Month: September 2023

Every September, people around the world gather to raise awareness about Alzheimer’s disease and other dementias. Everyone is encouraged to participate in World Alzheimer’s Month, from individuals to major organizations, including all the world’s Alzheimer’s and dementia associations.

Alzheimer’s Disease & Dementia

Alzheimer’s disease is the most frequent cause of dementia, accounting for 60-70% of dementia cases. It is a neurological illness that worsens with time and impacts memory, thinking, and behavior. It results in significant cognitive decline and loss of independence. Even though age is the primary risk factor, Alzheimer’s is not a typical aspect of aging. Genetics, lifestyle factors, and general well-being can all play a role in the disease’s progression.

World Alzheimer’s Day and its Significance

The goal of World Alzheimer’s Day, which is commemorated on September 21st each year, is to increase public understanding of Alzheimer’s disease and other dementias while also addressing the stigma associated with them. It is critical to increase public awareness and offer assistance to those affected by dementia because there are more than 50 million people living with it worldwide, and millions more are being diagnosed each year.

World Alzheimer’s Day provides a valuable opportunity to increase awareness, dispel myths, and promote knowledge of the illness. We can eliminate the stigma that often isolates people with dementia and their families by encouraging discussions and information sharing. This worldwide event also provides a forum for governments, organizations, and individuals to work in tandem on research, preventive, and care activities.

Alzheimer’s Day Theme 2023: Never Too Early, Never Too Late

Every year, for its campaign, Alzheimer’s Disease International (ADI) typically selects a theme. It was ‘never too early, never too late’ this year.

The “Never Too Early, Never Too Late” campaign emphasized the critical need to determine risk factors and implement proactive risk reduction strategies to delay and possibly even prevent the development of dementia. It also covered ongoing risk reduction measures for people who have already gotten a diagnosis.

People are becoming more aware of the importance of brain health interventions and the fact that Alzheimer’s and other dementias can start years before symptoms appear. With the worldwide dementia population anticipated to triple by 2050, there has never been a greater pressing need to identify and address the risk factors linked with this condition.

A new campaign toolkit, new accompanying guides, a dementia fact sheet, and materials for organizing events to raise awareness and money for the cause were all included in this year’s World Alzheimer’s Month campaign materials. These materials were available in English, French, and Spanish.

How can you participate in World Alzheimer’s Day?

You can support World Alzheimer’s Day in a variety of ways and improve the lives of people with dementia. The following suggestions will help you get started:

• Share your experience: If you or a loved one has been impacted by Alzheimer’s, talking about your circumstances might make others feel less alone and promote understanding. Discuss your adventure with friends and family, on a blog, in a video, or simply by talking to them.
• Raise awareness: Post information about World Alzheimer’s Day and instructional materials on social media. Additionally, you can organize or go to nearby gatherings like workshops, seminars, or support groups.
• Fundraise: To raise money for Alzheimer’s research and support services, organize a charitable event such as a bake sale, fun run, or quiz night. For the most impact, be sure to register your event with an established organization like Alzheimer’s Research Association.
• Volunteer: Offer your time and expertise to a nearby dementia support group or care home by volunteering. You can offer companionship, assistance with activities, or support with office work.
• Make a change: Speak up for more funding and support for Alzheimer’s research, care, and prevention by contacting your local legislators. Keep up with changes in policy and express your opinions.

Support Alzheimer’s Research

Supporting research and prevention initiatives is crucial for having a long-lasting impact in the battle against Alzheimer’s. Here are a few ways you can contribute:

• Take part in research: If you or a loved one has Alzheimer’s disease, consider signing up for clinical trials or research studies to aid in the creation of novel medications and treatments.
• Financially contribute to research organizations: Support trustworthy organizations dedicated to funding ground-breaking discoveries and breakthroughs in the field of Alzheimer’s.
• Encourage a healthy lifestyle for the brain: Living a healthy lifestyle can lower Alzheimer’s risk. To support cognitive health, encourage others to eat a balanced diet, exercise regularly, maintain their social lives, and pursue lifelong learning.

World Alzheimer’s Day provides a significant opportunity for people to gather in the battle against Alzheimer’s and dementia. You can significantly improve the lives of millions of people worldwide by spreading awareness, helping those who are affected, and funding research and prevention initiatives. Participate, tell your experience, and help change the future of Alzheimer’s.

