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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What You Don’t Know Can Kill You
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Knowledge Is Power!
This is Dr. Simran Malhotra. She’s triple board-certified (in lifestyle medicine, internal medicine, and palliative care), and is also a health and wellness coach.
What does she want us to know?
Three things:
Wellness starts with your mindset
Dr. Malhotra shifted her priorities a lot during the initial and perhaps most chaotic phase of the COVID pandemic:
❝My husband, a critical care physician, was consumed in the trenches of caring for COVID patients in the ICU. I found myself knee-deep in virtual meetings with families whose loved ones were dying of severe COVID-related illnesses. Between the two of us, we saw more trauma, suffering, and death, than we could have imagined.
The COVID-19 pandemic opened my eyes to how quickly life can change our plans and reinforced the importance of being mindful of each day. Harnessing the power to make informed decisions is important, but perhaps even more important is focusing on what is in our control and taking action, even if it is the tiniest step in the direction we want to go!❞
~ Dr. Simran Malhotra
We can only make informed decisions if we have good information. That’s one of the reasons we try to share as much information as we can each day at 10almonds! But a lot will always depend on personalized information.
There are one-off (and sometimes potentially life-saving) things like health genomics:
The Real Benefit Of Genetic Testing
…but also smaller things that are informative on an ongoing basis, such as keeping track of your weight, your blood pressure, your hormones, and other metrics. You can even get fancy:
Track Your Blood Sugars For Better Personalized Health
Lifestyle is medicine
It’s often said that “food is medicine”. But also, movement is medicine. Sleep is medicine. In short, your lifestyle is the most powerful medicine that has ever existed.
Lifestyle encompasses very many things, but fortunately, there’s an “80:20 rule” in play that simplifies it a lot because if you take care of the top few things, the rest will tend to look after themselves:
These Top Few Things Make The Biggest Difference To Overall Health
Gratitude is better than fear
If we receive an unfavorable diagnosis (and let’s face it, most diagnoses are unfavorable), it might not seem like something to be grateful for.
But it is, insofar as it allows us to then take action! The information itself is what gives us our best chance of staying safe. And if that’s not possible e.g. in the worst case scenario, a terminal diagnosis, (bearing in mind that one of Dr. Malhotra’s three board certifications is in palliative care, so she sees this a lot), it at least gives us the information that allows us to make the best use of whatever remains to us.
See also: Managing Your Mortality
Which is very important!
…and/but possibly not the cheeriest note on which to end, so when you’ve read that, let’s finish today’s main feature on a happier kind of gratitude:
How To Get Your Brain On A More Positive Track (Without Toxic Positivity)
Want to hear more from Dr. Malhotra?
Showing how serious she is about how our genes do not determine our destiny and knowledge is power, here she talks about her “previvor’s journey”, as she puts it, with regard to why she decided to have preventative cancer surgery in light of discovering her BRCA1 genetic mutation:
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Burn! How To Boost Your Metabolism
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Let’s burn! Metabolic tweaks and hacks
Our metabolism is, for as long as we live, a constantly moving thing. And it’s not a monolith either; there are parts of our metabolism that can speed up or slow down independently of others.
If we talk about metabolism without clarifying context, though, this is usually about one’s “basal metabolic rate”, that is, how many calories we burn just by being alive.
Why do we want to speed it up? Might we ever want to slow it down?
We might want to slow our metabolism down in survival circumstances, but generally speaking, a faster metabolism is a better one.
Yes, even when it comes to aging. Because although metabolism comes with metabolizing oxygen (which, ironically, tends to kill us eventually, since this is a key part of cellular aging), it is still beneficial to replace cells sooner rather than later. The later we replace a given cell (ie, the longer the cell lives), the more damaged it gets, and then the copy is damaged from the start, because the damage was copied along with it. So, best to have a fast metabolism to replace cells quickly when they are young and healthy.
A quick metabolism helps the body to do this.
Most people, of course, are interested in a fast metabolism to burn off fat, but beware: if you increase your metabolism without consideration to how and when you consume calories, you will simply end up eating more to compensate.
One final quick note before we begin:
Limitations
There’s a lot we can do to change our metabolism, but there are some things that may be outside of our control. They include:
- Age—we can influence our biological age, but we cannot (yet!) halt aging, so this will happen
- Body size—and yes we can change this a bit, but we all have our own “basic frame” to work with. Someone who is 6’6” is never going to be able to have the same lower-end-of-scale body mass of someone who is 5’0”, say.
- Sex—this is about hormones, and HRT is a thing, but for example, broadly speaking, men will have faster metabolisms than women, because of hormonal differences.
- Medical conditions—often also related to other hormones, but for example someone with Type 1 Diabetes is going to have a very different relationship with their metabolism than someone without, and someone with a hypo- or hyperactive thyroid will again have a very different metabolism in a way that that lifestyle factors can’t completely compensate for.
The tips and tricks
Intermittent fasting
Intermittent fasting has been found to, amongst other things, promote healthy apoptosis and autophagy (in other words: early programmed cell death and recycling—these are good things).
