Brain Stimulation May Help Improve Alzheimer’s Symptoms: Study

Brain Stimulation May Help Improve Alzheimer’s Symptoms

Researchers at Charité – Universitätsmedizin Berlin have discovered a brain network that, when stimulated, can improve Alzheimer’s symptoms.

Deep brain stimulation (DBS) is a surgical procedure used to treat specific neurological diseases such as Parkinson’s disease, essential tremor, epilepsy, and dystonia. More than 160,000 individuals receive this therapy annually.

Several psychiatric conditions, such as drug addiction, obsessive-compulsive disorder (OCD), and treatment-resistant depression, have been the subject of prior studies that looked at DBS as a potential treatment.

Deep brain stimulation, administered by a pacemaker-like device, can also be one of the potential treatments for alleviating Alzheimer’s symptoms. A group of researchers at Charité – Universitätsmedizin Berlin has found that altering a particular network in the brains of Alzheimer’s patients can lessen their symptoms. The study, published in the journal Nature Communications, has provided hope for additional investigation in this area.

What is Deep Brain Stimulation (DBS)?

DBS is a surgical process in which doctors implant electrodes in a specific brain region of a person. These electrodes connect to wires that lead to an electric generator (similar to a cardiac pacemaker) inserted under a person’s collarbone.

The electrodes produce electric pulses that disrupt any aberrant signals the brain may receive that result in disease symptoms like tremors or movement difficulties.

DBS and Alzheimer’s

In a previous Canadian study about the use of DBS to treat obesity, the researchers discovered that DBS produced flashbacks to childhood memories in some study participants. They then investigated if stimulating this specific spot in the fornix portion of the brain could help treat Alzheimer’s. This observation became the basis of the current study.

The fornix houses the brain’s white matter. Previous studies have also linked fornix neurodegeneration to Alzheimer’s and looked into using DBS to stimulate that part of the brain to treat dementia.

The current study added to the body of knowledge by examining data from electrodes placed in the same area of the fornix in 46 persons with moderate Alzheimer’s disease.

Following an analysis, scientists reported no improvement in most patients’ symptoms. However, several people “benefited considerably” from the treatment. These participants had a specific brain circuit stimulated and showed cognitive benefits after treatment.

According to Dr. Horn, one of the authors, this retrospective study aims to determine the variations between participants in which the treatment performed better than others.

DBS therapy obstacles

What has prevented DBS from treating Alzheimer’s while the doctors are already employing it to treat neurological disorders like Parkinson’s? Dr. Jean-Philippe Langevin, a neurosurgeon and director of the Restorative Neurosurgery and Deep Brain Stimulation Program for Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, has pointed out two chief reasons for this.

First, surgery is a more invasive and risky process than other therapies. The second is that DBS comes with an implantable device that needs adjustments, and often medical professionals struggle to use the programming devices.

He further pointed out that manufacturers have recently improved the software and device programmers, making them more user-friendly and intuitive.

What will be the next phases in DBS research?

Although DBS technology is advancing, it might still be some time before Alzheimer’s patients can get this treatment.

Dr. Horn stated that The ADvance II trial is presently underway in various centers worldwide. According to his understanding, if successful, it would increase the likelihood that the technique will receive both an FDA approval and a CE mark. As a result, many individuals who meet the requirements for which researchers have found DBS to be beneficial may be able to receive therapy.

Nevertheless, Dr. Horn cautioned that DBS is not a cure for neurodegenerative illnesses such as Parkinson’s or Alzheimer’s. Unfortunately, the disease will worsen, and the treatment will be symptomatic, at best helping to alleviate some of the symptoms for a short period.

References

  • Wang, T.R., Moosa, S., Dallapiazza, R.F., Elias, W.J. and Lynch, W.J., 2018. Deep brain stimulation for the treatment of drug addiction. Neurosurgical focus, 45(2), p.E11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329833/.
  • Mar-Barrutia, L., Real, E., Segalás, C., Bertolín, S., Menchón, J.M. and Alonso, P., 2021. Deep brain stimulation for obsessive-compulsive disorder: A systematic review of worldwide experience after 20 years. World journal of psychiatry, 11(9), p.659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474989/.
  • Roet, M., Boonstra, J., Sahin, E., Mulders, A.E., Leentjens, A.F. and Jahanshahi, A., 2020. Deep brain stimulation for treatment-resistant depression: Towards a more personalized treatment approach. Journal of Clinical Medicine, 9(9), p.2729. https://pubmed.ncbi.nlm.nih.gov/32846987/.
  • Ríos, A.S., Oxenford, S., Neudorfer, C., Butenko, K., Li, N., Rajamani, N., Boutet, A., Elias, G.J., Germann, J., Loh, A. and Deeb, W., 2022. Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer’s disease. Nature Communications, 13(1), p.7707. https://www.nature.com/articles/s41467-022-34510-3

Two Significant Alzheimer’s Risk Factors Affect Men More Than Women

Two Significant Alzheimer’s Risk

Researchers from the University of Alberta have found that two crucial risk factors for Alzheimer’s disease have substantially different effects on men and women.

