Alzheimer’s risk linked to compound found in popular joint health supplements

 Contact your doctor for validation; s/he won't know a damn thing, but it will just prove how incompetent they are in not being up-to-date on research!

Alzheimer’s risk linked to compound found in popular joint health supplements

Many older adults turn to glucosamine to manage aging joints, but for individuals with mild cognitive impairment, the supplement could be linked to faster progression to Alzheimer’s disease.

To investigate how glucosamine affects dementia risk and mortality, University of Florida researchers analyzed medical records of patients with mild cognitive impairment, tracked laboratory mouse models and examined healthy versus Alzheimer’s-affected human brains.

The study, which was published in Nature Metabolism, focused on glycosylation, a natural process where brain cells attach small chains of sugar to proteins.

"You can think of these sugar chains as the labels and fittings on a machine part — they help a protein fold correctly, get shipped to the right place in the cell and connect with its partners," senior author Ramon Sun, Ph.D., professor of biochemistry and molecular biology in the College of Medicine at University of Florida, told Fox News Digital. "The right amount is essential."

 "Glucosamine is a naturally occurring compound of sugar and an amino acid group that is a fundamental structural building block in the body," Neil Levin, senior nutrition education manager of Now, a manufacturer of glucosamine supplements in Illinois, told Fox News Digital.

Glucosamine is concentrated in cartilage, the connective tissue that cushions joints, and is a component of larger molecules that help give cartilage its strength, elasticity and ability to retain water, he added.

"Support for aging joints is the primary reason people take glucosamine as a dietary supplement," Levin said.

The body uses an internal "checkpoint" that naturally regulates how many of these sugar chains it produces, according to Sun.

Supplemental glucosamine bypasses that "front gate" entirely — like a delivery truck pulling straight up to the loading dock, instantly boosting the supply of raw material used to make the sugar chains, the expert added.

In the study, researchers analyzed thousands of patients with dementia, including Alzheimer's disease, as well as those with mild cognitive impairment, and then narrowed the group to those who were taking glucosamine.

For those with mild cognitive impairment, taking the supplement didn't change their risk of death, but it did make them 25% more likely to progress to dementia. However, among individuals who already had dementia, glucosamine users had a higher mortality compared to similar non-users.

The researchers also examined brain tissue to understand what might be driving the association. "We found an excess of sugar chains on proteins in the Alzheimer’s brain," Sun said.

Many of those proteins help nerve cells communicate, but the excess sugar chains may interfere with how they function, Sun said. He compared the effect to coating a key in too much wax — it is still the same key, but no longer fits the lock properly.

Glucosamine is one of the materials cells use to make these sugar chains, according to Sun.

Researchers also tracked how glucosamine was processed in mice, comparing its effects on healthy brains with those affected by Alzheimer’s-like disease.

"In our experiments, normal mice given glucosamine showed no increase in these sugar chains and no change in a memory test," Sun said.

"But in mice with Alzheimer's-like disease, where the production line was already running too hot, glucosamine increased the sugar chains further and worsened performance on a memory test."

The researchers relied on medical records, which may not capture every supplement a patient was taking.

"Health records tell us what was documented, not everything a person took," Sun said. "Over-the-counter supplements are not always recorded, and records don't reliably capture dose, brand or how consistently someone took it."

Glucosamine users may also differ in factors such as arthritis, pain, mobility, frailty and medication use, Levin noted. The records also did not establish the exact supplement, dose, duration or consistency of use.

"The finding should therefore be treated as a safety signal that warrants controlled human research, but it did not — could not — reach a conclusion that glucosamine causes Alzheimer’s disease," Levin said.

The next step is a well-designed, double-blind clinical trial to evaluate the impact of glucosamine on cognitive decline in patients with dementia.

[Alzheimer’s] disease, which is why doing this research properly, including the clinical trial we've called for, matters," Sun said.

The study did not examine cognitively healthy people and does not suggest that glucosamine poses a risk to those who take it for joint health.

"A brain affected by dementia and a healthy brain are different biological environments, and we shouldn't assume a supplement behaves the same way in both," Sun said.

He emphasized the importance of consulting with a doctor before starting or stopping a supplement.

"If you or a family member has a diagnosis of cognitive impairment or dementia and takes glucosamine, it's reasonable to bring it up at the next visit, as part of an ordinary conversation about what's in the medicine cabinet," the doctor advised.

Fox News Digital reached out to multiple glucosamine manufacturers requesting comment.