It also has anti-inflammatory benefits and decreases the risk of insulin resistance. In other words, intermittent fasting boosts the metabolism while simultaneously guarding against some of the dangers of a faster metabolism (harms you’d get if you instead increased your metabolism by doing intense exercise and then eating a mountain of convenience food to compensate)
Read the science: Intermittent Fasting: Is the Wait Worth the Weight?
Read our prior article: Fasting Without Crashing? We Sort The Science From The Hype
Enjoy plenty of protein
This one won’t speed your metabolism up, so much as help it avoid slowing down as a result of fat loss.
Because of our body’s marvelous homeostatic system trying to keep our body from changing status at any given time, often when we lose fat, our body drops our metabolism to compensate, thinking we are in an ongoing survival situation and food is scarce so we’d better conserve energy (as fat). That’s a pain for would-be weight-loss dieters!
Eating protein can let our body know that we’re perfectly safe and not starving, so it will keep the metabolism ticking over nicely, without putting on fat.
Read the science: The role of protein in weight loss and maintenance
Stay hydrated
People think of drinking water as part of a weight loss program being just about filling oneself up, and that is a thing, but it also has a role to play in our metabolism. Specifically, lipolysis (the process of removing fat).
Because, we are mostly water. Not only is it the main content of our various body tissue cells, but also, of particular note, our blood (the means by which everything is transported around our body) is mostly water, too.
It’s hard for the body to keep everything ticking over like a well-oiled machine if its means of transportation is sluggish!
Check it out: Increased Hydration Can Be Associated with Weight Loss
Take a stand
That basal metabolic rate we talked about?
- If you’re lying down at rest, that’s what your metabolism will be like.
- If you’re sitting up, it’ll be a little quicker, but not much.
- If you’re standing, suddenly half your body is doing things, and you don’t even notice them because they’re just stabilizing muscles and the like, but on a cellular level, your body gets very busy.
Read all about it: Cardiometabolic impact of changing sitting, standing, and stepping in the workplace
Time to invest in a standing desk? Or a treadmill in front of the TV?
The spice of life
Capsaicin, the compound in many kinds of pepper that give them their spicy flavor, boosts the metabolism. In the words of Tremblay et al for the International Journal of Obesity:
❝[Capsaicin] stimulates the sympathoadrenal system that mediates the thermogenic and anorexigenic effects of capsaicinoids.
Capsaicinoids have been found to accentuate the impact of caloric restriction on body weight loss.
Some studies have also shown that capsinoids increase energy expenditure.
Capsaicin supplementation attenuates or even prevents the increase in hunger and decrease in fullness as well as the decrease in energy expenditure and fat oxidation, which normally result from energy restriction❞
Read for yourself: Capsaicinoids: a spicy solution to the management of obesity?
You snooze, you lose (fat)
While exercising is generally touted as the road to weight loss, and certainly regular exercise does have a part to play, doing so without good rest will have bad results.
In fact, even if you’re not exercising, if you don’t get enough sleep your metabolism will get sluggish to try to slow you down and encourage you to sleep.
So, be proactive, and make getting enough good quality sleep a priority.
Eat for metabolic health
Aside from the chilli peppers we mentioned, there are other foods associated with good metabolic health. We don’t have room to go into the science of each of them here, but here’s a well-researched, well-sourced standalone article listing some top choices:
The 12 Best Foods to Boost Your Metabolism
Enjoy!
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Coconut Milk vs Soy Milk – Which is Healthier?
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Our Verdict
When comparing coconut milk to soy milk, we picked the soy.
Why?
First, because there are many kinds of both, let’s be clear which ones we’re comparing. For both, we picked the healthiest options commonly available, which were:
- Soy milk, unsweetened, fortified
- Coconut milk, raw (liquid expressed from grated meat and water)
Macronutrients are our first consideration; coconut milk has about 3x the carbs and about 14x the fat. Now, the fats are famously healthy medium-chain triglycerides (MCTs), but still, one cup of coconut milk contains about 2.5x the recommended daily amount of saturated fat, so it’s wise to go easy on that. Coconut milk also has about 4x the fiber, but still, because the saturated fat difference, we’re calling this one a win for soy milk.
In the category of vitamins, the fortified soy milk wins. In case you’re curious: milk in general (animal or plant) is generally fortified with vitamin D (in N. America, anyway; other places may vary), and vitamin B12. In this case, the soy milk has those, plus some natural vitamins, meaning it has more of vitamins A, B1, B2, B6, and D, while coconut milk has more of vitamins B3, B5, and C. A fair win for soy milk.
When it comes to minerals, the only fortification for the soy milk is calcium, of which it has more than 7x what coconut milk has. The coconut milk, however, has more copper, iron, magnesium, phosphorus, and potassium. An easy win for coconut milk.
Adding up the sections gives us a win for soy milk—but if consumed in moderation as part of a diet otherwise low in saturated fat, a case could be made for the coconut.
The real take-away here today is not this specific head-to-head but rather: milks (animal or plant) vary a lot, have a lot of different fortifications and/or additives, and yes that goes even for brands (cow milk brands do this a lot) who don’t advertise their additives because their branding is going for a “natural” look. So, read labels, and make informed decisions about which additives you do or don’t want.
