Predicting and Preventing Alzheimers & Dementia (and minimizing risk)

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#1102

An anti-inflammatory diet may prevent dementia, even in people at higher risk, new study suggests

About the latest research

The new study, published in June in JAMA Network Open, sought to determine whether healthy eating patterns could modify dementia risk in older adults with blood biomarkers indicating Alzheimer’s-related brain changes or other signs of brain cell damage.

To do so, the researchers analyzed data from adults without dementia, ages 60 and older, who took part in the Swedish National Study on Aging and Care. A total of 1,865 participants, with an average age of 70, were followed for up to 15 years.

At the start of the study, researchers measured three blood biomarkers linked to Alzheimer’s disease and other signs of damage or stress in the brain. They also assessed participants’ diets, lifestyle habits and health status, updating this information at follow-up visits three and six years later.

Participants’ diet information was used to assess adherence to three dietary patterns: a Mediterranean-style diet, the Alternative Healthy Eating Index and the Reverse Empirical Dietary Inflammatory Index, which measures the inflammatory potential of a person’s diet (a higher score denotes a more anti-inflammatory diet). Higher adherence scores for each dietary pattern indicate a higher quality diet.

Each diet pattern highlights different aspects of diet quality, and they all emphasize vegetables, fruits, nuts and whole grains while limiting more inflammatory foods such as red and processed meats and sugary drinks.

Better diets, especially less inflammatory ones, tied to lower dementia risk

Across all participants, healthier diet patterns were associated with a lower likelihood of developing dementia.

When the researchers analyzed participants according to their levels of blood biomarkers, however, they found striking results.

Greater adherence to all three diet patterns was generally associated with a lower risk of dementia among people with lower levels of blood biomarkers.

Full article: An anti-inflammatory diet may prevent dementia, even in people at higher risk, new study suggests

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#1103

Apparently:

Inhaling high-dose CO2 clears Alzheimer’s proteins from the brain

Intermittently inhaling a high dose of carbon dioxide seems to remove the proteins amyloid and tau, which are implicated in Alzheimer’s disease, from the brain by boosting its glymphatic system.

If it doesn’t kill you first.

Study

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#1104

For mind and body: Community gathering places may counteract cognitive disability

Effect Modification by Exercise Habit on the Association Between Participation in Community Gathering Places and Cognitive Disability

https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.70499

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#1105

Guanfacine may aid in improving sleep caused by amyloid beta induced disruption of Alzheimer’s disease: “5xFAD mice displayed dark phase-specific hyperarousal and impaired brain state transitions by 2 months of age. LC neurons exhibited increased tonic firing due to impaired Kv4 and Kv7 potassium channel conductance, resulting from soluble amyloid beta (Aβ)-induced disruption of α2A adrenergic receptor regulation. Pharmacological activation of α2A adrenergic receptors restored Kv4/7 function and normalized LC excitability. Local administration of guanfacine (α2A agonist) or retigabine (Kv7 modulator) significantly rescued sleep-wake disturbances.” Impaired adrenergic regulation of Kv channels underlies LC hyperactivity and early-onset sleep disruption in AD-like amyloidogenic mice pubmed.ncbi.nlm.nih.gov

#1106

Crossposting:

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#1107

Alzheimer’s may start with inflammation in the skin, lungs or gut

The Alzheimer’s field is being turned on its head as mounting evidence points to the disease beginning outside the brain many years before symptoms start. This may mean we have to totally rethink how we approach preventing and treating the condition

Alzheimer’s disease has long been viewed as something that originates inside the brain, but an in-depth genomic analysis suggests it may initially be triggered by inflammation in distant organs like the skin, lungs or gut – perhaps decades before a person’s memory starts to decline. This radical reframing of the disease may explain why Alzheimer’s drugs have been disappointing to date, because they act too late in the disease process. Instead, we may need to redirect our efforts towards addressing inflammation in other parts of the body.

“As neuroscientists, we tend to be very brain-centric, but this study really shines a spotlight on the fact that the brain is not disconnected from the rest of the body, and when changes happen in the rest of the body, it affects how the brain functions,” says Donna Wilcock at Indiana University, who wasn’t involved in the research. “Even though Alzheimer’s is a brain disease, we need to think about the whole body when we think about how it begins.”

To explore the genetic underpinnings of Alzheimer’s disease, César Cunha at the Novo Nordisk Foundation Center for Basic Metabolic Research in Denmark and his colleagues studied genetic data from more than 85,000 people with the condition and 485,000 people without it from the European Alzheimer and Dementia Biobank. They also analysed gene activity in 5 million single cells from 40 areas of the body and 100 brain regions.