References

1. Never too early, never too late. Alzheimer’s Disease International. https://www.alzint.org/get-involved/world-alzheimers-month/never-too-early-never-too-late/. Accessed: 27th Sep, 2023.
2. World Alzheimer’s Day 2023. SDG Resource Centre. https://sdgresources.relx.com/events/world-alzheimers-day-2023. Published Online: 21st Sep, 2023. Accessed: 27th Sep, 2023.
3. World Alzheimer’s Day 2023: Know Theme, History And Significance Of The Day. NDTV. https://www.ndtv.com/health/world-alzheimers-day-2023-know-theme-history-and-significance-of-the-day-4406259. Published Online: 21st Sep, 2023. Accessed: 27th Sep, 2023.

CRISPR-Cas9, the Nobel Prize-winning gene-editing technology discovered by Jennifer Doudna and Emmanuelle Charpentier, is on the verge of entering clinical trials for Alzheimer’s disease. However, experts emphasize addressing the obstacles and wonder if scientists are rushing too hastily.

In July 2023, at the Alzheimer’s Association International Conference (AAIC), researchers from the University of California San Diego (UCSD) and Duke University School of Medicine presented two strategies to utilize CRISPR to prevent and treat Alzheimer’s in Amsterdam.

Brent Aulston’s team at UCSD targets APP.

Brent Aulston’s team at UCSD is utilizing CRISPR to alter the amyloid precursor protein (APP). AAP is a transmembrane protein expressed in numerous bodily tissues but mainly exists in the synapses of neurons. Aulston stated that human populations have shown that all hereditary factors contributing to Alzheimer’s impact how APP is processed. One or two enzymes physically cleave APP inside the cell. Alpha secretase is the first one of these enzymes. The breakdown of APP via alpha-secretase cleaves releases a protective molecule known as secreted APP-alpha. The bulk of APP in healthy individuals breaks down to create secreted APP-alpha. In Alzheimer’s patients, however, APP is driven into the opposite cleavage pathway, mediated by beta-secretase. As a result, it produces toxic fragments of amyloid-beta peptides. Aulston’s team is leveraging CRISPR technologies to modify the APP gene to get more alpha and fewer beta cuts. Aulston stressed that the goal is not to eliminate the APP protein entirely. He claimed that this protein plays a crucial role in the brain and performs various tasks. When removed from a mouse, the mouse shrinks, their brains shrink, there is increased neuroinflammation, and their cognitive function is impaired. Therefore, its expression should continue. So, to prevent the resultant protein from coming into contact with beta-secretase, the researchers devised their CRISPR to edit only a short piece of APP. Upon testing the strategy in mice, the researchers discovered that the animals had less amyloid-beta plaques and indicators of brain inflammation but higher levels of the neuroprotective APP. The mice also improved in behavioral and neurological symptoms.

Aulston believes their possible therapy technique is both safe and effective in mice.

Researchers from Duke University School of Medicine target APOE

Duke University School of Medicine researchers are employing CRISPR-Cas9 gene editing to reduce the expression of the APOE ε4 gene, which is associated with an elevated risk of Alzheimer’s. An estimated 15% to 25% of people have this variant, while up to 5% possess two copies. Ornit Chiba-Falek, professor of neurology at Duke University, division chief of translational brain sciences, and senior author of the study presented at AAIC, agreed with Aulston that the goal is to fine-tune the levels of the various APOE variants rather than completely eliminating the protein, which aids in transporting cholesterol and other types of fat in the bloodstream. For instance, APOE ε2 might offer some defense against Alzheimer’s, whereas APOE ε3, the most prevalent form, is thought to have no effect on the condition. The goal of the Duke team is to lower the synthesis of the APOE ε4-encoded protein.
According to the authors of the abstract presented at AAIC, the platform proved effective and precise in altering APOE ε4 and APOE expressions in humanized mouse models and miniature brains made from human induced pluripotent stem cells (hiPSC) from an Alzheimer’s patient. Additionally, they added, there has been no discernible editing of the ε3 allele in the isogenic hiPSC-derived neurons as a result of the precise targeting of the ε4 allele. Chiba-Falek and Boris Kantor, associate research professor of neurobiology at Duke and the study’s lead author, co-founded a biotech firm, CLAIRIgene, to expand and develop the platform, and Chiba-Falek said they are looking at potential partnerships with the pharmaceutical sector. Next are IND-enabling investigations, which, according to her, will concentrate on safety, administration route, and durability.

What are the challenges?

Aulston claimed that his team had reached the top of the first mountain after proving the notion of APP editing. They are currently at the base of the translational side of the other mountain. Treating a human brain is a little more challenging than treating a little mouse.

Professor Gerold Schmitt-Ulms, who studies Alzheimer’s, tauopathies, and prion illnesses at the University of Toronto, stated his reservations regarding the applicability of CRISPR to neurological disorders. According to him, the technology is “lagging behind” other gene therapy strategies in this field for two key reasons: immunogenicity and problems with delivery.