Original article source: Alzheimer’s risk linked to compound found in popular joint health supplements

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MRI Study Links Tightness of High-Convexity Sulci to Higher Risk of Cognitive Decline in Older Adults

Will your competent? doctor and hospital  GUARANTEE THAT FOLLOWUP RESEARCH WILL OCCUR THAT STOPS THIS PROBLEM!

Can't do that? PURE INCOMPETENCE AND A FIREABLE OFFENSE!

MRI Study Links Tightness of High-Convexity Sulci to Higher Risk of Cognitive Decline in Older Adults

Tightness of the high-convexity sulci (THC) on brain MRI was associated with nearly threefold higher odds of cognitive decline over five to seven years of follow-up, according to a new prospective study involving over 2,100 community-dwelling senior citizens.

Emerging brain MRI research suggests that tightness of the high-convexity sulci (THC) is associated with significantly elevated risks for long-term cognitive decline.

For the prospective study, recently published in Radiology, researchers reviewed brain MRI scans and cognitive assessments for 2,133 community-based participants (median age of 69) with a five to seven-year follow-up period. For the baseline MRI scans, the study authors assessed participants for key features of disproportionately enlarged subarachnoid space hydrocephalus (DESH), including THC, an Evans index > 0.3 and enlargement of the Sylvian fissures (ESF).

The researchers found that 46.3 percent of the cohort had incomplete DESH (defined as one or two of the aforementioned DESH features) and only 1.7 percent of the cohort had complete DESH (all three of the aforementioned features). There were no DESH features on baseline MRI for 51.9 percent of the cohort, according to the study authors.

Here one can see brain MRI scans revealing ventricular enlargement and different features of disproportionately enlarged subarachnoid space hydrocephalus (DESH), including an Evans index > 0.3 (A), a focally enlarged sulci (B), temporal horn enlargement (> 6 mm) (C), a reduced callosal angle (< 90^o) (D) and periventricular hyperintensity with correspondence to Fazekas grade 3 (E). (Images courtesy of Radiology.)

However, the presence of THC on baseline MRI was associated with a nearly threefold higher risk for cognitive decline within five to seven years. The researchers noted the elevated risk was evident in the entire cohort as well as those deemed to be cognitively normal in baseline testing.

“These findings suggest that careful assessment of THC may aid early risk stratification. Future studies incorporating longitudinal imaging will be needed to clarify the mechanisms underlying THC and to establish its role in early risk stratification for cognitive decline,” noted lead study author Kana Saito, MD, who is affiliated with the Department of Radiology at the Hirosaki University Graduate School of Medicine in Hirosaki, Japan, and colleagues.

Three Key Takeaways

• Tightness of the high-convexity sulci (THC) on brain MRI may be a useful early warning sign. In this prospective study of 2,133 community-dwelling older adults (median age 69), THC at baseline was linked to a nearly threefold higher risk of cognitive decline over five to seven years. The association held in participants who were cognitively normal at baseline, which suggests the finding could help with risk stratification before symptoms appear.

• THC combined with Sylvian fissure enlargement may be more informative than traditional DESH criteria. People who had both THC and enlarged Sylvian fissures (ESF) were 83 percent more likely to have long-term cognitive decline. The authors suggest this pairing may be a more clinically meaningful marker than the Evans index or complete DESH. Complete DESH was rare in the cohort (1.7 percent), while incomplete DESH was common (46.3 percent). This supports assessing individual DESH features rather than only the full triad.

• The findings are promising but not yet ready for routine use. Cognitive outcomes were based on clinical diagnosis of MCI or dementia rather than standardized neuropsychological testing. The cohort was also limited to older Japanese adults from a single region, which may restrict generalizability. The authors call for longitudinal imaging studies to clarify how THC develops and to confirm its role in early risk stratification.

Scientists thought this peptide was harmless. A new discovery could rewrite Alzheimer’s research

 With your risk of dementia post stoke, you'll need your competent? doctor and hospital to GUARANTEE THAT FOLLOWUP RESEARCH WILL OCCUR THAT STOPS THIS PROBLEM!

Can't do that? PURE INCOMPETENCE AND A FIREABLE OFFENSE!

Scientists thought this peptide was harmless. A new discovery could rewrite Alzheimer’s research

Lab research suggests the little-studied peptide can form amyloid clumps and may damage neurons, but its role in Alzheimer’s patients remains unproven.

For decades, the search for an Alzheimer’s treatment has centered on one major culprit—amyloid beta. But now, a University of California Santa Cruz chemist argues that scientists may have overlooked a closely related peptide long dismissed as harmless in their research.

