Five Advance Warnings of Multiple Sclerosis
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Five Advance Warnings of Multiple Sclerosis
First things first, a quick check-in with regard to how much you know about multiple sclerosis (MS):
- Do you know what causes it?
- Do you know how it happens?
- Do you know how it can be fixed?
If your answer to the above questions is “no”, then take solace in the fact that modern science doesn’t know either.
What we do know is that it’s an autoimmune condition, and that it results in the degradation of myelin, the “insulator” of nerves, in the central nervous system.
- How exactly this is brought about remains unclear, though there are several leading hypotheses including autoimmune attack of myelin itself, or disruption to the production of myelin.
- Treatments look to reduce/mitigate inflammation, and/or treat other symptoms (which are many and various) on an as-needed basis.
If you’re wondering about the prognosis after diagnosis, the scientific consensus on that is also “we don’t know”:
Read: Personalized medicine in multiple sclerosis: hope or reality?
this paper, like every other one we considered putting in that spot, concludes with basically begging for research to be done to identify biomarkers in a useful fashion that could help classify many distinct forms of MS, rather than the current “you have MS, but who knows what that will mean for you personally because it’s so varied” approach.
The Five Advance Warning Signs
Something we do know! First, we’ll quote directly the researchers’ conclusion:
❝We identified 5 health conditions associated with subsequent MS diagnosis, which may be considered not only prodromal but also early-stage symptoms.
However, these health conditions overlap with prodrome of two other autoimmune diseases, hence they lack specificity to MS.❞
So, these things are a warning, five alarm bells, but not necessarily diagnostic criteria.
Without further ado, the five things are:
- depression
- sexual disorders
- constipation
- cystitis
- urinary tract infections
❝This association was sufficiently robust at the statistical level for us to state that these are early clinical warning signs, probably related to damage to the nervous system, in patients who will later be diagnosed with multiple sclerosis.
The overrepresentation of these symptoms persisted and even increased over the five years after diagnosis.❞
Read the paper for yourself:
Hot off the press! Published only yesterday!
Want to know more about MS?
Here’s a very comprehensive guide:
National clinical guideline for diagnosis and management of multiple sclerosis
Take care!
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How they did it: STAT reporters expose how ailing seniors suffer when Medicare Advantage plans use algorithms to deny care
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In a call with a long-time source, what stood out most to STAT reporters Bob Herman and Casey Ross was just how viscerally frustrated and angry the source was about an algorithm used by insurance companies to decide how long patients should stay in a nursing home or rehab facility before being sent home.
The STAT stories had a far-reaching impact:
- The U.S. Senate Committee on Homeland Security and Government Affairs took a rare step of launching a formal investigation into the use of algorithms by the country’s three largest Medicare Advantage insurers.
- Thirty-two House members urged the Centers for Medicare and Medicaid Services to increase the oversight of algorithms that health insurers use to make coverage decisions.
- In a rare step, CMS launched its own investigation into UnitedHealth. It also stiffened its regulations on the use of proprietary algorithms and introduced plans to audit denials across Medicare Advantage plans in 2024.
- Based on STAT’s reporting, Medicare Advantage beneficiaries filed two class-action lawsuits against UnitedHealth and its NaviHealth subsidiary, the maker of the algorithm, and against Humana, another major health insurance company that was also using the algorithm.
- Amid scrutiny, UnitedHealth renamed NaviHealth.
The companies never allowed an on-the-record interview with their executives, but they acknowledged that STAT’s reporting was true, according to the news organization.
Ross and Herman spoke with The Journalist’s Resource about their project and shared the following eight tips.
1. Search public comments on proposed federal rules to find sources.
Herman and Ross knew that the Centers for Medicare and Medicaid Services had put out a request for public comments, asking stakeholders within the Medicare Advantage industry how the system could improve.
There are two main ways to get Medicare coverage: original Medicare, which is a fee-for-service health plan, and Medicare Advantage, which is a type of Medicare health plan offered by private insurance companies that contract with Medicare. Medicare Advantage plans have increasingly become popular in recent years.
Under the Social Security Act, the public has the opportunity to submit comments on Medicare’s proposed national coverage determinations. CMS uses public comments to inform its proposed and final decisions. It responds in detail to all public comments when issuing a final decision.