Schmitt-Ulms addressed the first concern by stating that the adeno-associated virus (AAV) capsids utilized in the delivery of the CRISPR machinery will cause an immune response that may reduce the efficacy of the treatments. According to him, around 70% of people have had exposure to natural AAVs, and as a result, we all have antibodies in our blood that would destroy AAV-based gene therapy vectors. CRISPR enzymes are also unknown to the body. They act as foreign agents; if expressed, your immune system will become more sensitive to them. Most current gene therapy clinical studies for neurodegenerative illnesses include the delivery of a specific overexpressed protein. The body is familiar with these proteins. For instance, the body is aware of APOE ε2 and won’t react negatively to it.

To date, no one has been able to deliver such gene therapies to every human brain cell. The best one can hope for right now is that the therapeutic virus only infects a small percentage of brain cells. Frequently, though, that is insufficient to bring about the desired result.

Tanzi stated that he thinks CRISPR should only be used in exceptional circumstances, such as for those who carry two copies of APOE ε4.

References

1. McKenzie, H. CRISPR Shows Preclinical Promise in Treating Alzheimer’s, Challenges Persist. BioSpace. https://www.biospace.com/article/crispr-shows-preclinical-promise-in-treating-alzheimer-s-but-challenges-persist-/. Published Online: 21st Aug, 2023. Accessed: 12th Sep, 2023.

Time-restricted feeding, also known as intermittent fasting, involves limiting the energy consumed to specific times of the day and fasting the rest of the time. According to a recent study, time-restricted feeding enhanced cognition and decreased Alzheimer’s pathology in the brain in a mouse model.

Alzheimer’s disease, the most prevalent type of dementia, is a progressive and eventually fatal neurological disorder. Despite the massive research to find its precise underlying causes and treatment, its proper cure remains unknown.

Current treatments available can assist in relieving symptoms such as memory loss, sleep problems, and behavioral concerns. Donanemab, aducanumab, and lecanemab, three more recent monoclonal antibody medications that remove amyloid plaques (the hallmarks of Alzheimer’s), perform well in clinical trials. However, due to ongoing research, these are not yet generally accessible. Lifestyle changes are another strategy for alleviating Alzheimer’s symptoms.

According to a laboratory study, time-restricted feeding rectifies the circadian abnormalities caused by Alzheimer’s, enhances cognition, and lessens the buildup of amyloid, a protein linked to the development of dementia [1].

A recent mouse model study from the University of California San Diego School of Medicine published in Cell Metabolism revealed that intermittent fasting, or time-restricted feeding, may assist patients with Alzheimer’s [2].

What is Intermittent Fasting?

Intermittent fasting or time-restricted feeding entails whole or partial food abstinence. Methods include eating only during a specific time daily or fasting one or more days every week while eating regularly on the other days.
Although there is little study on intermittent fasting in humans, numerous studies are underway due to its supposed several health advantages.

Weight loss, a lower risk of type 2 diabetes, better heart health, a lower risk of some malignancies, and better brain function are all possible benefits.

Previous mice research has connected time-restricted feeding to gene modifications, longer life spans, and a lower risk of developing cancer [4]. According to the most recent study, time-restricted feeding in mice reversed the circadian abnormalities caused by Alzheimer’s disease.

Circadian disturbances and Alzheimer’s

Circadian disruptions, such as irregular sleep patterns and trouble falling or staying asleep, are common aspects of Alzheimer’s and frequently start before the disease has fully developed.

According to research, there is a bidirectional association between circadian abnormalities and the pathology of Alzheimer’s disease [5]. Circadian rhythm modifications cause protein buildup and other modifications linked to neurodegeneration. Additionally, dysfunctional circadian rhythms are a result of neurodegenerative alterations.

Alterations in activity patterns in models of Alzheimer’s

Transgenic mice designed to develop the pathology of Alzheimer’s and wild-type mice were both used by the researchers in the latest study.

The researchers randomly separated the mice into two groups, each with some transgenic and some wild-type mice. All the mice were accustomed to 12 hours of darkness and 12 hours of light.

The transgenic Alzheimer’s disease mice had disturbed sleep patterns and irregular activity rhythms, and they were considerably more active at night than the wild-type mice.

One group had access to food continuously, whereas the other only had it available for six hours each day during the 12-hour light period. Both groups consumed equal amounts of food despite the different food availability, and there were no apparent changes in body weight between them. The researchers assessed the mice’s cognitive function via the novel object recognition test (NOR) and eight-arm radial arm maze (RAM) methods. They also collected blood samples from the mice for investigation.