As part of this deep dive, the researchers examined 1000 genes with variants that increase the risk of Alzheimer’s disease. To their surprise, these seemed to show up far less in the brain than in other organs like the skin, lungs, digestive system and spleen, as well as in various types of immune cells circulating in the blood. “I kept looking at the graph and it seemed wrong because the expression of these genes in single cells in the brain was extremely low,” says Cunha. “But we ran more analyses and the more we looked at it, the more we realised they really weren’t in the brain, they were mostly in other parts of the body.”

Full article: Alzheimer’s may start with inflammation in the skin, lungs or gut (New Scientist)

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#1108

If so, then this might explain, at least in part, the persistent findings that agents which do not cross the BBB or barely do, (like rapamycin), nonetheless often seem very impactful in various brain NDDs including dementias like Alzheimer’s. Those agents might act against inflammatory and other pathological processes in those tissues where AD might have etiological triggers. Food for thought - literally… if we posit that diet is associated with dementia, it need not affect the brain directly, just through a proxy like gut microbiome. It might all be connected, the body being an interconnected biological system.

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#1109

This also keeps GLP1s very much in play, even with the disapointing results from the Novo trial that showed semaglutide did not slow down the disease once it set.

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#1110

Orexin and Alzheimer’s: Exploring the Sleep Connection

Alzheimer’s is a progressive brain disorder, and sleep disruption is a well-known feature of the condition. In a study of 60 people with the disease, higher levels of orexin in cerebrospinal fluid were associated with faster cognitive decline. Yet strong brain-wave activity during deep sleep appeared to weaken that connection. The authors stress that the findings are not proof of cause and effect and that larger studies are needed.

All participants were over age 60 and had mild or moderate Alzheimer’s. Each person spent one night in a sleep laboratory, and cerebrospinal fluid samples were collected the next morning. Over the following three years, those with higher orexin levels showed a quicker worsening of symptoms.

Brain Activity During NREM Sleep: A Closer Look

When researchers analyzed NREM sleep, they found that stronger sleep spindles and slow oscillations reduced the link between orexin and decline. Participants with more pronounced versions of these brain rhythms exhibited a much weaker association. Lower orexin levels also matched up with denser sleep spindles and longer slow oscillations.

Notably, orexin concentrations in cerebrospinal fluid were higher in women than in men. Still, the authors point out that the results cannot prove causality, and the lack of a healthy control group limits broader conclusions. The three-year pattern was inferred from just one night of sleep recording and a single cerebrospinal fluid sample.

Going forward, the team stresses the need for larger trials with more participants, more detailed sleep monitoring, and healthy controls to better understand how orexin, sleep, and Alzheimer’s disease interact.

Source Research Paper:

Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience

https://www.neurology.org/doi/10.1212/WNL.0000000000218307

#1111

@adssx @DrFraser any thoughts on this?

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#1112

Hypercapnea (increased PaCO2) is a strong global vasodilator.
Done intermittently, it creates slow waves of vasodilation/vasoconstriction = vasomotion. This ends up being coupled to stimulating CSF movement = enhanced glymphatic/pervascular clearance → increase soluble beta amyloid from CSF to blood.
So yes, you’ll get higher blood levels after hypercapnea, especially with deep rhythmic breathing (to blow of the the CO2 in recovery) as that seems to further stimulated CSF flow.
The big question is whether clearing some of the soluble amyloid from your CSF makes any difference to the brain that is infiltrated with it?
The diseased brain remains, but yet you’ll move some of the soluble aspect of beta amyloid out into your blood stream.
Jon Brudvig PhD and I are doing a video on this exact topic, part 1 will publish in the next week. Part 2 will be me hooked up to an oximeter/capnography and testing some breathing techniques that would best generate cyclic hypercapnia and showing the data as we go.
The unknown is does this in anyway reduce brain amyloid burden?
I think the other fascinating discussion point on this, is whether this could be a mimetic of deep sleep. For example, if you were doing an international flight, couldn’t sleep, really wiped out after - could 30 minutes of cyclic hypercapnia get you restored as though you’d have deep sleep?

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#1113

As usual and truly amazing reply @DrFraser

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#1114

The dementia that often strikes in midlife — and the signs people miss

Initial symptoms of frontotemporal dementia (FTD) are easy to miss, since they can look more like a psychiatric condition than a neurodegenerative one.

September 4, 2026 at 6:00 a.m. EDT

If you’ve heard of frontotemporal dementia (FTD), it may be because of Bruce Willis or Wendy Williams — two celebrities whose diagnoses in recent years have shed light on this infrequently discussed neurodegenerative disease. Though FTD is relatively rare, accounting for about 5 percent to 10 percent of all dementia cases and affecting an estimated 50,000 to 60,000 people in the United States, it’s the most common form of early-onset dementia.

