Predicting Alzheimers & Dementia (and minimizing risk)

[RapAdmin]

Dementia Prevention Must Begin in Childhood, Not Just Midlife - Neuroscience...

[Beth]

I was taking magtein for a couple of years after learning about it from Attia, but I ceased taking it over a year ago due to not seeing many here taking it and assuming you all knew something I don’t…

Now you all are coming out of the woodworks… *adds to cart.

[RapAdmin]

Scientists reveal the everyday habits that may shield you from dementia

[Beth]

For those of you with a costco membership

I tired and failed to make the image smaller

[desertshores]

Thanks, I never thought to look at Costco for this. Way cheaper than I just paid for mine.

[tananth]

So 3 tablets needed for the 2000mg recommended daily dose, around $0.76 per day from Costco. Same brand available from iherb for $0.99 per day, which can be cheaper than costco with a 25% or higher sales discount.

[Beth]

Here’s a question, if you happen to know…

So, I won’t be taking 3 a day just because I am already taking other mag and a long list of other items…

Does anyone think there is a pro or con to taking 1 per day (smaller dose) vs 3 per day less often?

I imagine it doesn’t matter, but I don’t know how life works

[Tim]

Many of the videos on YouTube are suffering from bloat, like a good magazine article that has been expanded to the size of a dull book. On the other hand, YouTube has a number of great instructional videos, which can help to illuminate a dense and difficult subject. I’ve learned a lot from YouTube, but I tend to stay away talking heads.

[RapAdmin]

Air pollution linked to more severe Alzheimer’s disease, Penn study finds

Exposure to air pollution was associated with worse cases of Alzheimer’s disease in a study that analyzed autopsied brain tissue from several hundred patients.

A study by University of Pennsylvania researchers linked increased exposure to air pollution to worse cases of Alzheimer’s disease. They specifically looked at the smallest category of pollutants: particles with a diameter of 2.5 micrometers or less. That’s at least 30 times smallerthan the average strand of human hair.

Pollutants of this size are considered particularly hazardous and come from a variety of sources, including combustion, car exhaust, and wildfire smoke.

“These particles are small enough that if you inhale them, they pass readily into your bloodstream. Some of it could probably get directly into your brain,” said Edward Lee, the senior author of the study published Sept. 8 in the medical journal JAMA Neurology.

Air pollution linked to more severe Alzheimer’s disease, Penn study finds

[RapAdmin]

Moneta Health Raises Funding to Expand Access to Brain Care

Alzheimer’s Moonshot Community member Moneta Health raised $4.5M to expand access to cognitive care. Focused on brain health, Moneta is pioneering “physical therapy for your brain” through simple, effective, AI-powered exercises over the phone (including landlines). Other rounds this week included new capital for hybrid pediatrics, virtual neurology, enterprise telehealth, and a wave of AI-driven platforms spanning biotech, clinical trials, and women’s health.
» Read on Health Transformer Journal

Apply to Join the Alzheimer’s Moonshot Community — StartUp Health

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Wisdom from the StartUp Health Community

Morning Blend: Cognitive Health Solutions with Moneta Health
Channel 13 Las Vegas News KTNV

Transforming Dementia Care, Zinnia TV with Allyson Schrier
Inspired Caring

Why We Opened the StartUp Health Network to the Ecosystem
StartUp Health NOW

Reimagining Capitalism with Purpose: A Fireside Chat with Vishal Vasishth of Obvious Ventures on the Future of Health
Health Transformer Journal

Health Transformer Spotlight: Meet the Serial Entrepreneur Behind Owl Therapeutics, Helping the Brain Repair Itself
Health Transformer Journal

[RapAdmin]

The great revolution against Alzheimer’s: ‘It’s the first time in human...

[adssx]

Cross linking the other thread for those interested: Air pollution and the effects on health - #64 by RapAdmin

[RapAdmin]

4 vaccines linked to a lower risk of dementia (WaPo)

Studies have found that many vaccines may be associated with a reduced risk of dementia — here are four of the most common ones with the strongest links.

The flu shot

An estimated 47 million to 82 million people in the United States — about 13 to 24 percent of all people — caught influenza, or the flu, during the 2024-2025 season with 27,000 to 130,000 Americans dying as a result, according to preliminary data from the Centers for Disease Control and Prevention. (Flu season generally runs from October to May in North America.)

The shingles vaccine

The shingles vaccine has the strongest evidence for reducing the risk of dementia with multiple large-scale studies in the past two years corroborating the results of older studies.

In one 2025 study, researchers tracked more than 280,000 adults in Wales and found that the shingles vaccine was linked with reducing dementia risk by 20 percent over a seven-year period.

The RSV vaccine

Respiratory syncytial virus, or RSV, is a common respiratory virus that can cause mild, cold-like symptoms in most people, but may cause severe infections in children as well as adults ages 65 and older. (The virus is the leading cause of hospitalization among American infants and causes an estimated 10o to 300 deaths in children under 5, and 6,000 to 10,000 deaths in people 65 or older, every year in the U.S.)