They euthanized the mice at the end of the experiment and examined their brains to determine changes in gene expression and the degree of amyloid buildup.

Benefits of time-restricted feeding

Time-restricted feeding reduced blood glucose levels in all mice and altered gene expression in Alzheimer’s mice, curtailing the expression of genes associated with neuroinflammation and regulating clock-controlled genes. The researchers investigated the effect of time-restricted feeding on behavior in Alzheimer’s disease mice after 3 months. They discovered that males and females had different impacts, with only females enhancing total sleep. Both sexes experienced enhanced sleep onset and decreased hyperactivity.

Compared to mice with unlimited food, the Alzheimer’s disease animals on time-restricted feeding showed considerably fewer amyloid plaques. According to the researchers, time-restricted eating may minimize amyloid accumulation while increasing the amyloid elimination rate.

Additionally, the mice receiving time-restricted feeding displayed enhanced cognitive and memory abilities. Before time-restricted eating, the Alzheimer’s disease mice scored lower than wild-type mice in the NOR and RAM tests. When given time-restricted feeding, they performed better on both tasks than Alzheimer’s disease mice who had unlimited food. The cognitive function of the Alzheimer’s disease mice on time-restricted feeding increased to nearly identical levels to those of the wild-type mice.

What’s next?

Even though the study involved mice, and results from studies on animals can be challenging to extrapolate to studies on humans, it offers a solid framework for considering how intermittent fasting may impact Alzheimer’s disease in people. Given the potential benefits of intermittent fasting for neuroprotection and metabolic health, it is logical to assume that there will be similar effects in people.

The study’s researchers believe that intermittent fasting could be a simple method to help patients with Alzheimer’s with their circadian issues, which is one of the primary reasons they require residential care. If researchers can replicate these findings in humans, this strategy could be a simple approach to drastically enhance the lives of patients with Alzheimer’s and their caregivers.

References

1. Vetter, C., 2020. Circadian disruption: What do we actually mean?. European Journal of Neuroscience, 51(1), pp.531-550.
2. Whittaker, D.S., Akhmetova, L., Carlin, D., Romero, H., Welsh, D.K., Colwell, C.S. and Desplats, P., 2023. Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease. Cell Metabolism
3. Deota, S., Lin, T., Chaix, A., Williams, A., Le, H., Calligaro, H., Ramasamy, R., Huang, L. and Panda, S., 2023. Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals. Cell metabolism, 35(1), pp.150-165.
4. Pan, X., Taylor, M.J., Cohen, E., Hanna, N. and Mota, S., 2020. Circadian clock, time-restricted feeding and reproduction. International journal of molecular sciences, 21(3), p.831.
5. Li, P., Gao, L., Gaba, A., Yu, L., Cui, L., Fan, W., Lim, A.S., Bennett, D.A., Buchman, A.S. and Hu, K., 2020. Circadian disturbances in Alzheimer’s disease progression: a prospective observational cohort study of community-based older adults. The Lancet Healthy Longevity, 1(3), pp.e96-e105.
6. Could time-restricted eating help manage Alzheimer’s symptoms? Medical News Daily. https://www.medicalnewstoday.com/articles/intermittent-fasting-time-restricted-eating-alzheimers-disease#Why-might-intermittent-fasting-cause-improvements. Published Online: 29th Aug, 2023, 7th Sep, 2023.

Researchers have developed a method that can predict if someone will experience dementia within the next 14 years using the 11 dementia risk variables they have discovered. In British populations, the score has an accuracy of up to 80%. According to the researchers, it might serve as a preliminary dementia screening technique.

Dementia is a neurological disorder that impacts memory and cognitive abilities and affects millions of individuals worldwide. Since dementia is currently incurable, preventative measures are essential to minimize its effects on an individual’s overall wellness and quality of life.

Researchers have been trying to discover models that could predict dementia years before its onset. Such a model that can predict with a higher accuracy can help in preliminary screening of the condition among individuals.

Researchers from Oxford University and other institutions have made one such attempt and created a dementia risk score comprising 11 risk factors that can identify up to 80% of cases of dementia 14 years before symptoms appear [1]. They dubbed it the Biobank Dementia Risk Score (UKBDRS).

What Previous Studies Have Indicated

Studies indicate that addressing 12 critical risk factors, such as poor levels of education, smoking, and hypertension, could prevent up to 40% of dementia cases [2].

Although several predictive models predict dementia risk, they frequently have substantial flaws. For instance, just eight of the 61 dementia risk scores examined in a systematic review have been verified by external samples [3]. The performance of individuals who had undergone external validation was frequently subpar and inconsistent. Furthermore, the majority of the developmental groups were from North America. It is still unknown if these risk scores apply to other populations.

