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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Water Bath + More Cookbook for Beginners – by Sarah Roslin
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Whether you want to be prepared for the next major crisis that shuts down food supply chains, or just learn a new skill, this book provides the tools!
Especially beneficial if you also grow your own vegetables, but even you just buy those… Home-canned food is healthy, contains fewer additives and preservatives, and costs less in the long run.
Roslin teaches an array of methods, including most importantly:
- fermentation and pickling
- water bath canning, and
- pressure canning.
As for what’s inside? She covers not just vegetables, but also fruit, seafood, meat… Basically, anything that can be canned.
The book explains the tools and equipment you will need as well as how to perform it safely—as well as common mistakes to avoid!
Lest we be intimidated by the task of acquiring appropriate equipment, she also walks us through what we’ll need in that regard too!
Last but not least, there’s also a (sizeable) collection of simple, step-by-step recipes, catering to a wide variety of tastes.
Bottom line: a highly valuable resource that we recommend heartily.
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Coconut vs Avocado – Which is Healthier?
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Our Verdict
When comparing coconut to avocado, we picked the avocado.
Why?
In terms of macros, avocado is lower in carbs and also in net carbs—coconut’s a little higher in fiber, but not enough to make up for the difference in carbs nor, when it comes to glycemic index and insulin index, the impact of coconut’s much higher fat content on insulin responses too. On which note, while coconut’s fats are broadly considered healthy (its impressive saturated fat content is formed of medium-chain triglycerides which, in moderation, are heart-healthy), avocado’s fats are even healthier, being mostly monounsaturated fat with some polyunsaturated (and about 15x less saturated fat). All in all, a fair win for avocado on the macros front, but coconut isn’t bad in moderation.
When it comes to vitamins, avocados are higher in vitamins A, B1, B2, B3, B5, B6, B9, C, E, K, and choline. Most of those differences are by very large margins. Coconuts are not higher in any vitamins. A huge, easy, “perfect score” win for avocados.
In the category of minerals, however, it’s coconut’s turn to sweep with more calcium, copper, iron, magnesium, manganese, phosphorus, zinc, and selenium—though the margins are mostly not nearly as impressive as avocado’s vitamin margins. Speaking of avocados, they do have more potassium than coconuts do, but the margin isn’t very large. A compelling win for coconut’s mineral content.
Adding up the sections, we get to a very credible win for avocados, but coconuts are also very respectable. So, as ever, enjoy both (although we do recommend exercising moderation in the case of coconuts, mainly because of the saturated fat content), and if you’re choosing between them for some purpose, then avocado will generally be the best option.
Want to learn more?
You might like to read:
- Can Saturated Fats Be Healthy? ← defying Betteridge’s Law here!
- Avocado, Coconut & Lime Crumble Pots ← if you do want to enjoy both, here’s a fabulous way to do so in style
Take care!
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Pistachios vs Pecans – Which is Healthier?
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Our Verdict
When comparing pistachios to pecans, we picked the pistachios.
Why?
Firstly, the macronutrients: pistachios have twice as much protein and fiber. Pecans have more fat, though in both of these nuts the fats are healthy.
The category of vitamins is an easy win for pistachios, with a lot more of vitamins A, B1, B2, B3, B6, B9, C, and E. Especially the 8x vitamin A, 7x vitamin B6, 4x vitamin C, and 2x vitamin E, and as the percentages are good too, these aren’t small differences. Pecans, meanwhile, boast only a little more vitamin B5 (pantothenic acid, the one whose name means “it’s everywhere”, because that’s how easy it is to get it).
In terms of minerals, pistachios have more calcium, iron, phosphorus, potassium, and selenium, while pecans have more manganese and zinc. So, a fair win for pistachios on this one.
Adding up the three different kinds of win for pistachios means that *drumroll* pistachios win overall, and it’s not close.
As ever, do enjoy both though, because diversity is healthy!
Want to learn more?
You might like to read:
Take care!
