#742

The healthy diets all focus on whole grains, fruits, vegetables, fish, nuts, and poultry. Fried foods, dairy, and meat are discouraged. It’s thought that this helps reduce stress inside the body and thus protect the brain from harm.

Open access paper:

Association of Mediterranean, high-quality, and anti-inflammatory diet with dementia in UK Biobank cohort

Conclusion

Greater adherence to Mediterranean, MIND, and high-quality diets is associated with a lower risk of dementia, while pro-inflammatory diets increase the risk. High-quality anti-inflammatory diets play a
significant role in reducing the risk of dementia, with stronger effects observed in specific subgroups.

https://www.sciencedirect.com/science/article/pii/S1279770725000880?via%3Dihub

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#743
#744
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#745

A good article by Christin Glorioso on APOE4 and what to do about it:

APOE and Alzheimer’s

Understanding the most common Alzheimer’s risk gene and what to do about it

I was sitting in NeuroAge’s headquarters when I decided to “rip the bandaid off” and look at my genetic risk for Alzheimer’s Disease. I had been putting it off because I had for most of my life thought that there wasn’t much I could do about it.

One of my great grandmothers, one of my grandmothers, and one of my aunts all have had Alzheimer’s and it has been devastating. Imagining my own cognitive decline and the distress that it could put on others around me is a scary thought.

It nearly took my breath away to find out that I had one APOEε4 allele, the most common genetic factor for Alzheimer’s.

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#746
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#747

Nice… I have an egg every morning when possible - need that protein kick to start the day.

And, all those other great nutrients… and brain health too.

The Mayo clinic agrees.

Eggs: Are they good or bad for my cholesterol? - Mayo Clinic.

Chicken eggs are an affordable source of protein and other nutrients.

Most healthy people can eat up to seven eggs a week without increasing their risk of heart disease.

Not that long ago eggs were touted as a definite :-1: no, due to cholesterol. Was considered equal to smoking.

Diet gurus seem to get it wrong more often then not. Same with natural sun. A little is needed.

Thanks for the update.

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#748

You can also supplement with small amounts of citicoline. Eggs are like any other food. You might already be getting some nutrients from other sources - vit. B12, vit. D, vit. B2, vit. A, choline, lutein, and so on. It also has protein… with a lot of methionine. In some diets eggs will be a big plus, in other diets less so. Is there something unique in eggs that you need even at the cost of the amino-acid profile? Then go ahead. If you don’t consume much protein from other sources, eggs are a good source. Again, there are no magical superfoods, you have to see everything in the context of the whole diet.

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#749

Avoid air pollution…

Source research:

Long-term air pollution exposure and incident dementia: a systematic review and meta-analysis

Findings

The search generated 15 619 records, of which 51 studies met the inclusion criteria for data extraction. After excluding studies due to population overlap and missing continuous effect estimates, 32 studies reported on exposure–outcome pairs that met the threshold of three or more studies, and were included in meta-analyses of adjusted effect estimates for incident dementia and/or in subgroup analyses of dementia subtypes. In meta-analyses of incident dementia, we identified a dementia diagnosis to be significantly associated with long-term exposure to PM2·5 (21 studies, n=24 030 527, pooled adjusted hazard ratio (HR) per 5 μg/m3 increase in exposure, 1·08 [95% CI 1·02–1·14]; I 2=95%), nitrogen dioxide (16 studies, n=17 228 429, pooled adjusted HR per 10 μg/m3 increase, 1·03 [1·01–1·05]; I 2=84%), and black carbon/PM2·5 absorbance (six studies, n=19 421 865, pooled adjusted HR per 1 μg/m3 increase, 1·13 [1·01–1·27]; I 2=97%). We found no significant association for exposure to nitrogen oxides (five studies, n=241 409, pooled adjusted HR per 10 μg/m3 increase, 1·05 [0·97–1·13]; I 2=44%), PM10 (four studies, n=246 440, pooled adjusted HR per 15 μg/m3 increase, 1·52 [0·80–2·87]; I 2=82%), or annual ozone (four studies, n=419 972, pooled adjusted HR per 45 μg/m3 increase, 0·82 [0·35–1·92]; I 2=69%), with moderate to considerable heterogeneity between studies in these pooled analyses. Of the 32 studies overall, three (9%) had a probably high risk of bias in one of seven domains; all other studies had ratings of probably to definitely low risk of bias. The overall certainty of evidence of studies in the systematic review was moderate.

