Alzheimer's Disease

This is a thread for all things related to Alzheimer’s Disease

Dysregulation of brain iron metabolism and iron accumulation is known to be associated with ageing and AD, although underlying mechanisms remain unclear. It is known that iron load and inflammation regulate the synthesis of hepcidin, the main iron regulatory protein. In particular, the inflammation-modulating cytokine interleukin-6 (IL-6), also known to modulate brain-muscle crosstalk, is involved in the activation of hepcidin synthesis in the brain. Although regular physical exercise is known to have a beneficial effect on total body iron metabolism and anti-inflammatory action, the role of regular exercise on iron homeostasis in the brain and in the context of AD remains unclear.

The researchers utilised wildtype mice and 5xFAD transgenic mice, modelling AD to explore the effect of regular physical exercise on the modulation of iron homeostasis. Half of the mice had unlimited use of a running wheel during the six-month experiment. The levels of iron and iron-related proteins were analysed in the brain and skeletal muscle. The researchers also investigated the potential involvement of iron in the crosstalk between the brain and periphery upon regular exercise.

The current study demonstrates that regular physical exercise modulates iron storage and trafficking in both the brain and skeletal muscle. Moreover, this study is the first to report a reduction of cortical hepcidin in response to regular physical exercise. The results suggest that IL-6 is a key modulator of hepcidin in exercise-induced brain iron modulation. These findings help to better understand why regular exercise is beneficial in AD, and may provide new insight for disease prevention or effective treatment approaches.

The study was conducted in the Neurobiology of Disease laboratory led by Associate Professor Katja Kanninen at the University of Eastern Finland. The study was supported by the Academy of Finland, the Sigrid Juselius foundation, the Finnish Cultural Foundation, and the University of Eastern Finland.

Source: University of Eastern Finland

tl;dr: exercise is good for your health.

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I wonder if there’s any study with psychodelics and alzheimer’s

Indeed, there are…

Very interesting. Psychedelics is commonly considered to have a rewiring effect. Given there’s a degradation of memory for Alzheimer’s, I wonder if this rewiring is a plus or minus…

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It was just a quick google search…I didn’t read much of it and certainly don’t claim to understand any of it…also, I just wanted to figure out how to spell “psychedelics” :wink:.

**** Alzheimer’s!!! :rage: :face_with_symbols_over_mouth:



My MIL has it and when my FIL spent a month in the hospital this winter my wife had to provide almost 24/7 care. It was horrible. We found a facility for her that’s pretty good, but it’s awful seeing what she has become.

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Scientists find medications that reverse Alzheimer’s disease

Researchers have managed to reverse the symptoms of Alzheimer’s disease in mice by administering drugs currently used to treat hypertension and inflammation in humans.

Alzheimer’s disease is the most common cause of dementia in Western societies and it is estimated that 24 million people worldwide have this condition.

ICREA researcher Dr Patrick Aloy , head of the Structural Bioinformatics and Network Biology lab at IRB Barcelona, has headed a study that has managed to reverse the symptoms of Alzheimer’s disease in mice by administering drugs currently used to treat hypertension and inflammation in humans.

In this study, the scientists led by Dr Aloy have characterised three stages of Alzheimer’s disease, namely initial, intermediate and advanced. For each of these stages, they have analysed the behaviour of the animals, studied the effects on the brain (specifically the hippocampus at the tissue level) and performed a molecular analysis to measure gene expression and protein levels.

The approach adopted has allowed them to describe the development of the disease at a level of detail hitherto unknown and also compare it with healthy ageing. “What we have observed is that, although Alzheimer’s disease shares some features of accelerated ageing, it is also affected by totally different ageing processes,” says Dr Aloy. “This disease is caused by the abnormal accumulation of certain proteins, and we have seen that, in some cases, this is not caused by overproduction but by an error in their removal,” he adds.

Having characterised the disease, the scientists used the Chemical Checker, a computational tool developed by the same research group to find drugs already on the market with the capacity to reverse the effects at the cellular level.

This tool has allowed them to identify a series of possible candidates, which were tested in various mouse models of Alzheimer’s disease. Four drugs – two non-steroidal anti-inflammatories and two anti-hypertensives, proved effective at reversing the disease and neutralising symptoms in these mice.

“Epidemiological studies already indicated that people who regularly take antiinflammatories show a lower incidence of Alzheimer’s disease, but this had not been correlated with a specific medication or mechanism. The results that we are publishing are most promising, and we hope that further research can be done on them because they could give rise to a paradigm shift in the treatment of this disease,” says Dr Aloy.