In fact, 60 percent of people who get diagnosed with it are ages 45 to 64, decades younger than the average person diagnosed with Alzheimer’s disease (which causes most cases of dementia). And yet, experts believe this is a significant undercount because it’s “rare enough that most medical providers, even specialists, don’t have experience with it, and so they don’t know what it looks like,” said Brad Dickerson, neurologist at the Mass General Brigham Neuroscience Institute and director of the Frontotemporal Disorders Unit at Massachusetts General Hospital.

The initial symptoms of FTD also diverge sharply from those of the more common Alzheimer’s disease because of the parts of the brain it attacks. FTD often starts “in the front of the brain, which is very important for behavior, regulation of social interactions, addiction, drive, organizing and planning,” said Bruce Miller, a professor of neurology and director of the Edward and Pearl Fein Memory and Aging Center at the University of California at San Francisco.

So, FTD generally manifests first with behavior or mood changes — rather than the memory loss and thinking problems of Alzheimer’s (which typically first affects the areas of the brain responsible for these tasks, including the hippocampus). It’s the reason FTD is often misread as a psychiatric issue, Miller said. On average, it takes about three to four years for people to get a diagnosis of FTD, according to the Association for Frontotemporal Degeneration.

Below, experts explain why FTD tends to hit earlier in life than other dementias, the often-overlooked signs to know and what care for people with the condition looks like.

FTD most often begins in the frontal lobe and its earliest symptoms typically include behavior or personality changes — called behavioral-variant FTD. The most common ones are easily mistaken as signs of psychiatric conditions such as depression or bipolar disorder, or dismissed as the effects of stress, burnout or even a midlife crisis. They include:

  • Apathy. “People lose interest in doing things, they move less and they are less interested in the stories of loved ones,” Miller said.
  • Addictive behaviors. They might turn to compulsive drinking, drugs, sex or several of the above, Miller pointed out.
  • Loss of empathy. People with FTD tend to become alienated from their partners, children, friends and co-workers — and a big reason for that is losing the ability to feel what others are feeling, Miller said.
  • Difficulty with planning, organizing and managing money. FTD often hinders executive function, which refers to high-level cognitive skills including problem-solving, abstract thinking, regulating sensory input and decision-making. One way this could manifest: Dickerson said he’s seen many patients who have fallen victim to scams that might have seemed obviously problematic to someone without FTD.
  • Disinhibition. FTD can cause people to lose their filter or start acting in ways that are socially inappropriate, Dickerson said. He gave the example of someone urinating in a public bathroom without closing the door behind them.

Read the full story: The dementia that often strikes in midlife — and the signs people miss

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#1115

Fibronectin mediates APOE4-driven blood–brain barrier dysfunction in Alzheimer’s disease

Source: Fibronectin mediates APOE4-driven blood–brain barrier dysfunction in Alzheimer’s disease | Nature Aging

Conclusion from study:

“Despite the robust findings in this study, we note some limitations. To further enhance the applicability of these findings to human AD, validation can be conducted in additional human brains and in reductionist models of the human vascular niche. Furthermore, the known overlap of other comorbidities, such as diabetes and hypertension, could contribute to the observed relationships among fibronectin, VEGFA, HB-EGF, IGF-1 and AD pathology. Although we identified inflammation as one driver of fibronectin deposition, the specific inflammatory signals and their roles at different stages of the disease require further investigation. While this study establishes fibronectin as a mechanistic mediator of BBB dysfunction, the consequences of this pathway for cognition and higher-order brain function were not directly assessed and remain an important area for future investigation.”

GPT summary:

"The researchers identify an ECM component as a causal mediator of pathology and then partially reverse the pathology by manipulating it, which is much closer to the kind of ECM work we’ve been waiting for. Nature

The protein is fibronectin (FN1), an extracellular matrix glycoprotein. The researchers connect APOE4 to abnormal fibronectin accumulation around the brain vasculature:

APOE4 / amyloid / inflammation → astrocytes produce excess fibronectin → abnormal perivascular ECM deposition → disrupted integrin/FAK signalling → impaired VEGF, HB-EGF and IGF-1 signalling → blood-brain barrier dysfunction. Nature

That chain is supported unusually thoroughly. They combine human postmortem brain tissue, CSF and plasma data, single-cell transcriptomics, human iPSC-derived astrocytes, 3D human vascular models, zebrafish and aged mouse models. In 21 to 22-month-old APOE4 knock-in mice, brain fibronectin was almost double that of APOE3 animals. Nature

The intervention experiments are what push this over the line for me. Reducing fibronectin restored BBB integrity, and independently restoring the growth-factor signalling suppressed by excess fibronectin also rescued BBB function in experimental models. So the ECM alteration is not merely correlated with the disease state. Nature

There is also a fascinating human-genetics clue behind the whole project. Previous work identified a rare loss-of-function FN1 variant associated with a 71% reduction in Alzheimer’s risk among APOE4 carriers. The new study provides a plausible mechanistic explanation for why reducing fibronectin activity might be protective. Nature

Why I think it’s especially worth your time

This gets at something broader than Alzheimer’s.

