Just received some ACD856 and I’ve taken my first dose. I will be trialling this short term to see how it goes.
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@adssx I’ve been planning to make P7C3-A20, so if other people are interested I could have some in ~3-4 weeks. In-house confirmation with LC-MS and 3rd-party quantitation w/ qNMR.
P7C3-A20 has also been tested in primates and shown to promote survival of nascent hippocampal neurons without affecting proliferation. I’d speculate that for long-term function this mechanism is safer than proliferative mechanisms (e.g NSI-189) that may accelerate neural stem cell exhaustion.
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Obesity and high blood pressure may directly cause dementia
The findings highlight weight and blood pressure control as potentially powerful tools for preventing dementia before symptoms appear.
A new genetic study suggests that obesity and high blood pressure may play a direct role in causing dementia, not just increasing the risk. By analyzing data from large populations in Denmark and the U.K., researchers found strong evidence that higher body weight can damage brain health over time, especially when it leads to elevated blood pressure. Much of the dementia risk appeared to be tied to vascular damage in the brain, which affects blood flow and cognitive function.
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Interesting mechanistic insight into the neuroprotection afforded by ApoE2/ApoE3Ch relative to ApoE4:
• ApoE2 and ApoE3Ch reduce neuronal ferroptosis by oxidized lipid efflux via ABCA7
• Lysosomal defects caused by lipid peroxidation are rescued by ApoE2 and ApoE3Ch
• ApoE2 and ApoE3Ch particles protect ApoE4 hippocampi from toxicity
• ApoE2 and ApoE3Ch particles rescue ApoE4 neural activity from excitotoxicity
Summary
Apolipoprotein E (ApoE) mediates the bidirectional transport of lipids between cells. In the brain, this includes the transfer of lipids from neurons to glia. ApoE4, a major risk factor for Alzheimer’s disease, impairs this transport pathway, increasing risk for neurodegeneration. ApoE2 and ApoE3 Christchurch (ApoE3Ch) confer resistance to disease, yet little is known regarding how these variants affect lipid trafficking. Here, we explored how lipoprotein particles containing different ApoE isoforms affect neuronal health. We demonstrate that ApoE2 and ApoE3Ch particles protect neurons from ferroptosis by extracting oxidized unsaturated lipids through the ABCA7 transporter. ApoE4 particles, on the other hand, exacerbate the effects of these toxic lipids, leading to endolysosomal dysfunction. By reducing the oxidized lipid burden in ApoE4 neurons, ApoE2 and ApoE3Ch particles rescue endolysosomal function and restore defects in neuronal activity caused by excitotoxicity. Our findings reveal how ApoE2 and ApoE3Ch help protect neurons from neurodegeneration.
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Beginning in the late 1990s, nearly 3,000 older adults received brain training as part of a study to evaluate the training’s effect on thinking and memory. Twenty years later, participants continued to reap the benefits.
In the latest follow-up from the Advanced Cognitive Training for Independent and Vital Elderly, or ACTIVE, study, investigators report that participants who received cognitive speed training, plus booster sessions one and three years later, were 25% less likely to be diagnosed with dementia in the next two decades.
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new study shows coffee is associated with improved cognition and reduced risk of dementia
Coffee and Tea Intake, Dementia Risk, and Cognitive Function
https://jamanetwork.com/journals/jama/article-abstract/2844764
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Based on the NBC News story and the clinical data from the ACTIVE study (Advanced Cognitive Training for Independent and Vital Elderly), the specific software and the criteria for the cognitive intervention are detailed below.
1. The Specific Game Referenced
The news story refers to a cognitive exercise originally known as “Speed of Processing” training. This specific iteration is commercially available as Double Decision.
- Game Name: Double Decision
- Platform: BrainHQ (by Posit Science)
- Scientific Validation: This specific software is the direct evolution of the “speed of processing” intervention used in the ACTIVE study. It was the only intervention (compared to memory and reasoning training) that demonstrated a statistically significant reduction (29%) in dementia risk over a 10-year period.
2. Criteria for “Speed Training” (UFOV)
To meet the criteria of the “speed training” described in the study, a program must specifically target Useful Field of View (UFOV). This is distinct from general “reaction time” games. The training must enforce:
- Divided Attention: Simultaneous identification of a central target (e.g., a car) and a peripheral target (e.g., a road sign).
- Processing Speed: The duration of the stimulus must decrease as the user improves, forcing the visual cortex to process information faster (often down to millisecond exposures).
- Eccentricity: The peripheral target must move further to the edges of vision to expand the functional field of view.
3. Other Programs Meeting the Criteria
While Double Decision is the clinical standard used in the research, other commercially available programs utilize the same specific UFOV mechanics and likely engage similar neural pathways.
-
Lumosity: The specific game Eagle Eye is designed to train the useful field of view.
- Mechanism: It requires the user to identify a central bird while simultaneously pinpointing the location of a second bird in the periphery. This mirrors the mechanics of Double Decision almost exactly.
- CogniFit: This platform offers specific Visual Field training and “Divided Attention” tasks that align with the ACTIVE study’s parameters.
