Seems like NAD boosters (NMN, NR, etc.) may not be so helpful in the quest to maintain brain function and cardiovascular health (though I’m unsure of the influence of the APOE knockout status of the mice used in the study and how that translates to human issues).
Open access paper:
https://www.atherosclerosis-journal.com/article/S0021-9150(25)00086-3/fulltext
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The general increase in inflammatory markers is a more broader concern of NR supplementation and one would assume this would apply for NMN as well.
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Charles Brenner has (unsurprisingly) waded in on this.
https://www.twitter.com/CharlesMBrenner/status/1910526936662552764
“obviously 8 completed human clinical trials showing anti-inflammatory effects of NR in ppl are more convincing than an experiment in a mutant mouse strain”
It is all part of this question as to whether you can have two much of a B3 vitamer, whether this relates to all of them or only a limited subset.
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Beth
#671
Just sharing what arrived in my inbox.
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Blood Tests: Not Just for the Impaired?
In memory clinics and in research cohorts, immunoassays for plasma markers can now distinguish people who have Alzheimer’s disease pathology with remarkable accuracy (see Part 7 of this series). How about in the general population? Could these tests catch people in the early stages of AD, before they turn up at their doctor with memory concerns?
What did they find? Schöll shared some hot-off-the-press data. “We’ve only had it a few days, so it is very preliminary,” he told the audience in Vienna. Still, some patterns may be emerging. The neotiv neotiv | Enabling cognitive health cognitive test appears to correlate with age, with older people scoring lower. Men performed worse than women across all ages; though the difference was slight, it was consistent, said Schöll.
Intriguingly, plasma p-tau217 rose with age, and more so among people who tested positive for amyloid. This was slightly different than Sebastian Palmqvist, Lund University, reported for primary care settings. There too, the marker inched up with age in people who were amyloid-negative, but the opposite was true among the amyloid-positives (see Part 7 of this series). In REAL AD, baseline numbers were slightly higher in people who carried an ApoE4 allele.
https://www.alzforum.org/news/conference-coverage/blood-tests-not-just-impaired
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Curious
#675
Of course, the body is connected. I have always thought that the connection between the skin and the brain, its signals and our emotional state is overlooked. There is an obvious connection. (almost like the gut brain axis). .Just think how some people are prone to blushing.
The skin and brain develop together during embryogenesis and share a close developmental relationship, particularly in the early stages.
Both the skin (epidermis) and the nervous system (brain, spinal cord, and peripheral nerves) has a common origin and rise from the ectoderm, the outermost germ layer of the embryo.
In early in development, the ectoderm differentiates into.
- Neuroectoderm , which forms the neural tube (future brain and spinal cord) and neural crest cells (which contribute to peripheral nerves, melanocytes, and other structures).
- Surface ectoderm which forms the epidermis, hair, nails, and sweat glands.
Neural Crest Cells Contribute to Both Systems. The neural crest (a transient, multipotent cell population) gives rise to.
- Melanocytes (skin pigmentation).
- Sensory neurons in the skin (connecting skin to the brain).
- Parts of the peripheral nervous system (which communicates with the brain).
Key molecular signals (e.g., Wnt, BMP, FGF) regulate both neurogenesis (brain development) and epidermal differentiation.
There is the obvious functional Connection Later in Development and the skin and brain remain linked through the somatosensory system. When sensory receptors in the skin (touch, pain, temperature) send signals via peripheral nerves to the brain. We know that touching can elicit oxytocin, which affects our mood. The brain processes constantly signals from the skin and generates responses like pulling away from pain. And we see how the brain is affected by chronic pain.
While the skin and brain arise from the same germ layer (ectoderm) and share early developmental signals, they diverge into distinct systems. Their embryological connection explains why some genetic disorders like neurocutaneous syndromes like Neurofibromatosis which affect both the skin and nervous system.
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Midlife lipid and glucose levels are associated with Alzheimer’s disease
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12641
Quote:
"## Abstract
Introduction
It is unknown whether vascular and metabolic diseases assessed in early adulthood are associated with Alzheimer’s disease (AD) later in life.
Methods
Association of AD with lipid fractions, glucose, blood pressure, body mass index (BMI), and smoking obtained prospectively from 4932 Framingham Heart Study (FHS) participants across nine quadrennial examinations was evaluated using Cox proportional hazard and Kaplan-Meier models. Age-, sex-, and education-adjusted models were tested for each factor measured at each exam and within three adult age groups (early = 35-50, middle = 51-60, and late = 61-70).
Results
A 15 mg/dL increase in high density lipoprotein (HDL) cholesterol was associated with decreased AD risk during early (15.4%, P = 0.041) and middle (17.9%, P = 0.014) adulthood. A 15 mg/dL increase in glucose measured during middle adulthood was associated with 14.5% increased AD risk (P = 0.00029). These findings remained significant after adjusting for treatment.
Discussion
Our findings suggest that careful management of cholesterol and glucose beginning in early adulthood can lower AD risk."
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I have been able to get my omega index to 10% eating sardines or salmon everyday. Without supplementing.
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How much (ounces or grams) of salmon and sardines per day to you consume?
I eat either 84 to160 grams of sardines or 6 ounces of sockeye salmon. Some days I eat 2 tins of sardines for lunch.
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Neo
#681
@Kytexas
Wow, cool.
Have you assessed your heavy metal levels?
I have had my blood tested for heavy metals including mercury and I have zero amount detected by Labcorp. I have ate the same brands of sardines and salmon for last 6 years. No other brands.
