Vascular damage and Alzheimer’s disease
December 21, 2012In our last entry we discussed the poor understanding that the scientific community has on how and why people develop Alzheimer’s disease. Most scientists have been wedded to the idea that accumulation of a molecule termed “amyloid peptide” in the brain is the main cause of the disease, even in the face of overwhelming evidence showing that such accumulation is a consequence, rather than a driver, of the disease. We were encouraged by the publication of two articles proposing that cholesterol abnormalities and/or inflammation might be very early events in the development of Alzheimer’s disease and therefore promising targets for the pharmaceutical industry.
Now, scientists from the Salk Institute in La Jolla have published data supporting the notion that the vascular system in the brain might be the first to fail in people with Alzheimer’s disease. This idea makes a lot of sense, because the vascular system supplies the brain with nutrients and, at the same time, keeps toxic molecules out of it, so if it becomes leaky or otherwise faulty it could potentially lead to metabolic abnormalities and toxin accumulation, eventually resulting in the pathology that is seen in the Alzheimer’s brain. Therefore, it would be reasonable to explore how and why the vascular system in the brain can deteriorate, because if we can address those issues we can potentially prevent the damage that occurs at later stages of the disease.
With that context in mind, we encourage you to read this new article, which makes use of a mouse model of accelerated aging to confirm a central role for the integrity of the vascular system in preventing the unwanted effects of aging in the brain. Those of you interested in understanding the molecular events that are likely to be involved in how Alzheimer’s disease develops in the general population will find it highly enjoyable.
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As the amyloid hypothesis keeps failing, two new scientific proposals to explain Alzheimer’s disease
December 11, 2012The so-called amyloid hypothesis has led researchers for many years now in search of a cure for Alzheimer’s disease. After billions of dollars spent and several dozen failed clinical trials, it is clear that alternative ideas are needed in the field if we want to understand, let alone find a way to stop, the disease. Helpfully, two new articles offer outside-the-box ideas on how Alzheimer’s disease may begin and what those ideas might mean in terms of finding a cure. It has been known for a long time that both cholesterol abnormalities and inflammatory reactions in the brain are common in the Alzheimer’s disease brains. Now, scientists from Loma Linda University and from the University of Zurich have proposed models of neurodegeneration in which either cholesterol abnormalities or inflammation may explain why and how people may develop Alzheimer’s disease.
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Schizophrenia misunderstood?
August 15, 2012We wrote an overview some time ago about the social stigma that schizophrenia sufferers have to go through. We mentioned how understanding what schizophrenia is from a medical standpoint would help with the goal of getting the general public familiarized with this condition. Once that goal is attained, fear and rejection of people with schizophrenia will be less likely.
Now there is a very insightful post from Paris Williams on brainblogger.com that discusses the possibility that schizophrenia may not even be a disease, but (summarizing) a physiological response to “existential dilemmas”. Explaining what that means in terms of defining schizophrenia is not easy, and the author has written a whole book on the subject. The main point, however, is that her line of thinking offers a welcome fresh perspective on the nature of the disease, one that is far from the more obscure medical terms that quite often people associate with darkness and fear and that are not useful any longer.
Posted in Schizophrenia | Tagged National Institutes of Health, schizophrenia, stigma |Leave a comment
Alzheimer’s disease research: are we heading in the wrong direction?
August 7, 2012New scientific results suggest that the current wisdom regarding what causes Alzheimer’s disease is probably wrong. It is widely thought that a molecule called amyloid is responsible for the brain damage that occurs in Alzheimer’s disease. This idea is called the amyloid hypothesis, and huge efforts are being made to find ways to reduce the amount of this molecule in the brain. According to scientists, the less amyloid we have, the smaller the chance of getting the disease.
The pharmaceutical industry, from small start-up companies to huge multinational conglomerates, have placed all their chips on this idea for more than a decade now, and the results have been an unqualified disaster. They have been able to reduce the amounts of amyloid in the brain but, surprisingly, with no therapeutic benefits at all and, in some cases, with additional damage done to patients. In addition to that, new evidence keeps accumulating from molecular, cellular, animal and human studies that suggests that the amyloid hypothesis might indeed be wrong, and amyloid itself is likely to be a secondary player, that is indeed present in the brain, but only as a response to the real bad guys that cause the disease.