In a commentary published in the peer-reviewed journal ChemBioChem, Jevgenij Raskatov, PhD, professor of chemistry and biochemistry at UC Santa Cruz, highlights new research which suggests that the lesser-known peptide, P3, can form the same clumps and fibrils as amyloid beta, the target of most Alzheimer’s drug development. P3 may also interact with amyloid beta, influencing how it builds up and how toxic it becomes.

These findings ultimately suggest that P3 may be contributing to the nerve cell damage associated with Alzheimer’s disease. 

“The P3 peptide is, most likely, not the innocent bystander it was commonly thought to be. There’s still more research to be done. But this could turn Alzheimer’s research on its head,” Raskatov said in a release. Instead, he’s proposed to rename it amyloid alpha, or Aα.

What P3 is and why scientists dismissed it

Amyloid beta comes from a large protein embedded in cell membranes called the Amyloid Precursor Protein (APP). Two enzymes, β-secretase and γ-secretase, cut the protein in a sequence, freeing amyloid beta fragments of different lengths.

Previously, researchers have focused on two of those fragments, Aβ40 and Aβ42. Aβ42 has been reviewed the most because it is especially prone to sticking together and clumping into toxic aggregates. 

 Related video: Study identifies protein that could help protect memory as we age (WKYC-TV-Cleveland) 

But unlike amyloid beta, P3 forms when APP is processed through a different sequence of molecular cuts. The enzyme α-secretase acts first, and then γ-secretase, and P3 forms when alpha-secretase does. Researchers previously assumed that P3 stayed dissolved and didn’t clump, nor was it presumed to be toxic. But Raskatov did not believe that these assumptions were ever adequately tested.

“We were looking at the peptide sequence and noticed that two-thirds of charged residues were located in the N-terminal segment of A-beta that was missing in A-alpha,” Raskatov told Inc. Since charged residues help a molecule dissolve in water, P3’s lack of them casts doubt on the idea that it simply stays in solution, he said.

The evidence that P3 may not be harmless

Over the past five years, Raskatov’s team published three studies showing that P3 forms amyloid aggregates faster than amyloid beta and may be toxic to neurons, though less so. An independent group in the United Kingdom has since confirmed the findings, according to the release. Though, it is important to note that this new paper is a commentary, not a study. The research it draws on was done in the lab, and whether P3 contributes to Alzheimer’s in patients still remains unproven.

Raskatov told Inc. that it is impossible to know exactly what the narrow focus on amyloid beta has cost the field, but it has likely been damaging. 

“Focusing on a subset of the problem instead of the whole picture is likely to be limiting in ways that are hard to predict,” Raskatov told Inc. “How can you rationally solve a problem that you don’t understand?”

What P3 could mean for Alzheimer’s treatments

Targeting multiple amyloid species might change treatment strategy, he said, especially given how common P3 may be. Raskatov noted that alpha-secretase processing appears roughly twice as prevalent in neurons as beta-secretase processing. 

“This means that A-alpha is likely the main product of APP processing and not A-beta,” Raskatov said, adding that “only more experiments can determine what exactly that means.”

This post originally appeared at inc.com.

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Neurophysiological assessment of stroke recovery after repetitive transcranial magnetic stimulation

 

'Assessments' have NEVER gotten anyone recovered! More useless crapola from your completely fucking incompetent stroke medical world! You're all fired!

Here, send me hate mail at oc1dean@gmail.com explaining EXACTLY how this gets survivors recovered! If you can't stand behind your name and title; RUN AWAY with your tail between your legs!

Neurophysiological assessment of stroke recovery after repetitive transcranial magnetic stimulation

Devisree Dhanachezhiyan [1]

,

Subasree Ramakrishnan [2]

,

Deepak Menon [2]

,

Anupam Gupta [3]

,

Selva Ganapathy [3]

,

Talakad Narsappa Sathyaprabha [1]

,

Kaviraja Udupa* [1]

Author Affiliations

1Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India

2Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India

3Department of Neurorehabilitation, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India

