy (Women’s Health Blog Coordinators) would like to thank Bonnie for taking the time for this interview. To our readers: keep an eye out for more blogs and interviews! If you would like to be featured, please don’t hesitate to reach out to us at womenshealth.blog@ubc.ca!