https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(25)00118-4/fulltext

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#750

"Initially developed as a way to help the immune system better recognize and attack tumors, ONC-841 has also shown promise in addressing the mechanisms underlying Alzheimer’s disease in preclinical models. OncoC4 is presenting research presented at AAIC, which it says demonstrates that inhibiting SIGLEC 10 activity in the brain could restore microglia, the brain’s resident immune cells, to a more functional state. These cells play a critical role in clearing protein aggregates such as amyloid plaques and tau tangles – known hallmarks of Alzheimer’s disease.

In two mouse models of Alzheimer’s disease, ONC-841 treatment improved microglial migration and ability to clear amyloid plaques, reduced levels of phosphorylated tau in plasma and alleviated structural and functional abnormalities linked to disease progression. According to OncoC4, the treated mice also exhibited measurable improvements in memory and learning, suggesting that immune modulation targeting SIGLEC 10 could influence both pathological and cognitive outcomes."

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#751

I had a look at the Stanford study and am interested in your further thoughts because I had i slightly different interpretation.

Admittedly this is a cohort study only (so confounders…) but highest quartile for EPA had a big impact on All Cause Mortality regardless of DHA. 0.48 Hazard Ratio even with high DHA!

I appreciate that the study shows that we can do even better (0.36 HR if EPA high and DHA low) but I’m thinking that the overwhelming message is to increase your EPA intake. Not avoid DHA at all costs ( because there wasnt a clear signal when looking at DHA alone: “However, after the adjustment for baseline differences, the risk of MACE was not significant for DHA”)

My reading is that there was a statistical signal when looking at DHAs impact in potentially modifying EPAs benefit. But not really
strong enough to find significance from DHA levels alone.

Given the limitations of the study (use of quartiles in this study, and the relatively small cohort size) this Isn’t completely surprising. But I think if someone offered me a ‘balanced’ omega 3 tablet, and i only had this study to go on - I’d take it.

“While the unadjusted hazard ratio (HR) of MACE for the highest (fourth) quartile of EPA was 0.48 (95% CI: 0.35, 0.67) compared to the lowest quartile, the adjustment for DHA improved the HR to 0.36 (95% CI: 0.22, 0.58), suggesting an adverse effect modification by DHA”

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#752

I agree with that and the way I sum it up is: “Supplement with EPA but don’t cut on fish intake”.

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#753

Yes, whenever I get lost in the rabbit hole of EPA DHA research I end up opting for sardines on toast.

My concern with the EPA only supplements is that the processing needed to refine may be potentially negative. Heat and enzymes can be part of the processing.

The research suggests a high EPA / low DHA status is better than high EPA /high DHA.
And it suggests a high EPA /High DHA is much better than Low EPA status.
But is there any evidence that high EPA / highly processed Omega 3 supplements are better than less processed balanced EPA/DHA supplement?
(part of the problem is that I’ve never been convinced by any omega 3 supplementation studies).
Back to my sardines on toast…

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#754

Cell-type-directed network-correcting combination therapy for Alzheimer’s disease

https://www.cell.com/cell/fulltext/S0092-8674(25)00737-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007378%3Fshowall%3Dtrue

Reversing Alzheimer’s damage: Two cancer drugs demonstrate surprising power

#755

Since MR which is basically genetic studies are one of the best tools in medicine for predicting disease and finding drugs (drugs which have genetic support have higher likelihood of succeeding), could slow progress in Alzheimer’s Disease and dementia be because of genetic research underpinning cognitive decline with age being controversial?

Recently, claims of improved prediction of cognitive ability: predictor correlation of ~ 0.4 or 0.5 with actual IQ scores. I wrote ~15 years ago that we would surpass this level of prediction, given enough data. I have maintained for a long time that complex trait prediction is largely data-limited. Progress has been slow as there is almost zero funding to accumulate cognitive scores in large biobanks. This is because of persistent ideological attacks against this area of research.

