Tag Archives: alAlzheimer’s Disease

Exciting Results from Clinical Trials Prove Monoclonal Antibody Aducanumab Successful in Removing Amyloid

The results of a clinical trial conducted by scientists at Biogen, was recently published in the journal “Nature.” The trial, which lasted for a year, included 165 early-stage Alzheimer’s patients, identified as prodromal or only mildly affected by the disease. The mini mental state examination (MMSE) upon beginning the trial averaged between 23 and 25 across all test groups. The CDR score (clinical dementia) was 1.0 for the mild group and 0.5 for the prodromal group. Researchers wanted to prove the effectiveness of aducanumab, a monoclonal antibody therapy in clearing amyloid (A-beta) plaque from the brain.

The Trial Format

Subjects were divided into five groups according to dose administered: placebo, 1, 3, 6 and 10 milligrams per kilogram of bodyweight. The degree of amyloid removal in patients mildly affected by Alzheimer’s was quite dramatic. The aducanumab antibody did such an efficient job of cleaning the brain of amyloid that the scans of patients who received the highest doses of the antibody were comparable to patients who were defined as having no amyloid.

Side Effectsthe brain

The amyloid clearance results were the most dramatic in the group being given the highest dose (10 mg per kilogram) but the adverse reactions were also the most significant in this group. Overall, the higher the dose, the higher the frequency of adverse events. Those receiving the highest dose experienced as much as a 38 percent adverse rate, which if the drug is approved, would present some challenges to patient managers in treatment over long periods. Lower doses resulted in lower frequencies of adverse events, with only 10 percent needing to be discontinued due to side effects.

Slowing of Cognitive Decline Observed

The degree of cognitive decline during the course of the year was very much tied to the dosage, although there was some decline across all the groups. The placebo group showed the most cognitive decline, slightly less than two points measured by the CDR-SB, whereas those receiving the highest dose showed a cognitive decline of slightly more than .05 points. These results carried over to MMSE too. Once again, the placebo group declined more than 2.5 points by the end of the year, and those receiving 10 milligrams declined around 0.5 points. However, MMSE did not seem to be as dependent upon the dose administered because patients receiving 1 mg were not statistically different than those who received 6 milligrams. These results are similar to the performance of Nilvadipine, small molecule also found to reduce levels of amyloid. Nilvadipine is developed by Archer Pharmaceuticals. A major difference, though, is that Nilvadipine is administered once per day orally, whereas aducanumab must be administered by intravenous injection, one dose per month.
In conclusion, the trial results are good news for Biogen’s researchers. The corresponding reduction in cognitive decline with reduction in amyloid gives further support to the theory that reducing amyloid levels in the brain can be a prevention strategy for Alzheimer’s disease.

Michael Mullan’s A Journey Through the Effects of Alzheimer’s on the Brain Part-3

11 Understanding Plaques 

Plaques are formed when pieces of protein known as beta-amyloid join together. Beta-amyloid is located in larger proteins normally found within the fatty membrane around the nerve cells. 
Beta-amyloid is a sticky in a chemical sense and slowly builds up in the plaques. 
Groups of beta-amyloids of a few pieces or more could be more damaging than the actual plaques. These clumps could inhibit signalling between cells and the synapses. They could also be activating immune system cells which are triggering inflammation and devouring disabled cells. 

12 Understanding tangles 

Tangles are the cause of destruction within essential cell transport systems made up of proteins. The electron microscope images illustrates a cell with hea beta-amyloid Michael Mullanlthy areas along with zones where tangles are beginning to form. 

In the healthy area: 
The transportation system is organized in parallel strands much like railway tracks. Cell parts, food molecules and other essential materials move along these “tracks” 
Proteins called tau help the track to remain straight 
In regions where the tangles are formed: 
Tau proteins collapse into tangles – the twisted strands 
The tracks cannot stay straight, instead the disintegrate and fall apart 
Nutrients and other important supplies cannot move between the cells so they eventually die. 

13 How it Progresses through the brain 

cortex

 

 

 

 

 

Tangles and plaques (indicated by the blue areas) are typically spread throughout the cortex in a fairly predictable pattern as the progression of Alzheimer’s sets in. 

Progression rates vary greatly with some people living an average of just eight years, while others can live for as much as 20 years. The progression rates depend on various factors, including the age when the person is diagnosed and also if they have other existing health problems. 