The reporters began combing through hundreds of public comments attached to a proposed Medicare Advantage rule that was undergoing federal review. NaviHealth, the UnitedHealth subsidiary and the maker of the algorithm, came up in many of the comments, which include the submitters’ information.
“These are screaming all-caps comments to federal regulators about YOU NEED TO SOMETHING ABOUT THIS BECAUSE IT’S DISGUSTING,” Ross says.
“The federal government is proposing rules and regulations all the time,” adds Herman, STAT’s business of health care reporter. “If someone’s going to take the time and effort to comment on them, they must have at least some knowledge of what’s going on. It’s just a great tool for any journalist to use to figure out more and who to contact.”
The reporters also found several attorneys who had complained in the comments. They began reaching out to them, eventually gaining access to confidential documents and intermediaries who put them in touch with patients to show the human impact of the algorithm.
2. Harness the power of the reader submission box.
At the suggestion of an editor, the reporters added a reader submission box at the bottom of their first story, asking them to share their own experiences with Medicare Advantage denials.
The floodgates opened. Hundreds of submissions arrived.
By the end of their first story, Herman and Ross had confidential records and some patients, but they had no internal sources in the companies they were investigating, including Navihealth. The submission box led them to their first internal source.
(Screenshot of STAT’s submission box.) The journalists also combed through LinkedIn and reached out to former and current employees, but the response rate was much lower than what they received via the submission box.
The submission box “is just right there,” Herman says. “People who would want to reach out to us can do it right then and there after they read the story and it’s fresh in their minds.”
3. Mine podcasts relevant to your story.
The reporters weren’t sure if they could get interviews with some of the key figures in the story, including Tom Scully, the former head of the Centers for Medicare and Medicaid Services who drew up the initial plans for NaviHealth years before UnitedHealth acquired it.
But Herman and another colleague had written previously about Scully’s private equity firm and they had found a podcast where he talked about his work. So Herman went back to the podcast — where he discovered Scully had also discussed NaviHealth.
The reporters also used the podcast to get Scully on the phone for an interview.
“So we knew we had a good jumping off point there to be like, ‘OK, you’ve talked about NaviHealth on a podcast, let’s talk about this,’” Herman says. “I think that helped make him more willing to speak with us.”
4. When covering AI initiatives, proceed with caution.
“A source of mine once said to me, ‘AI is not magic,’” Ross says. “People need to just ask questions about it because AI has this aura about it that it’s objective, that it’s accurate, that it’s unquestionable, that it never fails. And that is not true.”
AI is not a neutral, objective machine, Ross says. “It’s based on data that’s fed into it and people need to ask questions about that data.”
He suggests several questions to ask about the data behind AI tools:
- Where does the data come from?
- Who does it represent?
- How is this tool being applied?
- Do the people to whom the tool is being applied match the data on which it was trained? “If racial groups or genders or age of economic situations are not adequately represented in the training set, then there can be an awful lot of bias in the output of the tool and how it’s applied,” Ross says.
- How is the tool applied within the institution? Are people being forced to forsake their judgment and their own ability to do their jobs to follow the algorithm?
5. Localize the story.
More than half of all Medicare beneficiaries have Medicare Advantage and there’s a high likelihood that there are multiple Medicare Advantage plans in every county across the nation.
“So it’s worth looking to see how Medicare Advantage plans are growing in your area,” Herman says.
Finding out about AI use will most likely rely on shoe-leather reporting of speaking with providers, nursing homes and rehab facilities, attorneys and patients in your community, he says. Another source is home health agencies, which may be caring for patients who were kicked out of nursing homes and rehab facilities too soon because of a decision by an algorithm.
The anecdote that opens their first story involves a small regional health insurer in Wisconsin, which was using NaviHealth and a contractor to manage post-acute care services, Ross says.
“It’s happening to people in small communities who have no idea that this insurer they’ve signed up with is using this tool made by this other company that operates nationally,” Ross says.
There are also plenty of other companies like NaviHealth that are being used by Medicare Advantage plans, Herman says. “So it’s understanding which Medicare Advantage plans are being sold in your area and then which post-acute management companies they’re using,” he adds.
Some regional insurers have online documents that show which contractors they use to evaluate post-acute care services.
