Richard G. Petty, MD

The Looming Crisis of Alzheimer’s

For those of us who lobby for resources, it is no overstatement to say that Alzheimer's disease has reached crisis proportions in the United States.

As we are getting older, the incidence, prevalence and mortality of Alzheimer’s disease are all rising.

The 2007 Alzheimer's Disease Facts and Figures report by the Alzheimer's Association makes sobering reading. Here are some of the headline facts:

• Alzheimer's disease is the most common cause of dementia
• At the present rate, one in 85 people will have the disease in 40 years
• There are now more than 5 million people suffering from Alzheimer's disease, and the report projects an increase of 16 million cases by 2050 unless preventive measures are taken and/or science is able to come up with a prevention or cure
• One person is now diagnosed with dementia every seven seconds
• One in every four American families is affected by dementia
• The incidence of dementia is one in 1,000 before age 65 and one in 20 after age 65.
• More than $100 billion is spent per year on dementia, which is about 10 percent of all healthcare expenditures

As we have discussed before, the symptoms of dementia may be delayed for 3 to 5 years through healthy lifestyles and behavior modification, and there are many new treatment approaches in the pipeline.

The huge issue is that statistic about one in four families being affected by the disease. And it is a disease: it is not part of normal aging.

Caregivers can suffer terribly.

The Alzheimer’s Association also has some information for those who care for people with Alzheimer’s.

There is also some food information here concerning caregiver stress.

I would also like to direct you to some of the things that I have written here about the wellness of caregivers.

And for everyone, don’t wait until you are thirsty before you dig that well. Work on building you personal resilience and follow the simple lifestyle guidelines that may significantly reduce your risk of developing Alzheimer’s disease.

More Clues to the Biology of Alzheimer’s Disease

Alzheimer’s disease remains a puzzle.

Although there are plenty of people who claim that “The Cause” of Alzheimer’s is… and here you can take your pick of three-dozen theories.

The truth of the matter is that simple explanations - Aluminum, lead, stress, pollution, mycoplasma infections and the rest – fail to explain many of the established observations about the causes of the disease.

From what we know about the genes in the brain, it is highly likely that “Alzheimer’s disease” represents a group of disorders that follow an interaction of sets of genetic and environmental factors.

This notion is supported by a report from investigators at Washington University School of Medicine, St. Louis and several other prominent research centers. The study is published in today’s issue of the journal Neuron and indicates that there a biological link between a protein mutation that causes early-onset Alzheimer's disease (AD) and a gene variant linked to late-onset AD.

The investigators tried to link the function of two known causative factors in AD. Mutations in amyloid precursor protein (APP) cause early-onset Alzheimer's disease (AD), but the only genetic risk factor for late-onset AD is the ɛ4 allele of apolipoprotein E (apoE), a major carrier of cholesterol in the circulation and in cell membranes.

Previous research has shown that mutations in APP can cause early-onset AD when the protein is “cleaved” or split, producing a short toxic protein that builds up in the brain and kills neurons. 

In their experiments with mice and cultured mouse cells, the researchers linked APP to the regulation of apoE and its cholesterol transport function. They found that the normal cleavage of APP in the cell gives rise to a nontoxic fragment (called AICD) that suppresses the gene that produces the cell receptor for apoE, known as LRP1. Crouching in nerve cell membranes, this receptor enables the apoE protein to transport its cholesterol cargo into the cell.

The researchers speculated that the loss of LRP1 function in AD might cause a loss of cholesterol that causes malfunction of neurons.

These observations may turn out to be extremely important. If we can restore the activity of the receptor gene, we might have a new treatment strategy for AD.

Protecting Yourself Against Alzheimer’s Disease

I have a keen interest in healthy aging, and we have talked before about some of the strategies that can help protect you against developing cognitive decline.

New research now shows for the first time that, of all lifelong activities, only a high level of mental or cognitive activity protects against the devastating memory loss of Alzheimer's disease. High levels of social or physical activity are not enough.

Researchers from the Byrd Alzheimer's Institute bred mice that are genetically predisposed to developing the pathological changes of Alzheimer’s diseases in their brains.

They then kept the mice in one of four housing environments -- high social activity, high physical activity, high cognitive activity, or a single housing control environment and watched them from young adulthood through old age.