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Hard to Kill – by Dr. Jaime Seeman
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We’ve written before about Dr. Seeman’s method for robust health at all ages, focussing on:
- Nutrition
- Movement
- Sleep
- Mindset
- Environment
In this book, she expands on these things far more than we have room to in our little newsletter, including (importantly!) how each interplays with the others. She also follows up with an invitation to take the “Hard to Kill 30-Day Challenge”.
That said, in the category of criticism, it’s only 152 pages, and she takes some of that to advertise her online services in an effort to upsell the reader.
Nevertheless, there’s a lot of worth in the book itself, and the writing style is certainly easy-reading and compelling.
Bottom line: this book is half instructional, half motivational, and covers some very important areas of health.
Click here to check out “Hard to Kill”, and enjoy robust health at every age!
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Which Sugars Are Healthier, And Which Are Just The Same?
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From Apples to Bees, and High-Fructose Cs
We asked you for your (health-related) policy on sugar. The trends were as follows:
- About half of all respondents voted for “I try to limit sugar intake, but struggle because it’s in everything”
- About a quarter of all respondents voted for “Refined sugar is terrible; natural sugars (e.g. honey, agave) are fine”
- About a quarter of all respondents voted for “Sugar is sugar and sugar is bad; I avoid it entirely”
- One (1) respondent voted for “Sugar is an important source of energy, so I consume plenty”
Writer’s note: I always forget to vote in these, but I’d have voted for “I try to limit sugar intake, but struggle because it’s in everything”.
Sometimes I would like to make my own [whatever] to not have the sugar, but it takes so much more time, and often money too.
So while I make most things from scratch (and typically spend about an hour cooking each day), sometimes store-bought is the regretfully practical timesaver/moneysaver (especially when it comes to condiments).
So, where does the science stand?
There has, of course, been a lot of research into the health impact of sugar.
Unfortunately, a lot of it has been funded by sugar companies, which has not helped. Conversely, there are also studies funded by other institutions with other agendas to push, and some of them will seek to make sugar out to be worse than it is.
So for today’s mythbusting overview, we’ve done our best to quality-control studies for not having financial conflicts of interest. And of course, the usual considerations of favoring high quality studies where possible Large sample sizes, good method, human subjects, that sort of thing.
Sugar is sugar and sugar is bad: True or False?
False and True, respectively.
- Sucrose is sucrose, and is generally bad.
- Fructose is fructose, and is worse.
Both ultimately get converted into glycogen (if not used immediately for energy), but for fructose, this happens mostly* in the liver, which a) taxes it b) goes very unregulated by the pancreas, causing potentially dangerous blood sugar spikes.
This has several interesting effects:
- Because fructose doesn’t directly affect insulin levels, it doesn’t cause insulin insensitivity (yay)
- Because fructose doesn’t directly affect insulin levels, this leaves hyperglycemia untreated (oh dear)
- Because fructose is metabolized by the liver and converted to glycogen which is stored there, it’s one of the main contributors to non-alcoholic fatty liver disease (at this point, we’re retracting our “yay”)
Read more: Fructose and sugar: a major mediator of non-alcoholic fatty liver disease
*”Mostly” in the liver being about 80% in the liver. The remaining 20%ish is processed by the kidneys, where it contributes to kidney stones instead. So, still not fabulous.
Fructose is very bad, so we shouldn’t eat too much fruit: True or False?
False! Fruit is really not the bad guy here. Fruit is good for you!
Fruit does contain fructose yes, but not actually that much in the grand scheme of things, and moreover, fruit contains (unless you have done something unnatural to it) plenty of fiber, which mitigates the impact of the fructose.
- A medium-sized apple (one of the most sugary fruits there is) might contain around 11g of fructose
- A tablespoon of high-fructose corn syrup can have about 27g of fructose (plus about 3g glucose)
Read more about it: Effects of high-fructose (90%) corn syrup on plasma glucose, insulin, and C-peptide in non-insulin-dependent diabetes mellitus and normal subjects
However! The fiber content (in fruit) mitigates the impact of the fructose almost entirely anyway.
