Our understanding for how our brain ages and why our memory slips after age 50 have been completely revamped through 2 new landmark studies of the microglia, the brain immune cells A major inflection occurs around age 50
erictopol.substack.com/p/why-our-memo…

For medical information, general AI frontier models (Google, OpenAI, Anthropic) outperformed specialized @EvidenceOpen and @UpToDate as assessed by 12 US clinicians, randomized and blinded to which model and extensive testing/benchmarks. This was not anticipated. @NatureMedicine
nature.com/articles/s4159… >65% of US physicians use OpenEvidence, with 27 million prompts in April
nbcnews.com/tech/tech-news…

A new study links GLP-1 drugs and 30-35% reduced incidence of breast cancer, using matched-pair propensity analysis

Confirms other association studies but still no proofascopubs.org/doi/10.1200/OP… Very good review on this topic, by @DanielJDrucker @NatureCancer
nature.com/articles/s4301…

If you're interested in how AI grew up over the past 15 years, and where it's headed, this new book tells the story in a riveting, page-turner way. In the new Ground Truths with @scmallaby In 2010, when @GoogleDeepMind was formed, well before deep learning was taking hold, @demishassabis predicted AGI by 2030 and called out the use of agents

Physical activity and the reduction of all-cause mortality, from 2 very large prospective cohorts
1. The relationship is non-linear, suggesting a threshold effect for many types of exercise as seen below 2. Engaging in > 1 type of physical activity was generally correlated with better outcomes compared with 1 type (T1,2,3)

People age 70+ should not be taking aspirin at any dose for prevention. Results of randomized trials show higher risk of all-cause mortality, major bleeding events and deaths from cancer. p 153, SUPER AGERS book President Trump takes 325 mg aspirin/day. The randomized trials tested 75-81 mg/day. His doctors recommended low-dose aspirin for heart event prevention. That recommendation is ill-founded based upon best evidence in older individuals.
nejm.org/doi/full/10.10…
academic.oup.com/eurheartj/arti…

As I wrote in SUPER AGERS, the immune system is the key to modulating our aging process and the opportunity to extend healthspan. Today @NatureAging 7 new articles, summarized here, that reinforce its central role
nature.com/articles/s4358… Inflammaging: with aging comes untoward inflammation, a summary graphic
nature.com/articles/s4358…

The new special issue @ScienceMagazine features Immunity with 4 outstanding review papers, 5★
Our immune system over the lifespan, sex differences, influence on physiology, and host antiviral defenses science.org/toc/science/cu… Our immune system as we age: the path to immunosenesence and inflammaging
science.org/doi/10.1126/sc…

We've learned a lot more about the principal drivers of age-related diseases in the past few weeks. And that leads to a unified model to pull it all together. (open-access) I review 4 new reports, summarized here:
1. The proteins from senescent cells predict age-related clinical outcomes
2. A new epigenetic age clock connects the dots between aging, the immune system, inflammation and lifestyle factors
3. People with a fast pace of aging had an increased risk of cognitive impairment, age-related diseases, disability, and mortality
4. The Importance of “Immune Resilience” for Healthspan

Most people haven’t heard of this test, which is available in the US. It accurately predicts Alzheimer’s (not just if there’s a risk, but when). It is favorably affected by exercise and likely many other lifestyle factors.
Here’s (almost) everything we know about it. In Ground Truths (link in my profile d/t X-suppression) Here's the response to exercise

A major @Nature paper this week found a significant decline in dementia after an outdated Shingles vaccine.
I've reviewed the study and many other relevant ones in a new Ground Truths (link in profile) A Table from the post

The vaccine against Shingles helps protect against dementia, results of a natural experiment, adding to prior evidence
"implications are profound"
New @Nature
nature.com/articles/s4158…
nature.com/articles/d4158…

https://x.com/EricTopol/status/1901957986727117069

Of >105,000 participants with 30-year follow-up, only 9.3% achieved healthy aging (age 70, w/o any chronic diseases). Their diet was significantly associated with this outcome🧵 @NatureMedicine These are the specific foods that were linked with healthy aging and other outcomes. Green-favorable; Red-unfavorable

A paper on microplastics accumulating in the brain was just published @NatureMedicine, open-access
I review the background and major implications in a new Ground Truths edition (link in my profile)nature.com/articles/s4159…
The human brain:
—had 7-30 times more accumulation of microparticles (MPs) than the liver or kidney (organs with previously documented high propensity)
—from people with dementia had 5X accumulation of MPs compared with non-dementia
—there was a marked increase of accumulation over recent years

Three new @NEJM reports on #H5N1 today
1. An overview by @MichaelGIsonMD and @DrJeanneM
"urgent need for vigilant surveillance of emerging mutations and assessment of the threat of human-to-human transmission"
2. Report of the 13-year-old Canadian girl who developed acute respiratory failure. Sequence of her H5N1 revealed 3 mutations that may be linked to higher virulence and adaptation to human cell binding

We're learning how to control the immune response, like a rheostat, even in the brain. Implications for understanding the basis and potential treatment of autoimmune conditions like multiple sclerosis, #LongCovid, #MECFS, and brain cancer.
A brief review of 6 recent, important reports
in the new Ground Truths, open-access Such as Programming T cells with brain-specific proteins and payloads
@ScienceMagazine science.org/doi/10.1126/sc…

New @NEJM
A whopping (~90%) reduction of progression to Type 2 diabetes with tirzepatide (GLP-1 drug, dual receptor) vs placebo in a randomized trial of >2,500 participants with obesity, absolute reduction of 10/100 treated

by @AniaJastreboff and collaboratorsnejm.org/doi/full/10.10… In other GLP-1 new publications today
—Country-wide Sweden reduced hospitalizations for alcohol or substance abuse with these drugs
jamanetwork.com/journals/jamap… @JAMAPsych
—Concerns about discontinuation
jamanetwork.com/journals/jama/… @JAMA_current

A dedicated issue of @ScienceTM on #LongCovid
—Sex-specific differences, with perspective by @VirusesImmunity and @SilvaJ_C
—Insights for therapies @AndreaCoxMDPhD
—Deconvoluting "Osler's Web" @MichaelPelusoMD @DeeksSteven @DrMaureenHanson @SaydahSharon
—+RECOVER Trial, Lyme disease

science.org/toc/stm/16/773

An elegant @Nature study by @AkassoglouLab has illuminated our understanding of the role of fibrin (component of blood clots), #SARSCoV2, and brain inflammation in Covid and #LongCovid.
This discovery and more in the new Ground Truths podcast, with transcript, key figures (such as as the one below) and citations. Open-access. Link in my profile.
A clip from our conversation. Unknowingly, @AkassoglouLab was gearing up for understanding this complex pathophysiology for many years before Covid hit

Covid and increased risk of major adverse cardiovascular events (MACE) 3-years out

2-fold increased for any severity of Covid
~4-fold increase for Covid requiring hospitalization
"a coronary artery disease equivalent"
interaction with non-O blood types
@uk_biobankahajournals.org/doi/10.1161/AT… "A major finding from our analyses was that the risk
of MACE among the subset of hospitalized COVID-
19 cases without known CVD (ie, primary prevention
patients) was comparable to (or even slightly higher than) the risk in patients with CVD, PAD, or diabetes but without COVID-19."

New US Covid genomic surveillance
The KP.3.1.1 variant is on the move to become dominant, more of a challenge to our immune response than KP.3 and prior variants (especially without new KP.2 booster when we need it for high-risk individuals) It's the deletion 31/31 that makes the KP.3.1.1 spike different, but otherwise 2 mutations away from KP.2 (R346T and Q493E)