Almost all researchers in genomics recognize human cognitive ability as an important phenotype. For example, cognitive decline with age should be studied carefully at a genetic level, which requires creation of these datasets. However most researchers are AFRAID to voice this in public because they will be attacked by leftists.

I note that as the Overton window opens some cowardly researchers who were critical of GP [genomic prediction] in its early days (even for disease risk reduction!) are now supporting companies that openly advertise embryo IQ selection.

https://x.com/hsu_steve/status/1951263974747488601#m

I don’t personally care that much about IQ/intelligence, health seem like most important especially in the age of AI, I don’t think anyone believes their kids or grandkids will be smarter than AI. But controversy surrounding genetic research for cognitive abilities might slow down some forms of research that can help with cognitive aging.

Genetics is the most important area of medicine for sure, except randomized trials of course.

#756

Neurofilament light chain (NfL) is a new blood test that can be used to screen for neurodegenerative conditions. It has good sensitivity but lacks specificity. Linked below is a short article from Mayo. The neuroscientist notes that:

“If NfL is elevated, the patient’s cognitive decline is likely due to neurodegeneration. If NfL is normal, then the most likely cause of cognitive decline is a non-neurodegenerative process,” Dr. Algeciras says.

”“A blood test for NfL is a feasible screening tool that can reduce the number of tests that physicians order up front, which will obviously have an economic benefit.”

In other words, it can be used for screening, and then if the result is elevated, additional tests can be done to determine the cause. It may allow people to catch a neurodegenerative process early.

Marek Diagnostics offers it through Labcorp for $406.

https://news.mayocliniclabs.com/2022/05/17/nflc-test-in-focus/

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#757

A new study, which included 2,100 older Americans at risk of dementia, found significant improvement in cognition by incorporating regular moderate to high-intensity physical exercise, adherence to what’s known as the mind diet, such as grains, leafy greens, and berries, mandatory social engagement, as well as cardiovascular health monitoring.

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#758

Alzheimer’s disease may start in your gut, new research finds

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#759

Lithium Battery of Tests

Did researchers just find a glimmer of hope in the quest to fight Alzheimer’s? “Seven years of investigation by scientists at Harvard Medical School have revealed that the loss of the metal lithium plays a powerful role in Alzheimer’s disease, a finding that could lead to earlier detection, new treatments and a broader understanding of how the brain ages. Researchers led by Bruce A. Yankner, professor of genetics and neurology at Harvard Medical School, reported that they were able to reverse the disease in mice and restore brain function with small amounts of the compound lithium orotate, enough to mimic the metal’s natural level in the brain.” Research on reversing Alzheimer’s reveals lithium as potential key.

https://www.msn.com/en-us/science/biochemistry/research-on-reversing-alzheimer-s-reveals-lithium-as-potential-key/ar-AA1K1DXW

Open access paper:

Lithium deficiency and the onset of Alzheimer’s disease

The earliest molecular changes in Alzheimer’s disease (AD) are poorly understood1,2,3,4,5. Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration. We explored the role of endogenous Li in the brain by depleting it from the diet of wild-type and AD mouse models. Reducing endogenous cortical Li by approximately 50% markedly increased the deposition of amyloid-β and the accumulation of phospho-tau, and led to pro-inflammatory microglial activation, the loss of synapses, axons and myelin, and accelerated cognitive decline. These effects were mediated, at least in part, through activation of the kinase GSK3β. Single-nucleus RNA-seq showed that Li deficiency gives rise to transcriptome changes in multiple brain cell types that overlap with transcriptome changes in AD. Replacement therapy with lithium orotate, which is a Li salt with reduced amyloid binding, prevents pathological changes and memory loss in AD mouse models and ageing wild-type mice. These findings reveal physiological effects of endogenous Li in the brain and indicate that disruption of Li homeostasis may be an early event in the pathogenesis of AD. Li replacement with amyloid-evading salts is a potential approach to the prevention and treatment of AD.

https://www.nature.com/articles/s41586-025-09335-x

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#760

Also discussed there:

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#761
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