So we have a long-term lack of success in clinical trials as well as scientific evidence from multiple sources showing that amyloid is not an early source of damage in the Alzheimer’s brain. Accordingly, the sensible thing to do would be to put amyloid-based clinical trials on hold and direct more resources towards trying to understand the mechanisms that lead to the disease.
Posted in Alzheimer's Disease, Disease Center | Tagged Alzheimer's disease, amyloid, clinical trials, dementia, mental health decline |2 Comments
Synesthesia or the curious world of the mixed senses.
June 11, 2012“When I’m reading I can see that what I’m looking at is in black and white, but I also see
the ‘correct’ colors for the letters and symbols.”
“I may call someone ‘Debbie’ when she is really ‘Paula’, because D and P are more or less
the same color green.”
“Tuesday is yellow. I don’t ‘see’ it anywhere in particular; rather, I have a general
awareness of yellowness in relation to the word.”
“I avoid middle C when I play the piano, because it has an earthy, musky smell I don’t like.”
These statements were made to scientists by people who were genuinely describing what was going on in their minds. Do they look familiar to you? If so, you may have synesthesia, a condition in which stimulation of one sense evokes the response of a different sense, and that affects 2-4% of the general population.
These experiences are so odd and subjective that, until very recently, doctors and scientists considered that the people who faced them (called synesthetes) were mentally ill, and it was not unusual for them to be diagnosed as schizophrenics and be locked up in mental institutions.
With the advent of more sophisticated methods of research and better insight from scientists, this situation has changed and synesthesia is now widely accepted as normal and it even has the potential to take us closer to understanding how the human brain works. This is because scientists have known for a long time that the brain is divided into different functional areas, which are independent of each other. We are all familiar with cases in which someone suffers brain trauma that leads to loss of one function (i.e. memory, vision, etc) leaving other functions and skills untouched. In other words, it seems that different parts of the brain are self-sufficient and do not normally interact with each other.
Research on synesthesia has allowed scientists to understand this idea better, because brain areas in synesthetes appear to be able to “talk to each other” in a way that non-synesthetes can’t. That unique “skill” is great news for scientists, as it allows them to have a peek at how this unusual talk amongst different parts of the brain occurs.
As is usually the case in science, progress has been slow, and it will take a while before we are aware of how exactly synesthesia occurs and what it teaches us about the brain. Currently, scientists are divided between those who think that
1) Synesthetes have “crossed wires” in the brain (i.e. faulty connections that lead to seeing smells and so forth) or
2) All brain areas are fully connected and in normal people those connections are actively isolated from each other. In synesthetes, some sort of molecular glitch prevents that isolation from happening, and areas of the brain that are normally closed to each other are now in contact. But the main idea here is that the brain structure of synesthetes is not faulty or abnormal.
There are other ideas being proposed by scientists, but they are usually variations or combinations of one of these two.
Regardless of who turns out to be right, it is inspiring that common sense has prevailed and synesthetes don’t have to fear “coming out”. Too often, seemingly odd behaviors or unusual brain skills are associated with stigmas that ruin lives. Some of those stigmas are easier to drop (i.e. it can be “cool” that one can smell music and hear colors); others not so much, as we pointed out earlier for schizophrenia and other disorders.
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Stem cell therapy will not cure Alzheimer’s disease
March 1, 2012Researchers from the University of California at San Diego have been able to isolate stem cells from Alzheimer’s disease patients and made them behave like neurons.
This is a great scientific feat that will help the research community understand better the mechanisms by which the Alzheimer’s brain deteriorates. It has also generated some media buzz about how stem cell therapy may one day cure this devastating condition. Unfortunately, that is extremely unlikely to happen, and here’s why:
Stem cell therapy involves replacing damaged or injured cells with new ones, called stem cells, which have the ability to become identical to the cells they are replacing. The supply of stem cells is unlimited and, because they originate from the person suffering the injury or the disease, there are no concerns about immune rejection. This sort of therapy can lead to a dream scenario where people can tap into their own stem cell reservoir any time a major disease or an injury strike and replace damaged or dead cells with new ones.