The Current Study: The 11 Key Dementia Risk Factors

For the study, the researchers looked at medical records from 220,762 people with an average age of 60 who were part of the UK Biobank. They followed the individuals for 14 years.

They also generated a list of 28 dementia-related risk and preventive factors. They identified the following 11 risk factors that substantially predicted dementia risk after examining 80% of the healthcare data from the UK Biobank considering these variables.

• Age (typically 65 and older)
• Lack of education
• History of diabetes
• History of/current depression
• History of stroke
• Parental history of dementia
• Economic disadvantage or poverty
• Hypertension (High blood pressure)
• High cholesterol
• Living alone
• Being male

The researchers initially compared them to the remaining 20% of the UK Biobank data to test the validity of these risk factors. They discovered that the UKBDRS accurately predicted the incidence of dementia in 80% of people.

They then examined external data from the Whitehall II research, which comprised 2,934 British civil officials with an average age of 57 at the start of the analysis, to test the risk score. They followed these individuals for 17 years. In the end, they discovered that the UKBDRS accurately predicted 77% of the dementia cases in this cohort.

According to sensitivity testing conducted by the researchers, the UKBDRS was the most accurate predictor of whether someone would experience dementia within the next 14 years.

They also stated that the UKBDRS produced equivalent results to APOE testing, which evaluates the presence of a significant genetic biomarker for dementia.

APOE testing forecasted 83% of dementia cases in the UK Biobank sample and 79% in the UK Whitehall II research.

The UKBDRS performed better than three other widely used dementia risk scores that had previously received external validation.

What are the limitations of the study?

According to the Medical News Daily, Dr. Joyce Gomes-Osman, vice-president of interventional therapy at Linus Health and physical therapist (who was not involved in the study), lauded the study’s “rich and unique” cohorts and meticulous methods. However, she pointed out that the results are limited because dementia was not identified in the population using gold-standard clinical procedures or evaluations [4].

The availability of hospital records and self-reported outcome indicators varied significantly between the two study groups, which is a further limitation.

While speaking to the Medical News Daily, Dr. Howard Pratt, a board-certified medical director at Community Health of South Florida (CHI) and a non-participant in the study, also highlighted the limitations. He stated that it is limited to the measures under consideration. However, because we don’t know what causes dementia, we don’t know if we’re asking all the appropriate questions or analyzing all the proper indicators while assessing dementia risk.

Can the UKBDRS Tool Help Diagnose and Prevent Dementia?

The UKBDRC may be helpful for preliminary screening, according to Dr. Katherine Ornstein, professor and director of the Center for Equity in Aging at the Johns Hopkins University School of Nursing and a non-participant in the current study.

According to her, high-risk people might undergo extra testing, such as genetic or cognitive testing.
She added that another advantage of the tool is that it might assist people and medical professionals in identifying and changing healthy behaviors before the first symptoms of dementia appear.

References

1. Anatürk, M., Patel, R., Ebmeier, K.P., Georgiopoulos, G., Newby, D., Topiwala, A., de Lange, A.M.G., Cole, J.H., Jansen, M.G., Singh-Manoux, A. and Kivimäki, M., 2023. Development and validation of a dementia risk score in the UK Biobank and Whitehall II cohorts. BMJ Ment Health, 26(1).
2. Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., Brayne, C., Burns, A., Cohen-Mansfield, J., Cooper, C. and Costafreda, S.G., 2020. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396(10248), pp.413-446.
3. Hou, X.H., Feng, L., Zhang, C., Cao, X.P., Tan, L. and Yu, J.T., 2019. Models for predicting risk of dementia: a systematic review. Journal of Neurology, Neurosurgery & Psychiatry, 90(4), pp.373-379.
4. The screening tool uses 11 risk factors to predict dementia with up to 80% accuracy. Medical News Daily. https://www.medicalnewstoday.com/articles/screening-tool-uses-11-risk-factors-to-predict-dementia-with-up-to-80-accuracy. Published Online: 31st August, 2023. Accessed: 1st September, 2023.
5. Will you develop dementia? These 11 factors are strong predictors in middle age, scientists say. Fortune Well. https://fortune.com/well/2023/08/24/11-risk-factors-predict-dementia-middle-age/. Published Online: 25th August, 2023. Accessed: 1st September, 2023.
6. A dementia risk study finds 11 key factors behind the condition. The Guardian. https://www.theguardian.com/society/2023/aug/24/dementia-risk-study-finds-11-key-factors-behind-condition. Published Online: 24th August, 2023. Accessed: 1st September, 2023.