In addition to paving new avenues of research for the treatment of Alzheimer’s disease, the characterisation of the distinct stages of this condition published in this study favours early diagnosis.

Diagnosing Alzheimer’s disease at an early stage, when damage to the brain is still minimal, is one of the main research focuses to tackle this condition and to reduce symptoms.

This work has been done in collaboration with the RIKEN Center for Brain Science and the Institute of Brain Science, both in Japan, and the Biostatistics/Bioinformatics and also Proteomics core facility at IRB Barcelona. The study was funded by the European Research Council, the Spanish Ministry of Science and Innovation and the Government of Catalonia.

Source: ANI

tl;dr: “Four drugs – two non-steroidal anti-inflammatories and two anti-hypertensives, proved effective at reversing the disease and neutralising symptoms in these mice.” The effectiveness in humans is tbd.

There are other causes of dementia that can develop over time that aren’t Alzheimer’s. They suck, too.


From the Brain Health Registry…

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Exciting Updates in the Alzheimer’s Field!

During this year’s annual Alzheimer’s Association International Conference (AAIC), thousands of researchers gathered in San Diego, CA to present cutting-edge research on Alzheimer’s disease and related dementias. Several Brain Health Registry (BHR) researchers were among those presenting!

Brain Health Registry AAIC Highlights

During the conference, BHR Principal Investigator Dr. Mike Weiner described the enrollment of over 100,000 participants and study partners into the BHR. Furthermore, thousands of these individuals have been referred to additional research studies at other institutions to help facilitate important research.

Dr. Weiner also discussed BHR’s future directions and areas for improvement. A crucial objective is to enroll more participants of diverse racial, educational, and economic backgrounds to make the BHR more representative of the general population. This can help ensure that our research findings apply to everyone.

BHR Co-Investigator, Dr. Rachel Nosheny, facilitated presentations on ways in which data collected from a participant’s study partner (for example, a spouse or child) can provide valuable information about the participant’s memory and thinking.

Study partner insights may help researchers more efficiently identify individuals with impaired thinking and memory early on.

Dr. Miriam Ashford, a research scientist with BHR, shared research exploring participant experiences of BHR, such as whether the study site is easy to use, and how demographic characteristics like race and years of education shape these experiences.

Finally, Dr. Kristen Knight, a postdoctoral fellow with BHR, presented on how online data collected in BHR can be linked to whether a participant has increased amyloid in their brain — a hallmark of Alzheimer’s disease. This could help improve screening tools for identifying Alzheimer’s remotely, rather than in a clinical setting.

Advancements in the Field: AAIC Takeaways

Other AAIC presentations spanned a broad range of subjects, from understanding the complex biology of Alzheimer’s disease to strategies for supporting caregivers of individuals with dementia. Here are a few of the many important topics discussed: ​

Drug discovery and clinical trials

Many Alzheimer’s drugs, including the recently FDA-approved Aduhelm, target sticky plaques of amyloid protein in the brain. These drugs aim to slow the progression of Alzheimer’s disease.

However, due to mixed results from amyloid drug trials, researchers are continually seeking other strategies for drug development. These include targeting inflammation or swelling in the brain, tangles of another protein called tau, and even insulin resistance.

◊ Social determinants of health and diversity in Alzheimer’s research ​

Key findings discussed at AAIC reinforced the critical role factors like economic background, race, ethnicity, and educational attainment play in shaping a person’s brain health and Alzheimer’s disease risk.

For example, a study of approximately 1,000 middle-aged adults found that experiencing interpersonal and institutional racism was associated with lower scores on memory assessments.

Several presenters enumerated strategies for recruiting and retaining underrepresented groups of participants in research studies, including community-engaged research methods.

◊ Lifestyle factors

It’s well-established that lifestyle factors like exercise and diet are integral to maintaining both physical and brain health.

Recent findings from a multi-year study of over 300 participants with mild cognitive impairment suggests that regular exercise, either aerobic or not, may help slow the progression of cognitive decline.

I wonder if dementia is like tripping

oo great news.

We just need to slow it down enough that we’ll die before it kills us

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From the Brain Health Registry…

Promising Results from Alzheimer’s Drug Trial

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Promising Results from Alzheimer’s Drug Trial

Last month, pharmaceutical companies Eisai and Biogen announced positive results from a phase 3 clinical trial of an Alzheimer’s drug called lecanemab.

The trial spanned an 18-month period and enrolled about 1,800 participants with mild cognitive impairment or early-stage Alzheimer’s disease.

Compared to those who did not receive the drug, trial participants who received lecanemab experienced a 27% slower rate of cognitive decline.

