I tend to think of low dose as resulting in 0.05mM serum levels or lower. Sadly below the minimum threshold of my lab.
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Diet Quality and Dementia Risk in Older Adults With Alzheimer Pathology
Pop-sci article:
Anti-inflammatory diets may lower dementia risk, even in those with early signs
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Higher blood glucose levels linked to faster brain aging
Faster brain aging has been linked to various neurological and psychiatric disorders, as well as some neurodegenerative diseases. The factors that influence the speed at which the brain ages, however, have not yet been clearly and comprehensively elucidated.
Researchers at Jilin University and China Medical University recently analyzed available neuroimaging, genomic and biological data to better understand the contribution of metabolic processes (i.e., the chemical reactions that transform food into energy) to brain aging. Their findings, published in Molecular Psychiatry, suggest that higher levels of glucose in the blood are associated with accelerated brain aging.
Uncovering metabolic signatures of brain aging with AI
To explore the biological underpinnings of brain aging, the researchers analyzed data from the UK Biobank, a large biomedical database that contains health-related, genetic and imaging data collected from thousands of people living in the U.K. By analyzing these peopleās brain scans, they derived measurable brain features, such as the size of specific brain regions, tissue characteristics and structural changes.
Subsequently, they trained machine learning algorithms to predict the age of people based on the brain features they identified. They found that a specific statistical method, known as a least absolute shrinkage and selection operator (LASSO) regression model, was best at predicting the age of peopleās brains, with an average error rate of 3.26 years.
https://medicalxpress.com/news/2026-07-higher-blood-glucose-linked-faster.html
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Diabetes (SGLT2) drug tied to lower dementia risk
Unexpected benefit: SGLT2 inhibitors, used for diabetes, were linked to reduced dementia risk in psychiatric patients.
High-risk focus: Older adults with mood or psychotic disorders face higher dementia rates, but few prevention options.
Future implications: Researchers call for more trials to confirm benefits and explore metabolic-brain health connections.
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How dementia is being defeated
Incidence among the elderly is falling fast
Mr Stallard has been working for a decade to corroborate this revelation. His findings have, if anything, become even more striking. Last year he and some colleagues published research in the Journal of the American Medical Association showing that, whereas 40 years ago three in every ten Americans aged 85-89 had dementia, by 2024 just one in ten had it (see chart 1). What is more, America is not the only beneficiary of this trend. Between 1988 and 2015 the share of older people being diagnosed with dementia fell by 13% a decade across six countries in North America and Europe, according to a study of almost 50,000 people by Frank Wolters of the Erasmus Medical Centre in Rotterdam, and colleagues.
chart: the economist
Some smaller studies have also found big declines. Data from the Framingham Heart Study, which has tracked three generations in an American town, show an average drop in new dementia cases of 20% per decade over almost 40 years between the late 1970s and early 2010s. Those who were entering their dotage when Daft Punkās āGet Luckyā was topping the charts (2013) were 44% less likely to have dementia than those who were doing so when Sting was urging Roxanne to switch off her red light (1978).
Whereas most earlier studies had simply pooled elderly people and then applied a statistical adjustment for age, Mr Stallard looked at narrow bands of ages to compare different cohorts of people over 50 years. By examining the changes between each successive cohort, he calculates that dementia rates have been declining by 2.5-3% for each calendar-year cohort. āIn my view it was the Copernican revolution in the field,ā he says, turning assumptions about dementiaās spread upside down. Similar cohort studies in various European countries and Japan have found comparable trends there, too.
Full story: How dementia is being defeated (The Economist)
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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 Alzheimerās-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 Alzheimerās disease and other signs of damage or stress in the brain. They also assessed participantsā diets, lifestyle habits and health status, updating this information at follow-up visits three and six years later.
Participantsā 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 personās 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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Apparently:
Inhaling high-dose CO2 clears Alzheimerās proteins from the brain
Intermittently inhaling a high dose of carbon dioxide seems to remove the proteins amyloid and tau, which are implicated in Alzheimerās disease, from the brain by boosting its glymphatic system.
If it doesnāt kill you first.
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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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Guanfacine may aid in improving sleep caused by amyloid beta induced disruption of Alzheimerās disease: ā5xFAD 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 (AĪ²)-induced disruption of Ī±2A adrenergic receptor regulation. Pharmacological activation of Ī±2A adrenergic receptors restored Kv4/7 function and normalized LC excitability. Local administration of guanfacine (Ī±2A agonist) or retigabine (Kv7 modulator) significantly rescued sleep-wake disturbances.ā Impaired adrenergic regulation of Kv channels underlies LC hyperactivity and early-onset sleep disruption in AD-like amyloidogenic mice pubmed.ncbi.nlm.nih.gov
Crossposting:
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Alzheimerās may start with inflammation in the skin, lungs or gut
The Alzheimerās 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
Alzheimerās 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 ā perhaps decades before a personās memory starts to decline. This radical reframing of the disease may explain why Alzheimerās 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.
āAs 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,ā says Donna Wilcock at Indiana University, who wasnāt involved in the research. āEven though Alzheimerās is a brain disease, we need to think about the whole body when we think about how it begins.ā
To explore the genetic underpinnings of Alzheimerās disease, CĆ©sar 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 Alzheimerās 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. āI kept looking at the graph and it seemed wrong because the expression of these genes in single cells in the brain was extremely low,ā says Cunha. āBut we ran more analyses and the more we looked at it, the more we realised they really werenāt in the brain, they were mostly in other parts of the body.ā
Full article: Alzheimerās may start with inflammation in the skin, lungs or gut (New Scientist)
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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 Alzheimerās. Those agents might act against inflammatory and other pathological processes in those tissues where AD might have etiological triggers. Food for thought - literallyā¦ 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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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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Orexin and Alzheimerās: Exploring the Sleep Connection
Alzheimerās 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 Alzheimerās. 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 Alzheimerās disease interact.
Source Research Paper:
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 ā increase soluble beta amyloid from CSF to blood.
So yes, youāll 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 youāll 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, couldnāt sleep, really wiped out after - could 30 minutes of cyclic hypercapnia get you restored as though youād have deep sleep?
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