Stem cell therapy is in fact already working in many cases and is likely to be successful in many more, but it simply cannot work with Alzheimer’s disease, because of the unique properties of the cells that are injured and that die in this condition. Perhaps this will be best understood if we compare it with Parkinson’s disease, in which stem cell therapy is likely to succeed. What happens in Parkinson’s is similar to Alzheimer’s disease in that there is massive death of neurons, but in the Parkinson’s case those neurons are in charge of one thing: coordinating movement skills. This is a relatively simple task, more or less mechanical in nature, and it is not difficult to see how one could replace dead or injured neurons with new ones that will do the same job and will help sufferers recover their movement skills.
Now compare this with what happens to Alzheimer’s disease sufferers. Their problem is not a loss of movement skills or any other relatively basic function. What they lose is cognitive function, mental sharpness, intelligence, senses of irony, sadness, happiness…In short, they lose the essence of who they are, and that essence is defined mostly by the unique connections and interactions amongst brain cells, not by the actual cells themselves. Because those connections are created and evolve as a consequence of life experiences that are obviously unique to each of us, once the cells die and the connections are lost, we cannot get them back, unless we could live the same life all over again with the newly replaced cells. Obviously, that does not make sense, and therefore neither does attempting to use stem cell therapy to cure Alzheimer’s disease.
All of this is not to say that stem cell research is not a good thing. It is in fact a great research tool, which, together with many others already in place, will help us understand how the brain deteriorates in Alzheimer’s disease. But it will not cure Alzheimer’s disease. If we want to do that, we need to understand what happens in the brain BEFORE it begins to deteriorate, so we can have intervention strategies at that stage. Unfortunately, and as we wrote in our previous post here, that is unlikely to happen any time soon and Alzheimer’s disease is well on its way to becoming the plague of the XXI century.
Posted in Alzheimer's Disease, Disease Center | Tagged Alzheimer's disease, dementia, mental health decline, Neurostrong, stem cell therapy |1 Comment
The tragic state of affairs in Alzheimer’s disease research
February 3, 2012The federal government recently set the goal to have a treatment for Alzheimer’s disease (AD) by the year 2025. Given the large amount of resources that are allocated to investigating the disease, it seems a reasonable goal. There is one problem though. Research in the AD field has been stuck in neutral for a very long time and seems now determined to go in reverse, all the way to where it started 20 years ago, when the modern tools of science were first applied to the problem. It would almost be comical if it were not for the tragic consequences, social, emotional and financial, not only to the sufferers and their families, but to society in general, that are associated with this devastating condition.
So why are we heading in the wrong direction? Let us go over the facts. Over two decades ago, researchers found that the Alzheimer’s brain had two distinct pathological features, which they called senile plaques (SPs) and neurofibrillary tangles (NFTs). Both are sticky masses in the brain that are thought to interfere with its function and eventually kill brain cells, causing the symptoms of dementia.
Researchers quickly came up with the amyloid hypothesis to explain how SPs and NFTs might cause damage in the AD brain. The hypothesis is so called because a peptide called amyloid accumulates over time and aggregates into the sticky masses that are the SPs. In a nutshell, this hypothesis states that the amyloid peptide initiates the disease, leading to the formation of NFTs and the death of brain cells. It was thought that, if one were able to remove amyloid from the brain, one would cure the disease. In those early days, there was good genetic and biochemical evidence to support that strategy, and almost every research dollar available ever since has been poured into it. The problem is that, 20 years and billions of dollars later, that strategy has been proven to be a waste of time and resources.
How so? In clinical trials with drugs designed to reduce the amount of amyloid in the brain, patients do indeed show significant decreases in amyloid (meaning that the drug did what it was supposed to do), and yet the patients do not show any improvement; if anything, they deteriorate faster.
If that were not enough to convince people that SPs are not the be-all and end-all of AD, here’s another fact: it turns out that SPs are present in 20-40% of people with no cognitive problems, let alone signs of dementia. So one does not have to be a brain scientist to see that we should not be aiming to cure AD by targeting SPs as the bad guys.
It is much more likely that SPs are the consequence, not the cause, of the condition. Imagine the progression into Alzheimer’s disease as a battle between the brain and stress factors in which amyloid is the brain’s weapon and the stress factors are the enemy that will eventually cause the disease. Amyloid accumulates over time as a consequence of the continuous battle in the brain, eventually aggregating into the sticky masses that are the SPs. In other words, SPs would be the “corpses” in the battlefield after the war against AD. That would easily explain the failure of clinical trials designed to remove amyloid from the brain (because they are effectively depleting the brain’s defenses). It would also explain the presence of SPs in non-demented individuals, in whom the battle against AD took place and “the brain won”.