“The Eisai announcement is good news for the Alzheimer’s field,” said Dr. Michael Weiner, the Principal Investigator of the Brain Health Registry. “Although these findings are significant, it’s important to note that the drug does not stop the progression of decline or restore function to those with impairment.”

Lecanemab was also associated with side effects, including swelling and bleeding in the brain. Most side effects were detected by MRI and caused no symptoms. There was a relatively low incidence of serious side effects.

Lecanemab is a type of antibody that targets clumps of amyloid protein in the brain. These amyloid plaques damage brain cells, contributing to memory and thinking issues in Alzheimer’s and related forms of dementia.

Findings from the lecanemab study support the “Amyloid Hypothesis” of Alzheimer’s, which proposes that the disease is linked to the buildup of amyloid protein in the brain.

Other treatments aimed at amyloid are currently being investigated. Alzheimer’s researchers also continue to seek drug targets other than amyloid, including another protein in the brain called tau.

Lecanemab is a “disease-modifying” therapy, meaning it targets the underlying biology of Alzheimer’s disease, rather than just easing symptoms. This distinguishes it from most other drugs on the market, aside from Biogen’s drug Aduhelm. Despite controversies around the results of two clinical trials, the FDA approved Aduhelm in June 2021. However, the Center for Medicare Services (CMS) did not approve Aduhelm for reimbursement. At present, Biogen is not actively marketing Aduhelm.

Eisai recently filed for accelerated FDA approval for lecanemab. This means that the drug could be approved as soon as early 2023. Eisai will also very likely request that CMS provide reimbursement. Most experts believe that, if approved, lecanemab may become available to the public in 2023 or 2024.

Results from the lecanemab trial will be presented during the annual Clinical Trials on Alzheimer’s Disease conference in November 2022. This will give researchers and the public a clearer understanding of the drug’s potential.

Measuring Cognitive Decline

The Eisai trial used a tool called the Clinical Dementia Rating (CDR) to assess lecanemab’s effectiveness at slowing cognitive decline.

The CDR is a commonly used scale that measures the severity of dementia symptoms.

The difference in CDR scores between participants who received lecanemab versus those who did not was 0.45 points, a minor, but significant difference.

Brain Health Registry researchers are currently working on developing on online version of the CDR, as part of our Electronic Validation Study.

Findings from this project could help researchers identify Alzheimer’s risk sooner and more efficiently. Because this version of the CDR could be administered online rather than in a clinic by a trained assessor, it could make research studies more accessible and scalable.

To read more about the Electronic Validation Study, click here.

tl;dr: The drug Lecanemab slowed down Alzheimer’s by 27%.

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From the Brain Health Registry…

New Insights from Alzheimer’s Drug Studies

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New Insights from Alzheimer’s Drug Studies

During this year’s Clinical Trials on Alzheimer’s Disease (CTAD) Conference, held from November 29th – December 2nd, about two thousand investigators from all over the world convened to present cutting edge research.

In this month’s newsletter, we summarize key findings from two of the clinical trials discussed during the conference.

What is Lecanemab?

Lecanemab, developed by pharmaceutical companies Eisai and Biogen, is a type of antibody that targets sticky clumps of amyloid protein in the brain. These amyloid plaques are a hallmark of Alzheimer’s disease; they are associated with the spread of another protein in the brain called tau, and thereby contribute to memory and thinking issues.

Lecanemab is a disease-modifying therapy, meaning it targets the underlying biology of Alzheimer’s to slow the disease’s progression. Such therapies aim to prolong milder stages of impairment, to preserve those with Alzheimers’ independence and quality of life for longer. The current treatments are not expected to cure or reverse the disease.

Initial results from a phase 3 clinical trial of lecanemab, released in September 2022, sent ripples of excitement throughout the scientific community. We summarized these findings in our October 2022 newsletter.

More recently, detailed results from the lecanemab trial were published in the New England Journal of Medicine, and unveiled to a crowd of hundreds during CTAD.

More Details on Lecanemab

Clinical trial participants who received lecanemabexperienced a 27% slower rate of cognitive decline than those who did not receive the drug. Those who took lecanemab performed better on assessments of memory and thinking and activities of daily living (for example, eating, grooming, and bathing) compared with those who did not.

Lecanemab not only cleared amyloid protein from the brain; the drug also reduced other biological markers of Alzheimer’s disease, including tau protein and brain inflammation.

Furthermore, the trial was done in a group of participants who better represented the United States population (though still under-included some groups), making the findings more likely to apply to everyone. 22.5% of participants identified Latino/Hispanic, and 4.5% identified as Black. Furthermore, the study enrolled many participants with other common conditions like obesity, diabetes, and heart disease.