Early Alzheimer’s – changes could occur anywhere up to 20 years prior to diagnosis. 
Mild Alzheimer’s – in general lasts between two to 10 years. 
Severe Alzheimer’s – can last between one to five years. 

14 Alzheimer’s in its Earliest Stages 

In the earliest Alzheimer’s stages, prior to symptoms being detected with current testing, tangles and plaques start to form in areas of the brain associated with: 

Memory and learning 
Planning and thinking 

15 Mild Alzheimer’s 

In the mild to moderate period, the areas of the brain essential for thinking, planning and memory develop more tangles and plaques than were evident in the early stages. Due to this, individuals can develop problems with thinking and memory that are severe enough to create issues with their normal social and work life. The can become confused and have issues with handling money, collecting their thoughts and expressing themselves. Many people that have Alzheimer’s are initially diagnosed in this stage. 

Tangles and plaques can also spread into areas associated with: 

Speech and interpreting speech 
Your sense of spatial awareness 

As the disease progresses, people can experience a change in behavior and personality while they can also have issues recognizing family members or friends. 

16 Alzheimer’s in severe stages 

Once Alzheimer’s is advanced the majority of the cortex is damaged significantly. The brain size shrinks a great deal following widespread cell death. People with Alzheimer’s lose the ability to recognize their family and friends, the ability to communicate and to take care of themselves.

Read previous chapters Here

Alzheimer’s : Gender Disparities

Alzheimer’s impacts women differently

Old lady

Alzheimer’s disease takes a heavier toll on women

Alzheimer’s, a disease that causes a degeneration in cognitive functioning, including memory and thought processing skills, is affecting 5 million Americans according to 2014 stats from the Alzheimer’s Association. Of these 5 million 3.2 million are women, two-thirds of the total. The disparities continue into the realm of caregiving. Women are more than twice as likely as men to be solely responsible for providing care to an Alzheimer’s sufferer, most commonly her spouse. In fact, it is reported that 65% of all US caregivers are women, who are providing round-the-clock care. So as well as being more likely to succumb to Alzheimer’s, women have a greater chance of being burdened with the intense physical and psychological challenges of caring for an Alzheimer’s patient.

Why the disparity?

A lot of discussion and study has gone into understanding the increased vulnerability of women to Alzheimer’s, but to date no concrete answer has been found. It has been pointed out of course that women generally live longer than men. Alzheimer’s typically manifests around the age of 65, and more women than men tend to live to this age, thereby skewing the statistics. At 65 women face a risk factor of 1:6 whereas men have a risk factor of 1:11. However, this does not give much satisfaction. Researchers are looking at the relationship between the higher risk factor and amyloid regulators such as hormones, and how that may affect women. Hormones such as testosterone and estrogen are known to act as amyloid inhibitors, with the amyloid protein being a causative agent in Alzheimer’s. Therefore, it is theorized that a woman in menopause, whose estrogen levels are radically reduced, no longer has this natural inhibiting agent blocking amyloid production. If true, then preventative strategies such as hormone replacement therapies should succeed in reducing the incidence of Alzheimer’s in older women: however to date this has not happened. Clearly, much more investigation and research is needed.

The Challenge

Alzheimer’s disease takes a heavier toll on women: more develop the disease than men and more are full-time caregivers. Women are less likely than men to receive outside help, burdening them with emotional and physical challenges that negatively impact their health. Future research into the disease must take into account this gender-based factor, and prioritize according.

Reviewing New Research in Treating Alzheimer’s Disease

Synapse in brainIn a recent article discussing the findings of Korean researchers into the use of new drugs targeting Alzheimer’s disease, Lauren Horne discusses how the team may have discovered new information in the fight against the development of the disease. The study, titled “GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease”, is the work of Drs. Daesoo Kim and C. Justin Lee and was published in June of 2014 in the medical journal “Nature Medicine”. The article highlights how the neurotransmitter inhibitor GABA when released in higher dosages through the BESt1 channel has been shown to negatively affect the functioning of synaptic transmission, as well as plasticity, and memory. The research delves into the role that reactive astrocytes play in the development of Alzheimer’s disease, and possibly how it can be treated in the future.

According to the description of the study by Horne, the team in Korea began conducting their tests after discovering that there were large quantities of reactive astrocytes found in the brains of mice who had Alzheimer’s disease. In the course of their research, they found that the reactive astrocytes were creating the GABA transmitters through the enzyme Monoamine oxidase B(MAO-B). When the GABA transmitters were being released through the Bestrophin-1 channel, it was discovered that they were having a suppressive effect on the flow of normal information at the time of synaptic transmission.