Women are diagnosed with Alzheimer’s disease at a higher rate than men. One explanation for this is that women live longer than men, but other neurological and hormonal changes in midlife also play a role.

However, a recent study has highlighted two key risk factors – a particular gene and vascular health – that affect men more than women. According to Roger Dixon, one of the co-authors, the discovery that these two risk variables do not have the same impact on women emphasizes the need to consider gender differences when diagnosing and treating Alzheimer’s.

What are the research findings

In the large-scale investigation, the researchers employed neuroinformatics to examine data from 623 older persons over 44 years of their lives, aged 53 to 97, taken from the Victoria Longitudinal Study database.

The researchers examined two known Alzheimer’s risk factors: the bridging integrator 1 (BIN1) gene and vascular health, determined by pulse pressure. They then studied episodic memory impairment, a known early sign, in men and women. Episodic memory is our recollection of everyday events, such as what we had for breakfast the day before.

The study exhibited the following findings:

  • Poor vascular health (high pulse pressure) negatively impacted memory deterioration for everyone.
  • Even good pulse pressure did not protect people with BIN1 genetic risk from memory loss.
  • Males with BIN1 genetic risk along with poor vascular health had much steeper slopes, indicating a significant deterioration in memory, whereas females did not.

Since Alzheimer’s has an “insidious onset”, according to Dixon, they looked at data worth 44 years. That means it begins long before we can detect it. There are brain changes that are early indicators of the disease, not just five years before diagnosis but 10, 15, and 20 years before diagnosis.

Dixon further explained that many studies are attempting to identify those who are most at risk for Alzheimer’s long before they develop it because once they do, there is nothing we can do except mitigate some of the symptoms.

Prevention Pathways

According to Dixon, the fact that everyone develops some risk factors as they get older and that various risk factors can result in Alzheimer’s is another complicating element. Therefore, no one risk factor will reveal to researchers whether a person will acquire it; instead, it is a combination that develops through time. However, they can track and pinpoint who is most vulnerable if they have the correct data.

Because numerous paths contribute to Alzheimer’s, the researchers looked at both genetic risk and vascular health separately and simultaneously.

Some pathways point in Alzheimer’s direction, while others point away from the disease. Dixon further stated that finding subtypes as determined by these risk variables is what they are attempting to achieve and that they are trying to find out which subtypes are most likely to benefit from which form of risk intervention or risk reduction intervention.

References

  1. Heal, M., McFall, G.P., Vergote, D., Jhamandas, J.H., Westaway, D. and Dixon, R.A., 2022. Bridging Integrator 1 (BIN1, rs6733839) and Sex Are Moderators of Vascular Health Predictions of Memory Aging Trajectories. Journal of Alzheimer’s Disease, (Preprint), pp.1-17. https://content.iospress.com/articles/journal-of-alzheimers-disease/jad220334.
  2. Key Alzheimer’s Risk Factors Affect Men More Than Women. Neurosecience. https://neurosciencenews.com/male-alzheimers-risk-22208/. Published online: 20th Jan, 2023. Accessed: 2nd Feb, 2023.
  3. Men more than women affected by key Alzheimer’s risk factors: U of A study. Edmonton Journal. https://edmontonjournal.com/news/local-news/men-more-than-women-affected-by-key-alzheimers-risk-factors-u-of-a-sudy. Published online: 29th January, 2023. Accessed: 2nd Feb, 2023.

New Blood Test Can Accurately Predict Alzheimer’s Years Before First Symptoms Appear

New Blood Test Can Accurately Predict Alzheimer’s

A new blood test can identify a hidden toxin that causes Alzheimer’s years before symptoms such as memory loss or confusion appear. It could considerably speed up the diagnosis if further tested and scaled up.

To detect the onset of Alzheimer’s years before any signs of cognitive impairment manifest, researchers have created a novel laboratory test that measures levels of a “toxic” protein. According to the research published in Proceedings of the National Academy of Sciences, the results could help identify people at risk for the disease and assist in developing early treatments for the condition.

What led to the development of the SOBA test?