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Summary: New research reveals a striking gap between people’s theoretical desire to know their Alzheimer’s disease risk and their real-life decisions when results are actually offered. In a study of cognitively normal volunteers, only 60% chose to learn their estimated risk when given the chance, despite 81% expressing prior interest.
Concerns about anxiety, burden on family, and the lack of effective treatments were major reasons for declining results. The findings highlight the ethical and psychological complexities of sharing predictive health information and stress the importance of offering participants genuine choice without pressure.
Key Facts:
-
Interest vs. Action Gap: Only 60% of participants chose to receive their Alzheimer’s risk despite 81% expressing earlier interest.
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Emotional Burden a Key Factor: Common reasons for declining included fear of anxiety and the absence of treatment options.
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Need for Sensitive Approaches: Findings emphasize designing studies that respect participants’ right to decline risk information
Open Access Paper:
Research Participant Interest in Learning Results of Biomarker Tests for Alzheimer Disease
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2833583
and
Results from the study show that participants who don’t have amyloid buildup experienced significant emotional improvements: They reported much lower levels of depression, anxiety and memory complaints.
However, their motivation to maintain lifestyle improvements also declined.
Conversely, participants with amyloid presence didn’t show increased depression or memory complaints but did experience a decrease in anxiety and motivation for lifestyle adjustments.
“The findings suggest that disclosing amyloid presence does not negatively affect participants, and simply knowing the results seems to decrease negative feelings overall,” said Schnaider Beeri.
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USF Health researchers developing probiotic cocktail that may help ward off dementia
His team’s findings about the probiotic cocktail, published in Nature Scientific Reports in January, suggests that the concoction could become a novel therapy to help lower the risk of Alzheimer’s disease and other forms of dementia. While the research has many further steps of testing to see whether the cocktail lives up to its potential, it proposes a different approach to preventing dementia. Existing medications for Alzheimer’s disease target biological mechanisms in the brain, not the gut.
In the study, Protection of Alzheimer’s disease progression by a human-origin probiotics cocktail, Dr. Yadav and his team described developing the cocktail, which contains multiple kinds of probiotics, or strains of “good” bacteria known to help keep the human gut working as it should. Study mice received the cocktail in their drinking water for 16 weeks and then performed a “water maze” test, in which they are given visual cues to help them swim to a hidden underwater platform. Cocktail-drinking mice were consistently able to find the platform faster.
Dr. Yadav’s team found that the cocktail reduced the levels of proteins that can cause the build-up of sticky plaques in the brain. It also appeared to lower levels of brain inflammation and preserve tight junctions in the blood-brain barrier — preventing leakage of harmful microorganisms into the brain. The results suggest that this probiotics mixture could decrease the progression of cognitive decline and Alzheimer’s disease.
Open access paper:
Protection of Alzheimer’s disease progression by a human-origin probiotics cocktail
Herein, we tested a cocktail of unique probiotics, including 5 Lactobacillus and 5 Enterococcus strains isolated from infant gut with proven microbiome modulating capabilities. We aimed to determine the probiotics cocktail’s efficacy in ameliorating AD pathology in a humanized AD mouse model of APP/PS1 strains. Remarkably, feeding mice with 1 × 1011 CFU per day in drinking water for 16 weeks significantly reduced cognitive decline (measured by the Morris Water Maze test) and AD pathology markers, such as Aβ aggregation, microglia activation, neuroinflammation, and preserved blood-brain barrier (BBB) tight junctions. The beneficial effects were linked to a reduced inflammatory microbiome, leading to decreased gut permeability and inflammation in both systemic circulation and the brain. Although both male and female mice showed overall improvements in cognition and biological markers, females did not exhibit improvements in specific markers related to inflammation and barrier permeability, suggesting that the underlying mechanisms may differ depending on sex. In conclusion, our results suggest that this unique probiotics cocktail could serve as a prophylactic agent to reduce the progression of cognitive decline and AD pathology. This is achieved by beneficially modulating the microbiome, improving intestinal tight junction proteins, reducing permeability in both gut and BBB, and decreasing inflammation in the gut, blood circulation, and brain, ultimately mitigating AD pathology and cognitive decline.
https://www.nature.com/articles/s41598-024-84780-8
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It’s interesting that even knowing you’re at higher risk, motivation to maintain healthy habits fades over time. I guess people figure, “fark it, too much work”.
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Neo
#686
And if I understand it right @CronosTempi @RapAdmin
know either that at increases or decreases BOTH lead to less motivation to take actions?
Vitamin B12 Levels May Be Set Too Low to Prevent Cognitive Decline in Older Adults
A recent study published in the Annals of Neurology on February 10, 2025, suggests that levels of vitamin B12 considered within lab-normal values may be too low to prevent cognitive decline in healthy older adults [1].
Findings of the Study
The study was led by researchers at the University of California, San Francisco (UCSF) who investigated whether vitamin B12 levels, despite falling within the lab normal range, might still be associated with neurological damage or impaired function in healthy older adults [1].
The study included 231 healthy individuals, all without dementia or mild cognitive impairment, who were recruited from the Brain Aging Network for Cognitive Health (BrANCH) at UCSF. Participants had an average age of 71, with a median blood vitamin B12 concentration of approximately 414.8 pmol/L.
- Beaudry-Richard, A., Abdelhak, A., Saloner, R., et al (2025), Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults. Ann Neurol. https://doi.org/10.1002/ana.27200
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