The above scenario has not been proven, but it does account for the current known facts better than the amyloid hypothesis does. But here’s the problem: the lion’s share of research funds is still allocated to scientists who base their research on the assumption that amyloid is the main cause of Alzheimer’s disease, despite the overwhelming evidence to the contrary. These are the most influential scientists, the ones who currently make the key decisions about what research gets published and funded. Perhaps they are too invested intellectually and/or financially in the outcome of research and clinical trials based on amyloid biology. Whatever the reason, the current situation is not acceptable; we need to give breaks to scientists who come up with reasonable alternative ideas to study AD. This is not happening.
Instead of taking a few steps back and making funding decisions based on objective evidence, it seems as if the leading scientists are doubling down on the amyloid hypothesis. That is bad science and it will bring devastating consequences, as Alzheimer’s disease slowly but surely turns into the biggest medical problem of our time.
Posted in Alzheimer's Disease, Disease Center | Tagged Alzheimer's disease, amyloid, clinical trials, dementia, mental health decline |7 Comments
Aspirin in the fight against Alzheimer’s disease
January 25, 2012Aspirin has been touted as the closest thing to a magic bullet in medicine. The scientific literature is full of high profile peer reviewed articles showing that aspirin, if taken daily, can help prevent, among others, stroke, cancer and Alzheimer’s disease. So, if the science is sound, why isn’t it more actively promoted as a daily intake wonder drug? The cynics will tell you that, at a cost to the consumer of about 2¢ per pill, there is no good economic argument for promoting it. But, to be fair, aspirin can have serious side effects to some people at risk, the best known of which are gastrointestinal bleeding and hemorrhagic stroke, so encouraging the general population to take a daily dose of aspirin, while of likely great benefit to many, will also pose dangers to at least some.
Aspirin belongs to the family of non-steroid anti-inflammatory drugs (NSAIDs). Because there is widespread inflammation in the Alzheimer’s brain, it is not entirely surprising that an anti-inflammatory drug such as aspirin can help reduce the risk of AD. But to be effective, it has been shown that aspirin needs to be taken before the symptoms of Alzheimer’s disease set in. This is because aspirin has a preventive effect only, and once inflammation is widespread and the signs of the disease are apparent, it means that the brain is too damaged, many cells in the brain have already died, and it is therefore too late to begin any preventive approach.
There is also an interesting link between aspirin and the popular omega-3 fatty acid DHA. (which we offer in our Neurostrong. Think Smarter supplement) DHA is essential for the brain, and is reduced in Alzheimer’s desease. Because aspirin triggers DHA-derived factors that are neuroprotective, it has been suggested that the combined dietary intake of DHA and aspirin may help prevent and slow down Alzheimer’s disease.
We have looked in some detail at how aspirin may help prevent Alzheimer’s disease, but we thought the following links are also worth visiting if you are interested in learning about aspirin and colon and breast cancer prevention, both in the general population and in populations at risk.
If, after looking at the evidence, you are intrigued by the possibility of using aspirin on a regular basis for health reasons, always talk to your doctor first about it and decide together if it is appropriate for you. Your doctor is the best-qualified person to decide, based on your unique medical history, if the benefits of taking aspirin outweigh the risks of potential side effects.
And, as always, we will be happy to discuss any comments, questions or suggestions that you may have.
Posted in Alzheimer's Disease | Tagged Alzheimer's disease, aspirin, cancer, dementia, inflammation, NSAIDs, stroke |1 Comment
Understanding Schizophrenia
January 12, 2012Schizophrenia is unique amongst most brain disorders because of the social stigma that is attached to it, a stigma that leads to marginalization and a life exclusively defined by the condition. We don’t have the same negative associations with sufferers of Parkinson’s disease or Alzheimer’s disease for example. We understand that those conditions evolve from some molecular changes in the brain that need to be corrected, be it by medication and/or a variety of different therapies. That’s not the case with schizophrenia, which has an air of mystery associated with it that undoubtedly contributes to the idea that people who suffer it “are just crazy”. Ignorance is what drives the fear and rejection of schizophrenia, so the more we know about this difficult condition, the better we will be able to help those who suffer from it and their relatives and friends. The first thing to know is that schizophrenia is an illness like most others, in the sense that there is a biological reason for it and there is intensive research going on in pursuit of a cure or a treatment. Indeed, there are several clinical trials in place that are based on sound scientific findings and that offer some hope.