Fibronectin is normally useful. It is an important part of wound healing and ECM remodeling. The problem appears to be excessive or misplaced deposition of an otherwise useful matrix protein, which then alters how neighboring cells behave.

That is exactly the sort of feedback relationship that makes ECM aging interesting. Aging cells remodel the matrix, but the remodeled matrix can subsequently alter signalling, vascular function, inflammation and cellular behavior. The ECM therefore stops looking like passive scaffolding and starts looking like another information-bearing component of the aged tissue environment.

The authors explicitly connect pathological fibronectin accumulation with broader vascular basement-membrane remodeling, impaired metabolic-waste clearance and neuroinflammation. They also note that the protective FN1 variant has been associated with reduced Lewy body disease risk, raising the possibility that this mechanism extends beyond Alzheimer’s. Nature

There are important limitations. They have not demonstrated that lowering fibronectin prevents dementia in humans, cognition was not directly tested in the experimental intervention, and several authors have patents related to FN1-targeted therapies and are founders/shareholders of KVM Therapeutics. Those conflicts are disclosed in the paper."

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#1116

The preliminary analysis, published in Nature Metabolism, finds initial evidence that a popular supplement, taken by more than 40 million Americans, is associated with faster progression to dementia in people with early memory problems.

Glucosamine is a natural sugar-related molecule widely sold over the counter as a supplement in the US.

It is especially popular among older adults, who use it to support joint health and manage arthritis symptoms or joint discomfort.

But it may have an insidious downside for a certain subset of older adults.

Using electronic health record data, researchers at the University of Florida (UF) have now found that glucosamine use was associated with a 25 percent higher likelihood that mild cognitive impairment would progress to dementia.

“People take the supplement based on anecdotal reports that it improves joint health, especially in the knees,” writes biochemist Ramon Sun from UF for The Conversation.

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#1117

Lemborexant ameliorates tau-mediated sleep loss and neurodegeneration in males in a mouse model of tauopathy

https://www.nature.com/articles/s41593-025-01966-7

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#1118

Also, it’s almost worthless for its intended use. IMO benefits obtained are mostly placebo.

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#1119

There’s already been a thread opened about this some time ago with a discussion. Maybe they can be merged.

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#1120

Nothing conclusive in here … just a theory about head shape

https://www.nytimes.com/2026/10/22/science/alzheimers-disease-brain-head-shape.html?unlocked_article_code=1.KlE.IsLX.by_D6IBvDbzJ&smid=nytcore-ios-share
Gifted article

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#1121

Those hotel beds (from long ago) that vibrate when you put a quarter in, are going to come back into style :smile:

Vibrating mattress helps clear Alzheimer’s protein from the brain

Lying on a vibrating mattress while taking nitric oxide pills has shown promise for boosting the brain’s waste-disposal system. It caused the brain’s blood vessels to swell and constrict more strongly, which enhanced the glymphatic system’s clearance of a protein that accumulates during Alzheimer’s disease.

Other experiments into boosting the glymphatic system have involved ultrasound, pink noise and even intermittently inhaling high doses of carbon dioxide. “It’s important to come at this from as many angles as possible, to increase the chance of this translating to the clinic and benefitting patients,” says Christopher Brown at the University of Southampton, UK, who wasn’t involved in the latest research.

But risky experimental approaches like taking nitric oxide and inhaling carbon dioxide shouldn’t be tried at home, says Vesa Kiviniemi at the University of Oulu in Finland. Regarding the latest experiment, which he led, Kiviniemi points out that “nitric oxide can reduce blood pressure, and if one happens to have low blood pressure to begin with, taking a pill might lead to loss of consciousness”.

Prior studies in mice have shown that vibrating the body activates a motion-sensitive protein called Piezo1, which is found in muscle cells in the walls of the brain’s blood vessels. This causes the vessels to dilate and constrict more strongly, which helps push waste fluid from brain cells through the glymphatic system, a network of channels that surrounds blood vessels in the brain and transports waste for disposal elsewhere in the body.

Other research has shown that nitric oxide, which is naturally produced in the brain, also dilates its blood vessels. This seems to make the surrounding glymphatic channels narrower, putting more pressure on the waste fluid so it exits the brain more quickly, says Kiviniemi.

Read the full article: Vibrating mattress helps clear Alzheimer’s protein from the brain (New Scientist)

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A Heart Pill and a Vibrating Mattress May Clear Alzheimer’s Protein From The Brain