6. Get familiar with Medicare’s appeals databases
Medicare beneficiaries can contest Medicare Advantage denials through a five-stage process, which can last months to years. The appeals can be filed via the Office of Medicare Hearings and Appeals.
“Between 2020 and 2022, the number of appeals filed to contest Medicare Advantage denials shot up 58%, with nearly 150,000 requests to review a denial filed in 2022, according to a federal database,” Ross and Herman write in their first story. “Federal records show most denials for skilled nursing care are eventually overturned, either by the plan itself or an independent body that adjudicates Medicare appeals.”
There are several sources to find appeals data. Be mindful that the cases themselves are not public to protect patient privacy, but you can find the number of appeals filed and the rationale for decisions.
CMS has two quality improvement organizations, or QIOs, Livanta and Kepro, which are required to file free, publicly-available annual reports, about the cases they handle, Ross says.
Another company, Maximus, a Quality Improvement Contractor, also files reports on prior authorization cases it adjudicates for Medicare. The free annual reports include data on raw numbers of cases and basic information about the percentage denials either overturned or upheld on appeal, Ross explains.
CMS also maintains its own database on appeals for Medicare Part C (Medicare Advantage plans) and Part D, which covers prescription drugs, although the data is not complete, Ross explains.
7. Give your editor regular updates.
“Sprinkle the breadcrumbs in front of your editors,” Ross says.
“If you wrap your editors in the process, you’re more likely to be able to get to the end of [the story] before they say, ‘That’s it! Give me your copy,’” Ross says.
8. Get that first story out.
“You don’t have to know everything before you write that first story,” Ross says. “Because with that first story, if it has credibility and it resonates with people, sources will come forward and sources will continue to come forward.”
Read the stories
Denied by AI: How Medicare Advantage plans use algorithms to cut off care for seniors in need
UnitedHealth pushed employees to follow an algorithm to cut off Medicare patients’ rehab care
UnitedHealth used secret rules to restrict rehab care for seriously ill Medicare Advantage patients
This article first appeared on The Journalist’s Resource and is republished here under a Creative Commons license.
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Three Critical Kitchen Prescriptions
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Three Critical Kitchen Prescriptions
This is Dr. Saliha Mahmood-Ahmed. She’s a medical doctor—specifically, a gastroenterologist. She’s also a chef, and winner of the BBC’s MasterChef competition. So, from her gastroenterology day-job and her culinary calling, she has some expert insights to share on eating well!
❝Food and medicine are inextricably linked to one another, and it is an honour to be a doctor who specialises in digestive health and can both cook, and teach others to cook❞
~ Dr. Saliha Mahmood-Ahmed, after winning MasterChef and being asked if she’d quit medicine to be a full-time chef
Dr. Mahmood-Ahmed’s 3 “Kitchen Prescriptions”
They are:
- Cook, cook, cook
- Feed your gut bugs
- Do not diet
Let’s take a look at each of those…
Cook, cook, cook
We’re the only species on Earth that cooks food. An easy knee-jerk response might be to think maybe we shouldn’t, then, but… We’ve been doing it for at least 30,000 years, which is about 1,500 generations, while a mere 100 generations is generally sufficient for small evolutionary changes. So, we’ve evolved this way now.
More importantly in this context: we, ourselves, should cook our own food, at least per household.
Not ready meals; we haven’t evolved for those (yet! Give it another few hundred generations maybe)
Feed your gut bugs
The friendly ones. Enjoy prebiotics, probiotics, and plenty of fiber—and then be mindful of what else you do or don’t eat. Feeding the friendly bacteria while starving the unfriendly ones may seem like a tricky task, but it actually can be quite easily understood and implemented. We did a main feature about this a few weeks ago:
Making Friends With Your Gut (You Can Thank Us Later)
Do not diet
Dr. Mahmood-Ahmed is a strong critic of calorie-counting as a weight-loss strategy:
Rather than focusing on the number of calories consumed, try focusing on introducing enough variety of food into your daily diet, and on fostering good microbial diversity within your gut.
It’s a conceptual shift from restrictive weight loss, to prescriptive adding of things to one’s diet, with fostering diversity of microbiota as a top priority.
This, too, she recommends be undertaken gently, though—making small, piecemeal, but sustainable improvements. Nobody can reasonably incorporate, say, 30 new fruits and vegetables into one’s diet in a week; it’s unrealistic, and more importantly, it’s unsustainable.