When the researchers tested the mice in a battery of memory tasks in old age, only the mice given a lifelong high level of cognitive activity were protected against memory impairment. In fact, these "high cognitive activity" mice performed as well as normal mice that do not develop Alzheimer's disease. However the Alzheimer's mice raised in one of the other three environments performed poorly in multiple memory tasks.

Not only was memory protected in Alzheimer's mice by a high level of cognitive activity, but also brain levels of the abnormal protein beta-amyloid were substantially reduced. This protein, thought to be key for Alzheimer's development, remained at soaring levels in the brains of Alzheimer's mice raised in social or physical activity environments. Moreover, the researchers found that only the Alzheimer's mice raised with high cognitive activity had an increase in connections between brain cells. Alzheimer's mice raised in one of the other three housing environments had much fewer connections between their brain cells.

The new study is published in the Neurobiology of Learning and Memory Journal.

The lead researcher is Gary Arendash, and he had this to say:

“Our results call into question the earlier human studies suggesting social or physical activity provides protection against Alzheimer's. Alzheimer's begins in the brain several decades before any symptoms´ show up. That means adults in their forties and fifties need to make lifestyle choices now to decrease their risk of getting Alzheimer's disease later."

This is all correct, but there is still an important question: can we really extrapolate from mice to humans? Mice are social creatures, but not to the same extent as humans beings. The lion’s share of the human brain is dedicated to social activities, so you would expect that social activities will be particularly important in the maintenance of the human brain.

Alzheimer’s Disease: Diabetes of the Third Kind?

Insulin may have some extremely important roles in the mind as well as the body.

Though best known for its role in promoting glucose uptake into cells, insulin has at least five hundred known functions in the human body. For many years nobody was sure whether insulin was important to the brain: neurons in the brain are unusual in that they do not need insulin to enter them. But then we discovered that insulin acts on other important metabolic processes in neurons. In the brain it also does duty as a chemical messenger and as a growth factor, and brain insulin signaling is crucial for the creation of memory. Over the years a number of theorists have suggested that some neurological and psychiatric illnesses could be a result of disturbances in insulin-related processes in the brain.

It is now beginning to look as if they may have been correct.

Some recent evidence has suggested that Alzheimer’s disease and diabetes mellitus share a number of common pathways and Alzheimer’s disease is associated with peripheral insulin resistance.

New research has been published by investigators from Northwestern University in the FASEB Journal - the journal of the Federation of American Societies for Experimental Biology –  that may finally nail down the reason why insulin signaling may stop working in Alzheimer’s disease.

The research team used mature cultures of neurons from the hippocampus of the brain to study synapses – the connection between neurons - that have been implicated in learning and memory mechanisms. They wanted to examine the effect of a toxic protein, known to attack memory-forming synapses, that is called  “ADDL” for "amyloid ß-derived diffusible ligand." ADDLS are small, soluble aggregated proteins that accumulate in the earliest stages of Alzheimer’s disease. The researchers had previously found that ADDLs bind very specifically at synapses, which in turn initiates deterioration of their function, shape and composition. They now went on and studied the synapses and their insulin receptors before and after ADDLs were introduced. Regions of the nerve with normal numbers of insulin receptors have no ADDL binding, but when the ADDLs are added they remove insulin receptors from nerve cells, effectively making them insulin resistant.

And an insulin resistant neuron cannot participate in the formation of memories.

This finding implies that there is a fundamental connection between diabetes and Alzheimer's disease, and this may in turn help us to see whether existing diabetes treatments might protect neurons from ADDLs and improve insulin signaling in people with Alzheimer's disease.

The first type of diabetes is Type 1, a.k.a. insulin-dependent or juvenile onset. The second is Type 2, a.k.a. non-insulin-dependent diabetes. So is Alzheimer's Type 3?

It has also been known for some time that physical exercise is one of the factors that may help reduce the chance of developing Alzheimer’s disease, and we may now have a mechanism by which it can help.

This is an extraordinarily interesting and important discovery that should lead to a whole new research angle, perhaps with medicines that are already available.

Glaucoma and Alzheimer’s Disease

There is a fascinating study by colleagues from University College London (UCL) that has just been published in the Proceedings of the National Academy of Sciences that has found a "clear link between what causes Alzheimer's and one of the basic mechanisms behind glaucoma.”



The research could speed up the development of new treatments for Alzheimer's and revolutionize the treatment of glaucoma, the most common cause of blindness in the Western world.