About one out of every eight participants in the drug trial experienced swelling of the brain detected by brain scan. However, participants largely did not experience symptoms from this. Brain swelling has occurred as a side effect of other amyloid drugs, including the controversial, FDA-approved Alzheimer’s drug, Aduhelm.

Experts anticipate lecanemab will receive accelerated FDA approval in 2023. It is unclear to what extent Medicare and other insurers will pay for this treatment. Clinicians will need to determine how and when lecanemab can be prescribed to most benefit those living with Alzheimer’s disease and their families.


Amidst the excitement surrounding lecanemab, the outlook for another Alzheimer’s drug, gantenerumab, was not so sunny.

Developed by Roche, gantenerumab is also an anti-amyloid drug. During CTAD, researchers at shared details about two phase 3 clinical trials of this drug.

About 2,000 participants aged 50-90 participated in the trials, which spanned over two years. Participants who received gantenerumab had an 8% and 6% slowing in cognitive decline compared to participants who received placebo in the two trials. Neither of these differences were statistically significant, meaning the drug was not effective. Furthermore, the treatment did not lower amyloid plaques as much as was anticipated. This failure to eliminate plaques may be an explanation for the lack of clinical effect.

Although the gantenerumab findings were disappointing, the results from the trial still contribute to scientific understanding of Alzheimer’s disease.

Gantenerumab, alongside lecanemab and recent findings on another drug called donanemab (mentioned in our January 2022 newsletter), paint a clearer picture of the exciting potential, as well as some limitations, of anti-amyloid drugs.

Blood Tests for Alzheimer’s

Researchers at CTAD also showed more data indicating that blood tests are pretty good predictors of the presence of amyloid plaques. The blood tests are increasingly being used in clinical trials. Some companies (C2N Diagnostics and Quest) are now making some of these blood tests available for clinical use.

The drug Lecanemab slowed down Alzheimer’s by 27%.
The drug Gantenerumab did not have a statistically significant effect.

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From the Brain Health Registry…

Ties Between Alzheimer’s Disease and Diabetes

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Ties Between Alzheimer’s Disease and Diabetes

There are over 34 million people in the United States living with diabetes, and over 6 million with Alzheimer’s disease. As both these conditions increase in prevalence, it’s important to understand the ways in which they may be connected.

Understanding Diabetes

According to the Alzheimer’s Association, around 54 million adults in the United States have prediabetes, or blood sugar levels that are higher than average. Many of these adults will develop Type 2 diabetes within a decade.

Type 2 diabetes, which accounts for 90 – 95% of diabetes cases, usually develops over time, and often begins with insulin resistance. When a person’s blood sugar increases, the pancreas receives a signal to release insulin. Insulin is a hormone that helps blood sugar (also known as glucose) enter cells in the muscles, liver, and fat, providing energy for the body.

In diabetes, these cells cannot use insulin effectively. To compensate, the body requires increasingly large amounts of insulin to allow glucose into cells. Eventually, the pancreas is unable to meet demands and produce enough insulin, and glucose lingers in the bloodstream.

Over time, this excess glucose can damage various parts of the body, including the kidneys, eyes, and nerves.

The Impact of Diabetes on the Brain

High blood sugar can gradually damage the blood vessels in the brain. If the brain does not receive enough blood, brain cells can die, impacting a person’s memory and thinking.

Diabetes also increases a person’s risk for stroke and heart disease, which can both heighten Alzheimer’s risk.

Elevated blood sugar may also cause inflammation in the brain, harming brain cells, and possibly contributing to Alzheimer’s disease.

In a Harvard University study of over 10,000 adults in the UK, researchers examined the association between dementia onset and the age at which participants developed diabetes. Participants were monitored from 1985 until 2019. The researchers found that a person’s risk for developing dementia increased the younger they developed diabetes.

A Closer Connection

A key player in diabetes, insulin may also play a role in the formation of sticky plaques of beta-amyloid protein in the brain. Amyloid is an established hallmark of Alzheimer’s disease. Similarly, processes in diabetes may contribute to toxic clumping of tau protein in the brain, another key marker of Alzheimer’s disease.

Other research suggests that certain genetic factors and diabetes may work together to increase Alzheimer’s risk.

Some researchers are even testing the controversial hypothesis that Alzheimer’s is an additional type of diabetes — “type 3 diabetes” — but there is not clear-cut evidence to support this.

The relationship between Alzheimer’s disease and diabetes is complex, but research into this topic is continually evolving.