Instead, consider just adding one new fruit or vegetable per shopping trip!
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No, taking drugs like Ozempic isn’t ‘cheating’ at weight loss or the ‘easy way out’
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Hundreds of thousands of people worldwide are taking drugs like Ozempic to lose weight. But what do we actually know about them? This month, The Conversation’s experts explore their rise, impact and potential consequences.
Obesity medication that is effective has been a long time coming. Enter semaglutide (sold as Ozempic and Wegovy), which is helping people improve weight-related health, including lowering the risk of a having a heart attack or stroke, while also silencing “food noise”.
As demand for semaglutide increases, so are claims that taking it is “cheating” at weight loss or the “easy way out”.
We don’t tell people who need statin medication to treat high cholesterol or drugs to manage high blood pressure they’re cheating or taking the easy way out.
Nor should we shame people taking semaglutide. It’s a drug used to treat diabetes and obesity which needs to be taken long term and comes with risks and side effects, as well as benefits. When prescribed for obesity, it’s given alongside advice about diet and exercise.
How does it work?
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA). This means it makes your body’s own glucagon-like peptide-1 hormone, called GLP-1 for short, work better.
GLP-1 gets secreted by cells in your gut when it detects increased nutrient levels after eating. This stimulates insulin production, which lowers blood sugars.
GLP-1 also slows gastric emptying, which makes you feel full, and reduces hunger and feelings of reward after eating.
GLP-1 receptor agonist (GLP-1RA) medications like Ozempic help the body’s own GLP-1 work better by mimicking and extending its action.
Some studies have found less GLP-1 gets released after meals in adults with obesity or type 2 diabetes mellitus compared to adults with normal glucose tolerance. So having less GLP-1 circulating in your blood means you don’t feel as full after eating and get hungry again sooner compared to people who produce more.
GLP-1 has a very short half-life of about two minutes. So GLP-1RA medications were designed to have a very long half-life of about seven days. That’s why semaglutide is given as a weekly injection.
What can users expect? What does the research say?
Higher doses of semaglutide are prescribed to treat obesity compared to type 2 diabetes management (up to 2.4mg versus 2.0mg weekly).
A large group of randomised controlled trials, called STEP trials, all tested weekly 2.4mg semaglutide injections versus different interventions or placebo drugs.
Trials lasting 1.3–2 years consistently found weekly 2.4 mg semaglutide injections led to 6–12% greater weight loss compared to placebo or alternative interventions. The average weight change depended on how long medication treatment lasted and length of follow-up.
Higher doses of semaglutide are prescribed for obesity than for type 2 diabetes. fcm82/Shutterstock Weight reduction due to semaglutide also leads to a reduction in systolic and diastolic blood pressure of about 4.8 mmHg and 2.5 mmHg respectively, a reduction in triglyceride levels (a type of blood fat) and improved physical function.
Another recent trial in adults with pre-existing heart disease and obesity, but without type 2 diabetes, found adults receiving weekly 2.4mg semaglutide injections had a 20% lower risk of specific cardiovascular events, including having a non-fatal heart attack, a stroke or dying from cardiovascular disease, after three years follow-up.
Who is eligible for semaglutide?
Australia’s regulator, the Therapeutic Goods Administration (TGA), has approved semaglutide, sold as Ozempic, for treating type 2 diabetes.
However, due to shortages, the TGA had advised doctors not to start new Ozempic prescriptions for “off-label use” such as obesity treatment and the Pharmaceutical Benefits Scheme doesn’t currently subsidise off-label use.
The TGA has approved Wegovy to treat obesity but it’s not currently available in Australia.
When it’s available, doctors will be able to prescribe semaglutide to treat obesity in conjunction with lifestyle interventions (including diet, physical activity and psychological support) in adults with obesity (a BMI of 30 or above) or those with a BMI of 27 or above who also have weight-related medical complications.
What else do you need to do during Ozempic treatment?
Checking details of the STEP trial intervention components, it’s clear participants invested a lot of time and effort. In addition to taking medication, people had brief lifestyle counselling sessions with dietitians or other health professionals every four weeks as a minimum in most trials.