Summary of Options
| Game / Program | Type | Connection to Research | Website |
|---|---|---|---|
| Double Decision | Clinical / Commercial | Direct Match. This is the exact software used in the ACTIVE study (via BrainHQ). | Link to Double Decision |
| Eagle Eye | Commercial | Likely Match. Explicitly targets “Useful Field of View” with identical central/peripheral mechanics. | Link to Lumosity |
| Action Video Games | Entertainment | Functional Match. Research indicates fast-paced FPS games (e.g., Call of Duty) improve UFOV, though they lack the structured adaptive algorithms of clinical tools. | N/A (Commercial Entertainment) |
Knowledge Gap & Academic Note
While Double Decision has the specific longitudinal data regarding dementia risk reduction (the ACTIVE study), it remains a subject of debate whether “likely match” games like Eagle Eye or general action video games confer the exact same long-term neuroprotective benefits without identical dosing and adaptive algorithms. Current consensus suggests the mechanism (UFOV expansion) is the key driver, implying other valid UFOV trainers should theoretically offer similar benefits, but direct comparative trials are limited.
What Makes BrainHQ Effective? The Science Behind the Exercises (2023)
The selected video provides an academic overview of the specific scientific principles behind the BrainHQ exercises, including the “speed of processing” mechanisms discussed in the ACTIVE study.
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Any thought on this? 300% improvement in memory of dementia patients sounds to good to be true.
Frankly, I think something like pickleball that involves movement coordination, visual acuity, speed and quick decision making provides exercise and is way more fun.
Also just playing video games like 3D shooters would have similar effects… and again way more fun.
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Of course it’s too good to be true, Aromatherapy has been around for a long time. I think most of the benefits are placebo. I have tried several different course of aromatherapy and did find any subjective or measureable results. IMO, it is mainly bs.
Common anti-seizure drug (levetiracetam) prevents Alzheimer’s plaques from forming, study shows
Now, in a new study, Northwestern University scientists have pinpointed when and where toxic proteins accumulate within the brains of Alzheimer’s patients—and discovered a decades-old Food and Drug Administration (FDA)-approved drug that can stop the accumulation process before it even begins.
By studying animal models, human neurons and brain tissue from high-risk patients, the team discovered a particularly toxic protein fragment, called amyloid-beta 42, accumulates inside neurons’ synaptic vesicles—the tiny packets that neurons use to send signals. But, when the scientists administered levetiracetam (an inexpensive, decades‑old anti‑seizure drug) to the animals and human neurons, the drug prevented neurons from forming amyloid-beta 42.
“While many of the Alzheimer’s drugs currently on the market, such as lecanemab and donanemab, are approved to clear existing amyloid plaques, we’ve identified this mechanism that prevents the production of the amyloid‑beta 42 peptides and amyloid plaques,” said corresponding author Jeffrey Savas, associate professor of behavioral neurology at Northwestern University Feinberg School of Medicine. “Our new results uncovered new biology while also opening doors for new drug targets.”
https://medicalxpress.com/news/2026-02-common-anti-seizure-drug-alzheimer.html
Paper:
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This article is behind a paywall and the press release is short on detail. This is the drug Keppra which was approved in the US in 1999. The journal it is published in has has an impact factor of 14.6.
Lots of studies out there with little to no effect on early AD in short trials. But I saw nothing on long term Keppra users compared to non Keppra seizure disorder users. That would be nice to know like the lithium studies. This article mentions a delay in death for AD patients taking Keppra compared to other anti convulsants but short on details in the press release. They mention small effect - but then say on the scale of a few years. That is small?
This is the first I am hearing about Keppra. And also the AGB101 studies - which is a proprietary low dose version from AGeneBio. It looks to me like they are trying hard to get FDA approval for something but not quite there yet.
Keppra is cheap and has liquid availability for micro dosing.
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In a dose for epilepsy the side effect of keppra can involve patients being very irritable and subject to outbursts of anger. I don’t know what would happen in microdosing.
I wouldn’t want to be on therapeutic lithium either. But, yeah, Keppra has some troubling SE at full dose.
Its perhaps more troubling for those people who live with people on Keppra.
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Does α-Amyrin Boost Autophagy, Thwart Tau Pathology?
People who consume copious fruits and vegetables tend to enjoy healthier, longer lives, and are less prone to dementia. How could noshing on plants ward off age-related diseases such as Alzheimer’s? According to a paper published on January 22 in Advanced Science, a bittersweet molecule called α-amyrin might be part of the answer. Found in numerous common fruits, including cranberries, pears, bell peppers, eggplants, tomatoes, grapes, cherries, passion fruits, and olives, this triterpenoid reportedly thwarts tau aggregation in cell culture and in mice. Led by Patricia Boya of the University of Fribourg, Switzerland, Tewin Tencomnao of Chulalongkorn University in Bangkok, and Evandro Fei Fang of the University of Oslo in Norway, the authors report that α-amyrin works its magic by stimulating mitophagy, boosting mitochondrial health and clearance of aggregated proteins. In a parallel, the scientists found that people who consumed high amounts of fruits and vegetables not only had a lower risk of dementia, but a hint of less p-tau217 in their blood. That it readily crosses the blood-brain barrier makes α-amyrin a therapeutic candidate, the authors contend.
Because α-amyrin survives for hours in the plasma and can cross the blood-brain barrier in mice, the authors are planning to test it in people. Fang told Alzforum that since pure α-amyrin is expensive, his group is working with industry partners to synthesize it. He did not know how many passion fruits a person would need to eat to benefit, but noted that his lab has detected α-amyrin in the skin and seeds, as opposed to the flesh. This distribution has been reported for other fruits, such as apples and tomatoes, as well (Brendolise et al., 2011; Bauer et al., 2004). Catalogued information about its concentration is not available, Fang told Alzforum. For now, he recommends that people simply add more colorful fruits and vegetables to their daily diet.
Read the full story: https://www.alzforum.org/news/research-news/fruity-finding-does-amyrin-boost-autophagy-thwart-tau-pathology
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