And if you take fruits that are high in sugar and/but high in polyphenols, like berries, they now have a considerable net positive impact on glycemic health:
- Polyphenols and Glycemic Control
- Polyphenols and their effects on diabetes management: A review
- Dietary polyphenols as antidiabetic agents: Advances and opportunities
You may be wondering: what was that about “unless you have done something unnatural to it”?
That’s mostly about juicing. Juicing removes much (or all) of the fiber, and if you do that, you’re basically back to shooting fructose into your veins:
- Effect of Fruit Juice on Glucose Control and Insulin Sensitivity in Adults: A Meta-Analysis of 12 Randomized Controlled Trials
- Intake of Fruit, Vegetables, and Fruit Juices and Risk of Diabetes in Women
Natural sugars like honey, agave, and maple syrup, are healthier than refined sugars: True or False?
True… Sometimes, and sometimes marginally.
This is partly because of the glycemic index and glycemic load. The glycemic index scores tail off thus:
- table sugar = 65
- maple syrup = 54
- honey = 46
- agave syrup = 15
So, that’s a big difference there between agave syrup and maple syrup, for example… But it might not matter if you’re using a very small amount, which means it may have a high glycemic index but a low glycemic load.
Note, incidentally, that table sugar, sucrose, is a disaccharide, and is 50% glucose and 50% fructose.
The other more marginal health benefits come from that fact that natural sugars are usually found in foods high in other nutrients. Maple syrup is very high in manganese, for example, and also a fair source of other minerals.
But… Because of its GI, you really don’t want to be relying on it for your nutrients.
Wait, why is sugar bad again?
We’ve been covering mostly the more “mythbusting” aspects of different forms of sugar, rather than the less controversial harms it does, but let’s give at least a cursory nod to the health risks of sugar overall:
- Obesity and associated metabolic risk
- Main contributor to non-alcoholic fatty liver disease
- Increased risk of heart disease
- Insulin resistance and diabetes risk
- Cellular aging (shortened telomeres)
- 95% increased cancer risk
That last one, by the way, was a huge systematic review of 37 large longitudinal cohort studies. Results varied depending on what, specifically, was being examined (e.g. total sugar, fructose content, sugary beverages, etc), and gave up to 200% increased cancer risk in some studies on sugary beverages, but 95% increased risk is a respectable example figure to cite here, pertaining to added sugars in foods.
And finally…
The 56 Most Common Names for Sugar (Some Are Tricky)
How many did you know?
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The Healthiest Bread Recipe You’ll Probably Find
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It’s Q&A Day at 10almonds!
Have a question or a request? You can always hit “reply” to any of our emails, or use the feedback widget at the bottom!
In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!
As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!
So, no question/request too big or small
❝[About accidental scalding with water] Is cold water actually the best immediate treatment for a burn? Maybe there is something better, or something I should apply after the cold water.❞
If this is a case of spilled tea or similar—as in your story, which (apologies) we clipped for brevity—indeed, cold running water is best, and nothing else should be needed. It’s up to you whether you want to invest the time based on the extent of the scalding, but 10 minutes is recommended to minimize tissue damage.
If it’s a more severe scalding or burning, seek medical attention immediately. If it’s a burn to anywhere other than the airway, cold running water is still best for 10 minutes, but if you have to choose between that and professional medical attention, don’t delay the help.
If it’s a burn you’ve given 10 minutes of cold running water and it still hurts and/or has blistered, cover it in a sterile, non-adhesive dressing that extends well beyond the visible burn (because the actual damage probably extends further, and you don’t want to find this out the hard way later). If the burn is to the face, do still irrigate but not cover it; wait for help.
Do not apply any kind of cream, lotion, oil, etc. No matter how tempting, no matter where the burn is.
All of the above also goes for splashed oil, chemical burns, and electrical burns too (but obviously, make sure to get away from the electricity first).
Source: this ex-military writer was trained for this sort of thing and, suffice it to say, has dealt with more serious things than spilled tea before now.
Legal note: notwithstanding the above, we are a health science newsletter, not paramedics. Also, circumstances may differ, and best practices may change. In the case of serious injury, call emergency services first, and follow their instructions over ours.
Take care!
Don’t Forget…
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