Support sessions were designed to help people stick with consuming 2,000 kilojoules (500 calories) less daily compared to their energy needs, and performing 150 minutes of moderate-to-vigorous physical activity, like brisk walking, dancing and gardening each week.
STEP trials varied in other components, with follow-up time periods varying from 68 to 104 weeks. The aim of these trials was to show the effect of adding the medication on top of other lifestyle counselling.
Trial participants also exercised for 150 minutes a week. Elena Nichizhenova/Shutterstock A review of obesity medication trials found people reported they needed less cognitive behaviour training to help them stick with the reduced energy intake. This is one aspect where drug treatment may make adherence a little easier. Not feeling as hungry and having environmental food cues “switched off” may mean less support is required for goal-setting, self-monitoring food intake and avoiding things that trigger eating.
But what are the side effects?
Semaglutide’s side-effects include nausea, diarrhoea, vomiting, constipation, indigestion and abdominal pain.
In one study these led to discontinuation of medication in 6% of people, but interestingly also in 3% of people taking placebos.
More severe side-effects included gallbladder disease, acute pancreatitis, hypoglycaemia, acute kidney disease and injection site reactions.
To reduce risk or severity of side-effects, medication doses are increased very slowly over months. Once the full dose and response are achieved, research indicates you need to take it long term.
Given this long-term commitment, and associated high out-of-pocket cost of medication, when it comes to taking semaglutide to treat obesity, there is no way it can be considered “cheating”.
Read the other articles in The Conversation’s Ozempic series here.
Clare Collins, Laureate Professor in Nutrition and Dietetics, University of Newcastle
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Butternut Squash vs Pumpkin – Which is Healthier?
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Our Verdict
When comparing butternut squash to pumpkin, we picked the butternut squash.
Why?
Both are great! But the butternut squash manages a moderate win in most categories.
In terms of macros, butternut squash has more of everything except water. Most notably, it has more protein and more fiber. Yes, more carbs too, but the fiber content means that it also has the lower glycemic index, by quite a bit.
When it comes to vitamins, pumpkin does have a little more of vitamin B1 and a lot more of vitamin E, while butternut squash has more of vitamins B3, B5, B9, C, K, and choline. They’re about equal in the other vitamins they both contain. A fair win for butternut squash.
In the category of minerals, butternut squash has more calcium, magnesium, manganese, and selenium, while pumpkin has more copper, iron, and phosphorus. They’re about equal in potassium and zinc. A marginal win for butternut squash.
Adding up the strong win, the fair win, and the marginal win, makes for an easy overall win for butternut squash!
Want to learn more?
You might like to read:
Superfood-Stuffed Squash Recipe
Take care!
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What is mitochondrial donation? And how might it help people have a healthy baby one day?
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Mitochondria are tiny structures in cells that convert the food we eat into the energy our cells need to function.
Mitochondrial disease (or mito for short) is a group of conditions that affect this ability to generate the energy organs require to work properly. There are many different forms of mito and depending on the form, it can disrupt one or more organs and can cause organ failure.
There is no cure for mito. But an IVF procedure called mitochondrial donation now offers hope to families affected by some forms of mito that they can have genetically related children free from mito.
After a law to allow mitochondrial donation in Australia was passed in 2022, scientists are now preparing for a clinical trial to see if mitochondrial donation is safe and works.
Jonathan Borba/Pexels What is mitochondrial disease?
There are two types of mitochondrial disease.
One is caused by faulty genes in the nuclear DNA, the DNA we inherit from both our parents and which makes us who we are.
The other is caused by faulty genes in the mitochondria’s own DNA. Mito caused by faulty mitochondrial DNA is passed down through the mother. But the risk of disease is unpredictable, so a mother who is only mildly affected can have a child who develops serious disease symptoms.
Mitochondrial disease is the most common inherited metabolic condition affecting one in 5,000 people.
Some people have mild symptoms that progress slowly, while others have severe symptoms that progress rapidly. Mito can affect any organ, but organs that need a lot of energy such as brain, muscle and heart are more often affected than other organs.
Mito that manifests in childhood often involves multiple organs, progresses rapidly, and has poor outcomes. Of all babies born each year in Australia, around 60 will develop life-threatening mitochondrial disease.
What is mitochondrial donation?