If glaucoma is indeed confirmed as a marker or risk factor for Alzheimer's then the early warning signs it gives could help ensure that patients have more opportunities to delay the onset of dementia.

The researchers discovered that the same "plaque" proteins are a key process in the development of both diseases. Clumps - or plaques - of beta-amyloid proteins that  kill brain cells in Alzheimer's patients, also kill optic nerve cells in the eyes of glaucoma sufferers. A link has bee suspected for some time: around 1.8-2.0% of the population will develop glaucoma, the figures in Alzheimer’s is as high as 25%.

Dr Francesca Cordeiro, who led the team at UCL's Institute of Ophthalmology, said:

“We've seen for the first time that there is a clear link between what causes Alzheimer's and one of the basic mechanisms behind glaucoma."

Glaucoma is a group of diseases of the optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. People with glaucoma gradually lose their wider field of vision. Many do not realize it until they barge into things.

The textbooks will tell you that glaucoma is caused by increased pressure in the eye, known as intraocular pressure. Standard treatments attempt to lower this pressure, but with only limited success. People with normal pressure can also suffer from glaucoma, suggesting it is not the only cause.

The researchers have shown that drugs that prevent the build-up of "plaque" proteins in the brains of people with Alzheimer's disease were successful in treating glaucoma in rats. One such drug, bapineuzumab, is already being used to treat Alzheimer's patients in clinical trials in Britain and the United States.

The UCL researchers showed that the effects on glaucoma were even stronger when combined with two other novel Alzheimer's treatments - "Congo Red" and a drug called a beta-secretase inhibitor.

This is very exciting work and we should know fairly soon whether these new approaches to treatment will help both glaucoma and Alzheimer’s disease.

Clearly this does not mean that everyone with Alzheimer's will develop glaucoma or vice versa. Both problems have multiple causes and can follow quite different trajectories. But links like these are the stuff of medical progress.

Insulin Resistance and Cognition

I have talked a lot about insulin resistance and the problems that it can cause. It is one of the biggest threats facing the human population, with at least a third of Americans now being insulin resistant. It looks as there may be another complication of insulin resistance that we need to add to the list.

Researchers from Canada presented some interesting data (NR385) at the 2007 Annual Meeting of the American Psychiatric Association in San Diego last month.

There has been a great deal of concern that some newer antipsychotics may cause insulin resistance and perhaps diabetes, and the FDA has required all the newer antipsychotics to carry a warning about this potential problem. We also know that although these medicines can be very effective in treating some symptoms, they do not usually help cognition very much.

The researchers recruited 37 people with chronic schizophrenia and did neurocognitive tests on them while also measuring their insulin resistance.

They found a significant correlation between insulin resistance and neurocognitive functioning. It looks as if insulin signaling is important for processing information in the brain and insulin resistance interferes with the process.

Though this study look at a highly specialized group: people with chronic schizophrenia – there is some recent evidence to suggest that insulin resistance may be a factor in Alzheimer’s disease, and that people may develop cognitive impairments if they go on to develop insulin resistance syndrome or impaired fasting glucose.

Yet another good reason for using diet, exercise and sleep to try and present insulin resistance and maintain healthy glucose levels.

Regular readers will recall that there are five pillars of healthy aging and the prevention of cognitive decline:

1. Blood pressure
2. Physical activity
3. Mental activity
4. Supplements and moderate alcohol
5. Social engagement and level mood

We should now add avoidance of insulin resistance to the list. Taken together, the evidence suggests that we can dramatically reduce our risk of cognitive decline as we get older.

Personal Mastery and the Wellness of Caregivers

Looking after aging relatives can be incredibly difficult, particularly if they have a chronic illness such as Alzheimer’s disease.

There is also evidence that the caregivers of people with Alzheimer’s disease have increased rates of cardiovascular disease and they die prematurely. It has been assumed that the cardiovascular problems are a result of stress causing overdrive of the sympathetic nervous system.

There was some interesting research (NR241) presented last month at the 2007 Annual Meeting of the American Psychiatric Association in San Diego. The investigators did not have to come far: they are from the University of California in San Diego.

The investigators looked at 70 spousal caregivers of people with Alzheimer’s disease and used an experimental task to measure the activity of their sympathetic nervous systems. They also measured the caregiver’s levels of “Mastery:” the belief that one is capable of handing one’s problems. Mastery is one of the components of resilience, a key characteristic of a person who can handle stress well.