One interesting fact about schizophrenia is that it occurs at more or less the same rate across all cultures, which suggests that it may be inherent to the human condition and has led to scientist to search for “universal” theories explaining the origin of schizophrenia. Perhaps the most fascinating of those theories is related to the so-called Theory of Mind (ToM). The ToM refers to our ability to imagine the mental state of other people as well as ours. For example, we “assume” what someone else may be presently thinking, or infer what their beliefs are, or in general assess their behavior as if we were “in those people’s shoes”. The idea is that, by being able to continuously check people’s “intentions”, we are able to deal with complex social environments, where we interact with many people at many levels in many different situations.
Clearly, for this skill to be useful in society there have to be checks and balances within the brain to make sure that our inferences and assumptions about other people’s thoughts and intentions do not conflict with the signals from the environment that also reach the brain. In other words, we need to understand context in our social interactions, we need to sort out what matters from what doesn’t. And that’s where scientists think there might be a problem in the schizophrenic brain, the context is not accurately identified and taken into account, most likely because of the neuronal damage that pervades the schizophrenic brain in the relevant areas. The result is that objective and subjective thoughts can be one and the same, or at least they can overlap significantly, leading to delusional conclusions. An obvious consequence is a breakdown in communication with others, because of failure to identify their signals and intentions, and when that failure concerns the patient’s own signals, what occurs is the perception that foreign entities have taken over their minds (alien control). Obviously, not all patients suffer exactly the same symptoms all the time; the severity and scope of those symptoms will depend on what part of the ToM is more impaired, which in turn is probably a consequence of what exact area of the brain is more affected.
Some scientists think that the main cause of poor ToM abilities in schizophrenia sufferers is a breakdown of their communication and language skills. This is a very intuitive idea, because language is the main vehicle that we use to interact with others at the most complex levels, so perhaps part of the problem is that schizophrenia sufferers can’t use language tools as effectively. That could be the case, as it is not uncommon for them to take words and expressions literally, unaware of any context. For example, they can fail to recognize irony, a concept that is more complex than the plain use of words, or they may provide unclear or inadequate references in a conversation, which suggests lack of awareness regarding what may be required for a meaningful interaction.
As you can gather from all of the above, research on schizophrenia is moving along at several levels, all of which are important. Scientists are working on the molecular aspects of the disease, as well as on more abstract, but also testable, concepts, and the hope is that soon we’ll be able to blend all the information into a coherent body of knowledge that will help us cure, or at least contain, the disease. For those interested in learning more, please visit the schizophrenia research forum, a great site with access to the latest research on the disease as well as all sorts of support and learning resources.
Finally, remember that science alone is not enough in the fight against schizophrenia. We need better awareness of the disease in society, because perception matters and right now schizophrenia has an unacceptable stigma associated to it. Even today many patients can lead relatively normal lives if appropriately diagnosed, medicated and surrounded by their loved ones, so we can achieve a lot already by staying informed and participating at some level, perhaps even contributing a little; research is costly, and every little helps. If you are affected by schizophrenia at any level or want to learn more, click here to find support groups and related resources
Posted in Disease Center, Schizophrenia | Tagged language, schizophrenia, theory of mind |3 Comments
The facts about Alzheimer’s disease
January 10, 2012Alzheimer’s disease is the most common form of dementia. It can happen when mental health decline doesn’t stop at episodes of forgetfulness and generic lack of mental sharpness, but instead continues slowly into a full breakdown of brain function. We will be sharing with you regularly information that we hope will help not only sufferers of the disease, but also their families, caregivers and people concerned or interested in knowing more. For now, we want to direct your attention to the Alzheimer Research Forum, a great website committed to the understanding of Alzheimer’s disease and related conditions.
The site is thorough in its content and easy to navigate; if there’s anything that you want to know about Alzheimer’s disease or dementia, you are likely to find help here.
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