Mitochondrial donation is an experimental IVF-based technique that offers people who carry faulty mitochondrial DNA the potential to have genetically related children without passing on the faulty DNA.
It involves removing the nuclear DNA from the egg of someone who carries faulty mitochondrial DNA and inserting it into a healthy egg donated by someone not affected by mito, which has had its nuclear DNA removed.
The donor egg (in blue) has had its nuclear DNA removed. Author provided The resulting egg has the nuclear DNA of the intending parent and functioning mitochondria from the donor. Sperm is then added and this allows the transmission of both intending parents’ nuclear DNA to the child.
A child born after mitochondrial donation will have genetic material from the three parties involved: nuclear DNA from the intending parents and mitochondrial DNA from the egg donor. As a result the child will likely have a reduced risk of mito, or no risk at all.
The procedure removes the faulty DNA to reduce the chance of it passing on to the baby. Josh Willink/Pexels This highly technical procedure requires specially trained scientists and sophisticated equipment. It also requires both the person with mito and the egg donor to have hormone injections to stimulate the ovaries to produce multiple eggs. The eggs are then retrieved in an ultrasound-guided surgical procedure.
Mitochondrial donation has been pioneered in the United Kingdom where a handful of babies have been born as a result. To date there have been no reports about whether they are free of mito.
Maeve’s Law
After three years of public consultation The Mitochondrial Donation Law Reform (Maeve’s Law) Bill 2021 was passed in the Australian Senate in 2022, making mitochondrial donation legal in a research and clinical trial setting.
Maeve’s law stipulates strict conditions including that clinics need a special licence to perform mitochondrial donation.
To make sure mitochondrial donation works and is safe before it’s introduced into Australian clinical practice, the law also specifies that initial licences will be issued for pre-clinical and clinical trial research and training.
We’re expecting one such licence to be issued for the mitoHOPE (Healthy Outcomes Pilot and Evaluation) program, which we are part of, to perfect the technique and conduct a clinical trial to make sure mitochondrial donation is safe and effective.
Before starting the trial, a preclinical research and training program will ensure embryologists are trained in “real-life” clinical conditions and existing mitochondrial donation techniques are refined and improved. To do this, many human eggs are needed.
The need for donor eggs
One of the challenges with mitochondrial donation is sourcing eggs. For the preclinical research and training program, frozen eggs can be used, but for the clinical trial “fresh” eggs will be needed.
One possible source of frozen eggs is from people who have stored eggs they don’t intend to use.
A recent study looked at data on the outcomes of eggs stored at a Melbourne clinic from 2012 to 2021. Over the ten-year period, 1,132 eggs from 128 patients were discarded. No eggs were donated to research because the clinics where the eggs were stored did not conduct research requiring donor eggs.
However, research shows that among people with stored eggs, the number one choice for what to do with eggs they don’t need is to donate them to research.
This offers hope that, given the opportunity, those who have eggs stored that they don’t intend to use might be willing to donate them to mitochondrial donation preclinical research.
As for the “fresh” eggs needed in the future clinical trial, this will require individuals to volunteer to have their ovaries stimulated and eggs retrieved to give those people impacted by mito a chance to have a healthy baby. Egg donors may be people who are friends or relatives of those who enter the trial, or it might be people who don’t know someone affected by mito but would like to help them conceive.
At this stage, the aim is to begin enrolling participants in the clinical trial in the next 12 to 18 months. However this may change depending on when the required licences and ethics approvals are granted.
Karin Hammarberg, Senior Research Fellow, Global and Women’s Health, School of Public Health & Preventive Medicine, Monash University; Catherine Mills, Professor of Bioethics, Monash University; Mary Herbert, Professor, Anatomy & Developmental Biology, Monash University, and Molly Johnston, Research fellow, Monash Bioethics Centre, Monash University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Alzheimer’s Sex Differences May Not Be What They Appear
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Alzheimer’s Sex Differences May Not Be What They Appear
Women get Alzheimer’s at nearly twice the rate than men do, and deteriorate more rapidly after onset, too.
So… Why?
There are many potential things to look at, but four stand out for quick analysis:
- Chromosomes: women usually have XX chromosomes, to men’s usual XY. There are outliers to both groups, people with non-standard combinations of chromosomes, but not commonly enough to throw out the stats.