In an attempt to reverse the effects of the B(MAO-B) that was being produced by the reactive astrocytes, the researchers utilized B(MAO-B) inhibitors to help return the levels to normal. This result of these changes was made clear in testing performed on mice with Alzheimer’s disease when their memory showed signs of improvement following the treatment. However, the benefits of the treatment using Selegiline as the inhibitor agent were not long lasting. While it has been shown to have positive results in treating Parkinson’s disease, it is unlikely that it will be use long term in treating Alzheimer’s disease.

While this study is only a preliminary entry into this avenue of research, I suspect that it holds great potential for further courses of study into finding a cure to Alzheimer’s disease.

How to Avoid Alzheimer’s Disease

The cognitive decline of an Alzheimer’s disease sufferer is heart-rending to family and friends. This disease is debilitating and as yet, has no certain cure. Although there is also no concrete way of predicting how Alzheimer’s will progress, recent studies show that lifestyle changes may play a significant role in deterring the disease. Preventing the onset of the disease requires therapeutic lifestyle modification early in life thereby reducing risk factors associated with the disease?

The Research

Several studies have been made in which it was concluded that lifestyle changes and social enhancement do indeed play a role in the prevention of Alzheimer’s disease. The Finnish Geriatric Study to Prevent Cognitive Impairment and Disability (FINGER) conducted one such study with astounding results. All the participants selected for the study were at risk for developing Alzheimer’s due to factors like age and heart health not being optimal. Participants were given basic healthcare across the board.

Only half of the participants were given a complete lifestyle make-over and a social support system that included cognitive training, control of risk factors and social activities. When the study ended after two years, these participants were in much better health than their peers who did not benefit from an improved lifestyle and social support. These individuals not only made significant improvement in their chances of avoiding Alzheimer’s disease but also drastically enhanced their quality of life – a win-win situation.

How to Start Making Changes

Try to adapt your lifestyle to make as many of the following changes as possible:
• Decide on a daily exercise regime: Consult a physician to ensure that it is suitable to your current health status.
• Eat healthy: In recent years the so-called Mediterranean diet has become associated with optimum health and considerably lower risk of cognitive decline. It consists of fresh ingredients like vegetables, fish and uses olive oil as the main source of fat. Avoid processed foods, excessive sugar, salt and saturated fats.
• If you smoke, stop. Damaging the brain vessels in any way increases inflammation and the risk of Alzheimer’s as well as many other serious health threats.
• Get enough sleep: Sleep is good for learning and memory and lack of it can seriously impact on your mental functions.
• Take supplements, but not to excess: Deficiencies in Folate and Vitamin B12 have been proven to increase the risk of Alzheimer’s. However, nothing has been conclusively proven in studies conducted on the effects of other vitamins, minerals and fatty acids.
• Finally, avoid impact to your head if possible: It is a known fact that Traumatic Brain Injury (TBI) increases the likelihood of Alzheimer’s. Accidents happen but taking precautions like wearing protective headgear when engaging in sports and investing in anti-slip mats around the home is an excellent practice.

While we cannot as yet cure the disease, it is possible to lower the risk with a lifestyle overhaul. Remember the sooner you adopt a healthier lifestyle, the more likely it is to be an effective preventative measure. Programs like Sci-Brain  that is developed to primarily address an objective way to optimize cognitive outcome based on reducing risk factors associated with Alzheimer’s disease based on Research at the Roskamp Institute.

Ten tips to avoid Alzheimer’s Disease – part 7

Putting it all together.

More than any one particular activity it seems that a lifestyle that encompasses all of the above aspects is required to combat a slip into Alzheimer’s Disease. When looked at together the above recommendations look like a big change in lifestyle for some of us. One important point is that people who incorporate some of all of these aspects into their lives do much better in staving of Alzheimer’s Disease than those that that just adhere to one of them. So the message from the scientific studies is that we should adapt our lifestyles as much as we can in each of these areas to be lower our risk for Alzheimer’s Disease. That can be both challenging and fun especially when undertaken with family or friends. A positive outlook on our ability to defeat Alzheimer’s Disease by our own efforts puts us back in control of our lives and lets us not see ourselves as victims of this disease. The scientific literature more and more suggests there are many ways we can defy Alzheimer’s Disease and the more we do in each of the areas above the more successful we will be. So start now and push back the cognitive clock. Enjoy your new regimen!