Enjoy!
Want to learn more?
You might like to read:
Take care!
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Related Posts
The Better Brain – by Dr. Bonnie Kaplan and Dr. Julia Rucklidge
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We’ve reviewed books about eating for brain health before, but this is the first time we’ve reviewed one written by clinical psychologists.
What does that change? Well, it means it less focus on, say, reducing beta amyloid plaques, and more on mental health—which often has a more immediate impact in our life.
In the category of criticisms, the authors do seem to have a bit of a double-standard. For example, they criticise psychiatrists prescribing drugs that have only undergone 12-week clinical trials, but they cite a single case-study of a 10-year-old boy as evidence for a multivitamin treating his psychosis when antipsychotics didn’t work.
However, the authors’ actual dietary advice is nonetheless very respectable. Whole foods, nutrients taken in synergistic stacks, cut the sugar, etc.
Bottom line: if you’d like to learn about the impact good nutrition can have on the brain’s health, ranging from diet itself to dietary supplements, this book presents many avenues to explore.
Click here to check out “The Better Brain”, and eat for the good health of yours!
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How Useful Is Hydrotherapy?
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Hyyyyyyydromatic…
Hydrotherapy is a very broad term, and refers to any (external) use of water as part of a physical therapy. Today we’re going to look at some of the top ways this can be beneficial—maybe you’ll know them all already, but maybe there’s something you hadn’t thought about or done decently; let’s find out!
Notwithstanding the vague nature of the umbrella term, some brave researchers have done a lot of work to bring us lots of information about what works and what doesn’t, so we’ll be using this to guide us today. For example:
Scientific Evidence-Based Effects of Hydrotherapy on Various Systems of the Body
Swimming (and similar)
An obvious one, this can for most people be a very good full-body exercise, that’s exactly as strenuous (or not) as you want/need it to be.
It can be cardio, it can be resistance, it can be endurance, it can be high-intensity interval training, it can be mobility work, it can be just support for an aching body that gets to enjoy being in the closest to zero-gravity we can get without being in freefall or in space.
See also: How To Do HIIT (Without Wrecking Your Body)
Depending on what’s available for you locally (pool with a shallow area, for example), it can also be a place to do some exercises normally performed on land, but with your weight being partially supported (and as a counterpoint, a little resistance added to movement), and no meaningful risk of falling.
Tip: check out your local facilities, to see if they offer water aerobics classes; because the water necessitates slow movement, this can look a lot like tai chi to watch, but it’s great for mobility and balance.
Water circuit therapy
This isn’t circuit training! Rather, it’s a mixture of thermo- and cryotherapy, that is to say, alternating warm and cold water immersion. This can also be interspersed with the use of a sauna, of course.
See also:
- Ice Baths: To Dip Or Not To Dip?
- Saunas: Health Benefits (& Caveats)
- The Stress Prescription (Against Aging!)
this last one is about thermal shock-mediated hormesis, which sounds drastic, but it’s what we’re doing here with the hot and cold, and it’s good for most people!
Pain relief
Most of the research for this has to do with childbirth pain rather than, for example, back pain, but the science is promising:
Post-exercise recovery
It can be tempting to sink into a hot bath, or at least enjoy a good hot shower, after strenuous exercise. But does it help recovery too? The answer is probably yes:
Effect of hot water immersion on acute physiological responses following resistance exercise
For more on that (and other means of improving post-exercise recovery), check out our previous main feature:
How To Speed Up Recovery After A Workout (According To Actual Science)
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4 Tips To Stand Without Using Hands
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The “sit-stand” test, getting up off the floor without using one’s hands, is well-recognized as a good indicator of healthy aging, and predictor of longevity. But what if you can’t do it? Rather than struggling, there are exercises to strengthen the body to be able to do this vital movement.
Step by step
Teresa Shupe has been teaching Pilates professionally full-time for over 25 years, and here’s what she has to offer in the category of safe and effective ways of improving balance and posture while doing the sitting-to-standing movement:
- Squat! Doing squats (especially deep ones) regularly strengthens all the parts necessary to effectively complete this movement. If your knees aren’t up to it at first, do the squats with your back against a wall to start with.
- Roll! On your back, cross your feet as though preparing to stand, and rock-and-roll your body forwards. To start with you can “cheat” and use your fingertips to give a slight extra lift. This exercise builds mobility in the various necessary parts of the body, and also strengthens the core—as well as getting you accustomed to using your bodyweight to move your body forwards.
- Lift! This one’s focusing on that last part, and taking it further. Because it may be difficult to get enough momentum initially, you can practice by holding small weights in your hands, to shift your centre of gravity forwards a bit. Unlike many weights exercises, in this case you’re going to transition to holding less weight rather than more, though.
- Complete! Continue from the above, without weights now; use the blades of your feet to stand. If you need to, use your fingertips to give you a touch more lift and stability, and reduce the fingers that you use until you are using none.
For more on each of these as well as a visual demonstration, enjoy this short video:
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Further reading
For more exercises with a similar approach, check out:
Mobility As A Sporting Pursuit
Take care!
Don’t Forget…
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