- Hormones: women usually have high estrogen and low testosterone, compared to men. Again there are outliers and this is a huge oversimplification that doesn’t even look at other sex hormones, but broadly speaking (which sounds vague, but is actually what is represented in epidemiological studies), it will be so.
- Anatomy: humans have some obvious sexual dimorphism (again, there are outliers, but again, not enough to throw out the stats); this seems least likely to be relevant (Alzheimer’s is probably not stored in the breasts, for examples), though average body composition (per muscle:fat ratio) could admittedly be a factor.
- Social/lifestyle: once again, #NotAllWomen etc, but broadly speaking, women and men often tend towards different social roles in some ways, and as we know, of course lifestyle can play a part in disease pathogenesis.
As a quick aside before we continue, if you’re curious about those outliers, then a wiki-walk into the fascinating world of intersex conditions, for example, could start here. But by and large, this won’t affect most people.
So… Which parts matter?
Back in 2018, Dr. Maria Teresa Ferretti et al. kicked up some rocks in this regard, looking not just at genes (as much research has focussed on) or amyloid-β (again, well-studied) but also at phenotypes and metabolic and social factors—bearing in mind that all three of those are heavily influenced by hormones. Noting, for example, that (we’ll quote directly here):
- Men and women with Alzheimer disease (AD) exhibit different cognitive and psychiatric symptoms, and women show faster cognitive decline after diagnosis of mild cognitive impairment (MCI) or AD dementia.
- Brain atrophy rates and patterns differ along the AD continuum between the sexes; in MCI, brain atrophy is faster in women than in men.
- The prevalence and effects of cerebrovascular, metabolic and socio-economic risk factors for AD are different between men and women.
See: Sex differences in Alzheimer disease—the gateway to precision medicine
So, have scientists controlled for each of those factors?
Mostly not! But they have found clues, anyway, while noting the limitations of the previous way of conducting studies. For example:
❝Women are more likely to develop Alzheimer’s disease and experience faster cognitive decline compared to their male counterparts. These sex differences should be accounted for when designing medications and conducting clinical trials❞
~ Dr. Feixiong Cheng
Read: Research finds sex differences in immune response and metabolism drive Alzheimer’s disease
Did you spot the clue?
It was “differences in immune response and metabolism”. These things are both influenced by (not outright regulated by, but strongly influenced by) sex hormones.
❝As [hormonal] sex influences both the immune system and metabolic process, our study aimed to identify how all of these individual factors influence one another to contribute to Alzheimer’s disease❞
~ Dr. Justin Lathia
Ignoring for a moment progesterone’s role in metabolism, estrogen is an immunostimulant and testosterone is an immunosuppressant. These thus both also have an effect in inflammation, which yes, includes neuroinflammation.
But wait a minute, shouldn’t that mean that women are more protected, not less?
It should! Except… Alzheimer’s is an age-related disease, and in the age-bracket that generally gets Alzheimer’s (again, there are outliers), menopause has been done and dusted for quite a while.
Which means, and this is critical: post-menopausal women not on HRT are essentially left without the immune boost usually directed by estrogen, while men of the same age will be ticking over with their physiology that (unlike that of the aforementioned women) was already adapted to function with negligible estrogen.
Specifically:
❝The metabolic consequences of estrogen decline during menopause accelerate neuropathology in women❞
~ Dr. Rasha Saleh
Critical idea to take away from all this:
Alzheimer’s research is going to be misleading if it doesn’t take into account sex differences, and not just that, but also specifically age-relevant sex differences—because that can flip the narrative. If we don’t take age into account, we could be left thinking estrogen is to blame, when in fact, it appears to be the opposite.
In the meantime, if you’re a woman of a certain age, you might talk with a doctor about whether HRT could be beneficial for you, if you haven’t already:
❝Women at genetic risk for AD (carrying at least one APOE e4 allele) seem to be particularly benefiting from MHT❞
(MHT = Menopausal Hormone Therapy; also commonly called HRT, which is the umbrella term for Hormone Replacement Therapies in general)
~ Dr. Herman Depypere
Source study: Menopause hormone therapy significantly alters pathophysiological biomarkers of Alzheimer’s disease
Pop-sci press release version: HRT could ward off Alzheimer’s among at-risk women
Take care!
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