The Tdap vaccine

Several studies have reported that the vaccine against tetanus, diphtheria and pertussis (or whooping cough), or Tdap, is associated with a reduced risk of dementia.

One 2021 study with over 200,000 patients reported that older adults who received both the shingles and Tdap vaccines had further reduced risk of dementia compared with those who only received one of the vaccines.

Read the full story: 4 vaccines linked to a lower risk of dementia (WaPo)

[RapAdmin]

Healthy Habits Can Make Your Brain Up to 8 Years Younger - Neuroscience News

[Tim]

Those are staggering numbers, increasing mild impairment by 38%. But still, you get worse odds in Las Vegas. Choosing between A. B, and C, when all three have their drawbacks, I’ll take sleep. “Sleep that knits up the raveled sleeve of care.”

[RapAdmin]

From Nature:

Swapping old immune cells in the brain with fresh ones could treat disease

Replacing immune cells called microglia holds promise for addressing brain conditions such as Alzheimer’s disease.

A fresh supply of the immune cells that keep the brain tidy might one day help to treat a host of conditions, from ultra-rare genetic disorders to more familiar scourges, such as Alzheimer’s disease.

In the past few months, a spate of new studies have highlighted the potential of a technique called microglia replacement and explored ways to make it safer and more effective. “This approach is very promising,” says Pasqualina Colella, who studies gene and cell therapy at Stanford University School of Medicine in California. “But the caveat is the toxicity of the procedure.”

Read the full article: Swapping old immune cells in the brain with fresh ones could treat disease (Nature)

Background on "Microglial replacement:

Microglia replacement is an emerging experimental technique in neuroscience and geroscience that aims to rejuvenate or reset the brain’s immune system by removing dysfunctional microglia and allowing new, healthy microglia to repopulate the central nervous system (CNS).

Here’s a detailed breakdown:

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1. Background: What Are Microglia?

• Microglia are the resident immune cells of the brain and spinal cord.

• They are critical for:

  • Clearing cellular debris, protein aggregates, and pathogens.
  • Synaptic pruning (removing unnecessary neuronal connections).
  • Maintaining overall CNS homeostasis.

• With age or in disease states (e.g., Alzheimer’s, Parkinson’s, multiple sclerosis), microglia can become chronically activated, dysfunctional, or senescent, producing inflammatory signals that contribute to neurodegeneration.

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2. The Concept of Microglia Replacement

The central idea is to remove the dysfunctional microglia population and allow the brain to repopulate with new, healthy microglia.
This is typically done by:

1. Eliminating resident microglia → usually achieved with drugs that inhibit CSF1R (colony-stimulating factor 1 receptor), which microglia require for survival.
2. Repopulation phase → once the drug is withdrawn, new microglia emerge from CNS-resident progenitors or bone marrow–derived precursors, depending on the protocol.

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3. Key Experimental Techniques

• Pharmacological depletion:

  • CSF1R inhibitors (e.g., PLX3397, PLX5622) can eliminate >90% of microglia in mice within a week.

• Genetic depletion models:

  • Engineered mice where microglia can be selectively ablated when given certain drugs (e.g., diphtheria toxin).

• Bone marrow transplantation approaches:

  • In some studies, after depletion, bone marrow–derived monocytes migrate into the brain and differentiate into microglia-like cells.

• Timing & duration:

  • The depletion is temporary; once the inhibitor is withdrawn, microglia rapidly repopulate within ~1–2 weeks.

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4. Therapeutic Rationale

• Aging brain: “resetting” the microglial population may restore youthful immune surveillance and reduce chronic neuroinflammation.

• Neurodegenerative diseases:

  • Alzheimer’s: Microglia replacement has been shown in mice to reduce β-amyloid plaque burden and improve cognition.
  • Parkinson’s: May reduce α-synuclein pathology.

• Traumatic brain injury and stroke: Replacing dysfunctional microglia may improve recovery and synaptic remodeling.

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5. Evidence from Studies

• Rodent studies:

  • Removal of aged/dysfunctional microglia followed by repopulation leads to improved cognitive performance, restored synaptic density, and reduced neuroinflammatory markers.

• Disease models:

  • In Alzheimer’s mouse models, microglia replacement reduced plaque load and rescued memory performance.

• Longevity & geroscience relevance:

  • Suggests that brain “rejuvenation” may be achievable by periodically refreshing microglial populations, akin to immune system reboot strategies in other tissues.

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6. Challenges and Unknowns

• Origin of repopulating cells:

  • Mostly from CNS-resident progenitors, but in certain contexts bone marrow–derived cells contribute.

• Human translation:

  • Most work is preclinical; safety and feasibility in humans remain uncertain.

• Potential risks:

  • Over-activation or insufficient control of new microglia could cause unwanted inflammation.
  • Temporary vulnerability while microglia are absent.

• Integration with other therapies:

  • May be synergistic with anti-amyloid or anti-tau drugs, or systemic immune rejuvenation.

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7. Clinical Outlook

• Microglia replacement is still at the experimental / preclinical stage.
• Several biotech and academic labs are exploring CSF1R inhibitors or microglia transplantation approaches as potential therapies.
• If successful, this could become a novel class of treatment for neurodegenerative and age-related CNS diseases.