The novel blood test, developed by researchers at the University of Washington (UW), detects a molecular precursor in the blood that can lead to the abnormal folding and clumping of proteins and the formation of amyloid beta (Aβ) plaques in the brain.

Although Aβ plaques are a well-known indicator of Alzheimer’s disease, it is unclear how they affect cognitive loss. Traditionally, scientists have considered these extracellular plaques as an early initiator of neuron malfunction and loss, which ultimately causes cognitive decline.

However, according to new research, only one-third of Alzheimer’s patients have these plaques, and occasionally, persons without cognitive impairments also have them in their brains. In other words, extracellular A plaques in the brain may not be essentially toxic by themselves, but they might derive from molecular toxins that are notoriously difficult to detect.

In essence, these toxins are the functional forms of the A present inside cells. Some researchers believe these “toxic A oligomers” can inadvertently damage neurons from afar, making them more susceptible to extracellular plaques and clumps.

Although the specifics are still unknown, the theory prompted UW researchers to develop the remarkably precise soluble oligomer binding assay or SOBA.

SOBA employs a unique synthetic test surface that can bind to proteins in the blood, allowing it to detect the presence of toxic oligomers.

SOBA can predict who currently has Alzheimer’s and who might get it later

Researchers discovered that the soluble oligomer binding assay, or SOBA, could find oligomers in the blood of Alzheimer’s patients. About eleven participants had oligomers in the control group, which only consisted of individuals who displayed no symptoms of cognitive impairment at the time of taking blood samples.

Ten of those individuals were able to receive medical attention, and all of them later received a diagnosis of moderate cognitive impairment (MCI) or brain pathology associated with Alzheimer’s. Before any symptoms appeared, the test had already identified those at risk, and the toxic oligomers were missing from the blood samples of those who never went on to have cognitive impairment.

In another assessment of the test, researchers collected blood samples from 310 research participants who had previously provided blood samples and some of their medical information for Alzheimer’s research. The subjects did not exhibit any symptoms of dementia, Alzheimer’s, moderate cognitive impairment, or any other type of cognitive impairment at the time the blood samples were obtained.

SOBA discovered oligomers in the blood of people with MCI and moderate to severe Alzheimer’s. Researchers examined the brains of 53 participants via autopsy after they died and found toxic oligomers in the blood samples of 52 of those cases. The blood samples were taken years before their deaths.

Researchers hope to make tests widely accessible and affordable.

To transform SOBA into an oligomer diagnostic test, the research team is collaborating with researchers at AltPep, a UW spinout firm.

Dr. Daggett, one of the researchers, has stated that they desire a method that can identify Alzheimer’s in the best-case scenario without requiring lumbar punctures or costly imaging procedures. Besides, the test appears to be much more sensitive and specific than other testing methods.

Instead of requiring costly technology and processing, she claimed that SOBA only needs a standard, straightforward blood test that is inexpensively available at most labs, even in a doctor’s office. She added that the price range for various operations is $5,000 to $8,000.

She also stated that this is just the beginning and that they are further working to validate the results.

SOBA Could Be Used to Identify Other Disorders, Such as Type 2 Diabetes and Parkinson’s

Dr. Daggett has stated that the FDA has approved their breakthrough status application to develop this test.

According to researchers, the test has further potential because it is theoretically possible to detect other amyloid illnesses using the same technology. Misfolding proteins appear to be associated with Parkinson’s disease, type II diabetes, and Lewy body dementia, suggesting that SOBA could one day be modified to detect early signs of these other diseases.

References

  1. Shea, D., Colasurdo, E., Smith, A., Paschall, C., Jayadev, S., Keene, C.D., Galasko, D., Ko, A., Li, G., Peskind, E. and Daggett, V., 2022. SOBA: Development and testing of a soluble oligomer binding assay for detection of amyloidogenic toxic oligomers. Proceedings of the National Academy of Sciences, 119(50), p.e2213157119.
  2. Neff, R.A., Wang, M., Vatansever, S., Guo, L., Ming, C., Wang, Q., Wang, E., Horgusluoglu-Moloch, E., Song, W.M., Li, A. and Castranio, E.L., 2021. Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets. Science advances, 7(2), p.eabb5398.
  3. Upham, B., New Blood Test Can Identify Toxic Protein Years Before Alzheimer’s Symptoms Appear. Everyday Health. https://www.everydayhealth.com/alzheimers-disease/new-blood-test-can-identify-toxic-protein-years-before-alzheimers-symptoms-appear/. Accessed: 4th Jan, 2023.
  4. Cassela, C., New Blood Test Accurately Predicts Alzheimer’s Years Ahead of First Symptoms. Science Alert. https://www.sciencealert.com/new-blood-test-accurately-predicts-alzheimers-years-ahead-of-first-symptoms. Accessed: 4th Jan, 2023.

