Alzheimer’s Sex Differences May Not Be What They Appear

⏰ IN A RUSH?

Today’s 30-Second Summary

If you don’t have time to read the whole email today, here are some key takeaways:

• Women get Alzheimer’s at nearly twice the rate than men do, and deteriorate more rapidly after onset, too.

  • A large part of this is traceable to hormonal sex differences in immune response and metabolism

  • But it’s the opposite of what you might think, because of the age-bracket that tends to get Alzheimer’s—as it turns out, menopause (and the resultant drop in estrogen in a body that’s accustomed to running on estrogen) may be a big factor.

• If you’re looking for more family-oriented quality time this holiday season, today’s sponsor Search Party may be just the thing!

Read on to learn about these things and more…

👀 WATCH AND LEARN

Qigong | Basic Exercises | Bouncing on the Toes to Eliminate the Hundred Illnesses (2:17)

The video starts at 0:23, so we’ve skipped to that point for you:

Click Here If The Embedded Video Doesn’t Load Automatically!

Prefer text? There is a text explanation of how to do the exercise (and why), under the video.

Here, also, are some quick notes of our own:

"To eliminate the hundred illnesses" is quite a strong claim, so to give at least a little explanation:

This one's about three main things:

1. Good posture

2. Good breathing

3. Good organ health

…all of which have a lot of good effects for the body.

The text description speaks of the exercise "massaging the kidneys"; it may be more helpful to view the exercise as undoing some of the damage caused by sitting, by encouraging your organs back into the places they are supposed to be.

Remember, your insides are not a neat-and-tidy anatomy mannequin; you are a sack of squishy things. Think of this exercise as the anatomical equivalent of fluffing your pillow-stuffing back into shape.

Want to watch it, but not right now? Bookmark it for later 🔖

🧠 MAIN FEATURE

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:

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.

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.

Specifically:

Source: Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women

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:

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!

❤️ OUR SPONSORS MAKE THIS PUBLICATION POSSIBLE

Search Party: Chaos at the Park

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🌍 AROUND THE WEB

What’s happening in the health world…

• Reducing vivid imagery that fuels addiction cravings

• In the lab: an mpox mRNA vaccine that's outperforming its old-school predecessor

• What leads people to take action on disease prevention?

• Research investigates music's effects on cells with implications for diabetes treatment

• Study sheds light on sporadic early-onset Alzheimer's disease, potential target for novel treatment

• Following a Mediterranean diet reduces the risk of cognitive decline in older people

• Do GLP-1 receptor agonists improve cardiovascular health independently of weight loss?

More to come tomorrow!

📖 ONE-MINUTE BOOK REVIEW

Winter Wellness: Nourishing recipes to keep you healthy when it's cold – by Rachel de Thample

Winter is often the season of comfort foods and, in much of the Western world, there's a holiday season slide of forgotten diets and instead sugar, alcohol, pastry, and the like.

What de Thample does here is an antidote to all that, without sacrificing happiness and celebration.

Before the recipes get started, she has a chapter on "food as medicine", and to our immense surprise, proceeds to detail, accurately, many categories such as

• Foods for immune health

• Foods against inflammation

• Foods for gut health

• Foods against aging

• Foods for energy levels

• Foods against anxiety

• Foods for hormonal balance

...and so forth, with lists of ingredients that fit into each category.

Then in the rest of the book, she lays out beautiful recipes for wonderful dishes (and drinks) that use those ingredients, without unhealthy additions.

The recipes are, by the way, what could best be categorized as "fancy". However, they are fancy in the sense that they will be impressive for entertaining, and (again, to our great surprise) they don't actually call for particularly expensive/rare ingredients, nor for arcane methods and special equipment. Instead, everything's astonishingly accessible to put together and easy to execute.

Bottom line: if you'd like to indulge this winter, but would like to do so healthily, this is an excellent way to do so.

Click here to check out Winter Wellness, and level-up your seasonal health and happiness!

Wishing you a Wednesday full of wellness,

The 10almonds Team