*Correspondence: kaviraja.e03234@nimhans.net

Abstract

Stroke is a major cerebrovascular disorder that commonly causes motor and cognitive impairments, significantly affecting the quality of life of stroke survivors. Upper-limb dysfunction is one of the most frequent complications after stroke, affecting nearly 77% of patients and limiting their ability to perform daily activities independently. In recent years, repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, has gained increasing attention as a potential therapeutic approach for improving upper-limb motor recovery after stroke. This narrative review aims to discuss the neurophysiological basis of rTMS-induced motor recovery and examine the role of neurophysiological biomarkers in evaluating treatment outcomes. Relevant literature was identified through searches of electronic databases, including PubMed, Scopus, and Google Scholar, focusing on studies related to rTMS, cortical excitability, electroencephalography (EEG), heart rate variability (HRV), and post-stroke motor recovery. Current evidence suggests that rTMS may promote(Stop using weasel words!) recovery by modulating cortical excitability, restoring interhemispheric balance, and influencing functional connectivity and autonomic regulation. Neurophysiological measures such as TMS-derived cortical excitability parameters, EEG activity, and HRV indices may help understand the mechanisms underlying recovery and the therapeutic effects of rTMS. However, studies integrating these neurophysiological measures remain limited. This review highlights the importance of combining neurophysiological assessments with rTMS to better understand post-stroke recovery mechanisms and support the development of more targeted rehabilitation strategies.

Genetic Evidence Points to Brain’s Triple Network as a Driver of Stroke Recovery

 Will your incompetent? doctor and hospital DO NOTHING  to get this followed up into an EXACT STROKE REHAB PROTOCOL?  The answer tells you about incompetence!

Genetic Evidence Points to Brain’s Triple Network as a Driver of Stroke Recovery

Every year, millions of people survive an ischemic stroke only to face a long and uncertain road of rehabilitation. Some recover their speech, movement, and memory with remarkable speed; others plateau despite months of therapy. For decades, neuroscientists have known that the brain’s intrinsic functional networks—the large-scale circuits that hum with coordinated activity even when we are at rest—correlate with how well patients recover. But correlation is not causation, and this distinction has long frustrated the field. Now, a study published in Experimental  Biology and Medicine offers some of the strongest  genetic evidence yet that specific brain networks may actively drive recovery after a mild, nondisabling ischemic stroke, and that cholesterol may shape cognitive outcomes partly through these very circuits.

The research team, led by investigators from hospitals in Guangdong and Zhejiang, China, turned to a technique called Mendelian randomization, a statistical framework that exploits the random shuffle of genes at conception as a natural experiment. Because genetic variants are fixed at birth and cannot be altered by disease or environment, they can serve as proxies for exposures in ways that conventional observational studies cannot. If people who inherit variants associated with stronger functional connectivity in a given brain network also tend to recover better after stroke, the argument for a causal contribution becomes far more compelling than any correlational finding.

To build this genetic case, the researchers drew on a genome-wide association study of 34,691 UK Biobank participants, from which they extracted instruments for 191 resting-state functional magnetic resonance imaging phenotypes. These phenotypes, derived from spontaneous low-frequency fluctuations of the blood oxygen level–dependent, or BOLD, signal, capture two fundamental properties of brain organization: the amplitude of neural activity within individual nodes, and the temporal correlation between pairs of regions, known as pairwise functional connectivity. On the outcome side, they used genetic data from 1,270 patients with nondisabling ischemic stroke enrolled in the Vitamin Intervention for Stroke Prevention trial, whose motor, cognitive, and global impairments were tracked with National Institutes of  Health Stroke Scale subscales every three months over two years.

The headline finding centers on what neuroscientists call the triple network: the default mode network, the central executive network, and the salience network. The salience network, anchored in the anterior insula and dorsal anterior cingulate cortex, detects behaviorally relevant stimuli and orchestrates dynamic switching between the internally oriented default mode network and the externally oriented central executive network. The central executive network supports working memory, performance monitoring, and error correction, while the default mode network contributes to memory-based prediction and self-referential processing. The study found that people who inherited variants predicting stronger connectivity within this triple network—specifically between the default mode and central executive networks, and between the central executive and salience networks—showed significantly greater motor improvement after stroke, with an effect estimate of 0.399 and a p-value of 8.33 × 10⁻¹⁶, one of the most statistically robust associations in the entire analysis.

Remarkably, the same triple-network connectivity phenotype was also associated with better cognitive recovery, alongside two additional network features. Stronger connectivity between parietal and frontal regions, part of the frontoparietal network that underpins attention and working memory, predicted better cognitive outcomes. Resting frontal BOLD signal features linking the central executive network with the salience and default mode networks were likewise tied to greater cognitive improvement. Within the limbic network, higher genetically predicted BOLD fluctuation amplitude in the orbitofrontal region was associated with better motor recovery, hinting that emotional and motivational circuits may play an underappreciated role in physical rehabilitation. Notably, no network phenotype survived multiple-testing correction for global recovery, suggesting that the causal architecture of recovery is genuinely domain-specific rather than a single general-purpose property of the brain.