FDA has Granted Accelerated Approval for Leqembi

FDA Has Granted Accelerated Approval For Leqembi

Leqembi (lecanemab-irmb), a medication for treating Alzheimer’s, received approval from the U.S. Food and Drug Administration via the Accelerated Approval pathway on January 6th, 2023. Leqembi is the second drug in a newly approved class for Alzheimer’s that addresses the illness’s basic pathophysiology. These drugs are a significant step forward in the ongoing endeavor to find an effective treatment for the disease.

The Accelerated Approval pathway allows the FDA to approve medications for life-threatening illnesses when there is an unmet medical need and that medicine has shown to have an impact on a surrogate endpoint that is relatively likely to predict a clinical benefit for patients.

According to the press release, Billy Dunn, MD, head of the neuroscience division of the FDA’s Center for Drug Evaluation and Research, stated, “This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.”

The approval came following a review of Phase III randomized controlled clinical trial data published in The New England Journal of Medicine in November 2022. The findings demonstrated that Leqembi (lecanemab-irmb, Eisai) lowered amyloid markers in early Alzheimer’s and resulted in less cognitive and functional decline. According to the news release, the agency would soon receive the trial’s results to verify the drug’s clinical benefit. Eisai R&D Management Co., Ltd. received approval for Leqembi.

Results of the Clinical Trials for Leqembi

Researchers assessed the efficacy of Leqembi in a double-blind, placebo-controlled, parallel-group, dose-finding study comprising 856 Alzheimer’s patients. Patients with mild cognitive impairment (MCI) or mild dementia stage of the disease and confirmed presence of amyloid beta pathology underwent treatment.

Patients who received the recommended dose of lecanemab, 10 mg/kilogram every two weeks, saw a considerable time- and dose-dependent reduction in the amount of amyloid beta plaque. It demonstrated a statistically significant decrease in brain amyloid plaque from baseline to Week 79 when compared to the placebo arm, which showed no decline in amyloid beta plaque.

These findings support Leqembi’s Accelerated approval, which is justified by the reported decline in amyloid-beta plaque levels, a sign of Alzheimer’s disease. Researchers quantified the amyloid beta plaque via positron emission tomography (PET) imaging to compare the levels of amyloid beta plaque in a composite of brain regions expected to be severely affected by the pathology of Alzheimer’s to a brain region expected to be spared from such pathology.

Prescribing Information for Leqembi

Leqembi comes with a warning for amyloid-related imaging abnormalities (ARIA), which are known to happen with the antibodies from this class. ARIA is typically asymptomatic, though severe and life-threatening events are rare.

Although some patients may experience symptoms like headache, disorientation, dizziness, altered vision, nausea, and seizures, the most common sign of ARIA is transient swelling in brain regions that often goes away with time.

Besides, there is also a possibility of infusion-related responses, which can cause flu-like symptoms, nausea, vomiting, and changes in blood pressure. Leqembi’s most frequent adverse effects included headache, ARIA, and infusion-related problems.

Leqembi is intended for Alzheimer’s treatment, as stated in the prescribing information. According to the labeling, Leqembi treatment should begin in patients with mild cognitive impairment or mild dementia stage of disease, the population in whom treatment was evaluated in clinical trials. Additionally, the labeling states that there are no safety or efficacy data regarding starting the treatment at earlier or later stages of the disease than were investigated.

References

  1. FDA Grants Accelerated Approval for Alzheimer’s Disease Treatment. FDA News Release. Published online: 6th Jan, 2023. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment. Accessed: 10th Jan, 2023.
  2. van Dyck, C.H., Swanson, C.J., Aisen, P., Bateman, R.J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S. and Froelich, L., 2022. Lecanemab in early Alzheimer’s disease. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2212948
  3. FDA grants accelerated approval for Leqembi. European Pharmaceutical Review. Published online: 9th Jan, 2023. https://www.europeanpharmaceuticalreview.com/news/178331/fda-grants-accelerated-approval-for-leqembi-alzheimers/. Accessed: 10th Jan, 2023.
  4. FDA grants accelerated approval for Alzheimer’s treatment. Healio.com. Published online: 6th Jan, 2023. https://www.healio.com/news/neurology/20230106/fda-grants-accelerated-approval-for-alzheimers-treatment. Accessed: 10th Jan, 2023.