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In summary:
Microglia replacement is like “wiping the slate clean” for the brain’s immune system—removing old, dysfunctional microglia and letting the brain repopulate with new, functional ones. It holds promise for neurodegenerative diseases, brain aging, and CNS injuries, but is still an early-stage technique requiring careful study of safety and long-term effects.

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[RapAdmin]

Sleep Disorders Predict Parkinson’s or Dementia Years Ahead - Neuroscience News

[RapAdmin]

Trying to Unravel Why Alzheimer Disease Is More Common in Women

Approximately 2 out of every 3 people living with Alzheimer disease in the US is a woman, Harvard neuropsychologist Rachel Buckley, PhD, noted. “Women actually tend to live with dementia for much longer than men.”

A recently published study in JAMA Neurology seems to bear that out. The nationwide cohort study used Medicare enrollment data for approximately 5.7 million patients aged 65 years or older who’d been diagnosed with dementia from any cause between 2014 and 2021, with up to 8 years of follow-up. About 3.3 million were women, whereas 2.4 million were men. A year after they were diagnosed with dementia, about 27% of men had died, compared with 22% of women. After accounting for age, comorbidities, access to health care, and other factors, the all-cause mortality rate 1 year after diagnosis was 24% higher for men than for women.

全文：

https://jamanetwork.com/journals/jama/fullarticle/2839498

[DeStrider]

The Sad Case of The Youngest-Ever Alzheimer’s Diagnosis : ScienceAlert The Sad Case of The Youngest-Ever Alzheimer's Diagnosis : ScienceAlert

[RapAdmin]

Do These Two Cancer Drugs Have What It Takes to Beat Alzheimer’s?

A new study finds FDA approved drugs that reverse the gene expression signatures associated with Alzheimer’s.

Scientists at UC San Francisco and Gladstone Institutes have identified cancer drugs that promise to reverse the changes that occur in the brain during Alzheimer’s, potentially slowing or even reversing its symptoms.

The study first analyzed how Alzheimer’s disease altered gene expression, the activity of genes in a cell, in single cells in the human brain. Then, researchers looked for existing drugs that were already approved by the Food and Drug Administration (FDA) and cause the opposite changes to gene expression.

They were looking specifically for drugs that would reverse the gene expression changes in neurons and in other types of brain cells called glia, all of which are damaged or altered in Alzheimer’s disease. Next, the researchers analyzed millions of electronic medical records to show that patients who took some of these drugs as part of their treatment for other conditions were less likely to get Alzheimer’s disease.

When they tested a combination of the two top drugs — both of which are cancer medications — in a mouse model of Alzheimer’s, it reduced brain degeneration in the mice, and even restored their ability to remember.

全文：

Do These Two Cancer Drugs Have What It Takes to Beat Alzheimer’s?

Decoding Alzheimer’s disease at the cellular level reveals promising combination therapy

https://www.cell.com/cell/abstract/S0092-8674(25)01030-X

AI Summary:

The two drugs are letrozole (an aromatase inhibitor) and irinotecan (a topoisomerase-I inhibitor). (考研)

What supports this combo for Alzheimer’s (so far)

How they were picked (human-data–first):

• Researchers built cell-type–specific AD gene-expression “signatures” from single-cell/single-nucleus RNA-seq of human AD brains, then screened drug-perturbation databases (Connectivity Map) to find FDA-approved drugs that reverse these signatures—ideally across multiple brain cell types. Letrozole best countered neuron signatures; irinotecan best countered glial signatures. (家)

Real-world signal:

• Mining ~1.4 million UC Health electronic records (age ≥65), several of the short-listed drugs were associated with a lower subsequent risk of an AD diagnosis (an observational association used as supportive evidence for prioritization). (家)

In-vivo validation (mice with both Aβ and tau pathology):

• Only the combination (letrozole + irinotecan), not either drug alone, significantly:
  • Improved memory/learning performance,
  • Reduced neurodegeneration and protein aggregates (incl. tau clumps), and
  • Reversed disease gene-network states in a cell-type-specific way on single-nucleus transcriptomics of treated brains. (家)

Primary source & status:

• Peer-reviewed paper in Cell: “Cell-type-directed network-correcting combination therapy for Alzheimer’s disease”(Li et al., 2025). The abstract explicitly names letrozole and irinotecan and summarizes the mouse and transcriptomic results. A 2024 bioRxiv preprint (now updated by the Cell paper) contains congruent details. (考研)

Institutional summaries (helpful plain-language overviews with images):

• UCSF and Gladstone press write-ups reiterate the selection logic, the EMR association, and that the combo outperformed monotherapy in the AD mouse model (reduced aggregates and restored memory). (家)

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Important caveats

• All causal efficacy is in mice. Human benefit is unproven; EMR signals are observational and subject to confounding. (家)
• Oncology dosing/toxicity: these drugs carry notable risks at cancer doses; the Cell work did not establish safe/effective human AD dosing. (The authors present a repurposing rationale based on transcriptomic reversal, not classical target-based AD mechanisms.) (考研)

Letrozole

Irinotecan