The technical rigor of the analysis deserves emphasis. The primary method was the multiplicative random-effects inverse-variance weighted approach, supplemented by weighted median, MR-Egger, constrained maximum likelihood, debiased inverse-variance weighted, and Bayesian weighted Mendelian randomization estimators, with MR-Pleiotropy Residual Sum and Outlier used to flag problematic variants. A causal relationship was declared only if all methods agreed in direction and the inverse-variance weighted p-value passed a stringent Bonferroni threshold of 8.73 × 10⁻⁵, correcting for 191 phenotypes and three outcomes. Sensitivity analyses found no evidence of heterogeneity among instruments, no single variant driving the results in leave-one-out plots, no statistical signal of horizontal pleiotropy, and no reverse causation when the analyses were run backward. The team even adjusted for collider bias—the distortion that can arise from conditioning on stroke survivors—using corrected weighted least squares based on GIGASTROKE consortium data, and the associations held firm.

Perhaps the most provocative result involves cholesterol. Low-density lipoprotein cholesterol is a well-established risk factor for ischemic stroke, but its role in recovery has been murky, partly because post-stroke lipid levels are heavily influenced by medication and clinical circumstances. Using  genetic instruments for lipid traits from a circulating metabolite genome-wide association study of 136,016 participants, the researchers found that genetically proxied higher LDL-C was associated with poorer cognitive recovery, while triglycerides and HDL-C showed no such link. Digging into LDL subfractions, they discovered that total cholesterol in large, medium, and small LDL particles was associated with the triple-network connectivity phenotype itself.

This set the stage for a two-step mediation analysis. The logic is elegant: if lipids influence the brain network, and the brain network influences recovery, then the network may sit on the causal pathway between cholesterol and cognitive outcome. The product-of-coefficients method, with standard errors from the delta method, suggested that triple-network connectivity partially mediates the association between LDL-C liability and cognitive recovery, accounting for roughly 14 to 15 percent of the total effect. The mediation estimates were modest in absolute terms—around −0.008 to −0.009—but their confidence intervals excluded zero, and Steiger directionality tests supported the inferred causal order. The authors propose plausible mechanisms, including neuroinflammation, endothelial dysfunction, altered cerebral perfusion, impaired neurovascular coupling, and even amyloidogenic pathways, all of which are known targets of atherogenic lipids.

Important caveats temper these findings. The BOLD signal reflects not only neural communication but also the vascular and metabolic systems that support it, so the imaging phenotypes may capture variation in neurovascular  health as much as in network organization—particularly relevant when the exposure is cholesterol, which directly affects blood vessels. The outcome cohort was predominantly of European ancestry and modest in size, the NIHSS subscales are relatively coarse measures of impairment, and the summary-level design could not account for lesion location, even though strokes situated within or adjacent to key networks would themselves alter measured connectivity. Moreover, the genetic instruments were derived from healthy UK Biobank participants, meaning the results reflect lifelong liability to network properties rather than the possibility that modifying connectivity after a stroke would improve recovery.

Even with these limitations, the study opens genuinely new territory. It provides hypothesis-generating evidence that the triple network is not merely a correlate of recovery but a potential causal scaffold—one that supports motor relearning through attention, error correction, and compensatory strategy selection, and cognitive rehabilitation through executive control and self-monitoring. It also raises the tantalizing question of whether lipid management could preserve intrinsic network function and protect cognitive recovery, a testable proposition for prospective clinical studies. And it points toward interventions such as noninvasive brain stimulation, which could in principle modulate the connectivity patterns identified here. For a field that has long relied on correlational imaging studies, the arrival of genetically informed causal evidence marks a meaningful step toward understanding why some brains recover better than others—and what might be done to help those that do not.

Subject of Research: Neuroscience

Article Title:  Genetic evidence for causal relationships between brain functional networks and domain-specific recovery after nondisabling ischemic stroke

Article References: Cai, H., Huang, Z., Liang, J., Zhang, H., & Liu, Z. (2026). Genetic evidence for causal relationships between brain functional networks and domain-specific recovery after nondisabling ischemic stroke. Experimental Biology and Medicine, 251, Article 10948. https://doi.org/10.3389/ebm.2026.10948

Image Credits: AI Generated

DOI: 10.3389/ebm.2026.10948