What they found make very good sense: the caregivers with the highest levels of personal mastery had the lowest levels of sympathetic activity, suggesting that a sense of mastery may protect against the physiological effects of acute stress.

This provides us with yet more evidence that psychosocial interventions that increase mastery may reduce the risk of cardiovascular disease amongst the caregivers of people with dementia.

Successful Aging

One of the most promising changes in psychology is the ever-greater emphasis on what makes us healthy, rather than constantly looking at the things that make us sick. There is an important approach called Behavioral Activation (BA) Theory, which emphasizes environmental and behavioral factors as determinants of our overall well-being. According to the theory, reduced engagement in pleasurable activities may be an important precursor of reduced well-being. This makes good sense: it is estimated that as much as 90% of our higher cortical functions are designed for social interactions.

This is something that I wrote in Healing, Meaning and Purpose:

"Nothing in the Universe exists in isolation: We live in a Universe of relationships. It is inconceivable that anything can exist except in relationship to something else. The entire Universe is made up of integrated systems that function, develop and evolve together. A failure to construct and maintain healthy relationships can be a cause of much distress.

Several years ago I reported some interesting observations. At the time, I was doing a lot of research on diseases of blood vessels. I had developed a laboratory method for taking some of the cells that line blood vessels from volunteers and then growing them in a cell culture dish. We discovered that if we did not have enough cells in the dish, they would all die of “loneliness.” The exception is cancer cells, which in culture will grow on their own, like weeds."

As an example in a paper published in February in the Archives of General Psychiatry it was shown that lonely individuals may be twice as likely to develop the type of dementia linked to Alzheimer's disease in late life as those who are not lonely. The theory has been shown to predict psychiatric well-being in a number of populations, including the caregivers of people with Alzheimer’s disease, people with chronic pain, cancer patients and community-dwelling older people.

It is also known that psychiatric well-being, particularly emotional well-being, may play an important role in cardiovascular health. This may be due to an increase in the activity of the sympathetic nervous system that increases not only blood pressure, but also the levels of inflammatory mediators and coagulant factors in the blood.

In research from the University of California at La Jolla that was presented on Monday at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California, twenty two people with a mean age of 70 were studied, to see if there was a link between their behavioral activation, i.e. how satisfied they were with their leisure activities, their affective well-being and their blood pressure.

The findings were as expected: the less satisfied and engaged people were, the higher was their blood pressure.

This is only preliminary data, but it confirms something that we have said before: as we get older it is as important to stay socially engaged as it is to do mental exercise.

And if you known someone who is older and isolated, you might want to go and see them.

“The most terrible poverty is loneliness and the feeling of being unloved.”
--Mother Teresa of Calcutta (Albanian-born Indian Nun, Humanitarian and, in 1979, Winner of the Nobel Peace Prize, 1910-1997)

“What makes loneliness an anguish is not that I have no one to share my burden, but this: I have only my own burden to bear.”
--Dag Hammarskjöld (Swedish Statesman, Secretary-General of the United Nations from 1953-1961, and, in 1961, Winner of the Nobel Peace Prize, 1905-1961)

Attachment and Well-Being In the Elderly

Attachment theory is a psychological concept that was developed by John Bowlby in Britain and Harry Harlow in the United States in the late 1950s. The idea is that humans and many other animals have evolved an adaptive tendency to maintain proximity to an attachment figure.

Attachment is defined as an emotional bond that one person forms between himself or herself and another specific person. Originally the theory was developed to explain the relationship of a parent and child, but over tie it has become realized that attachments can occur throughout life, and if they become abnormal, they can lead to loneliness, isolation and psychopathology. There has recently been a resurgence of interest in attachment styles, and how they interact with emotional and behavioral expression during the development of dementia.

There was some interesting research presented today at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California. Investigators from Charlottesville, Virginia looked at 39 older patients (27 were women): 49% were aged between 65 and 74 and the remainder was over 74.

• 41% of women and 33% of the men said that their activities were limited by physical and/or emotional problems
• 41% of the women and 17% of the men endorsed at least two out of three indicators of depression
• When they examined their attachment styles, 28% were secure, 59% avoidant and 13% enmeshed
• An avoidant attachment pattern is more common among the elderly than it is among younger people
• Understanding attachment style could be very helpful in understanding how people react to their healthcare providers and their preferred coping styles

For anyone working or living with elderly people, attachment theory is well worth investigating. There is already some preliminary evidence that specific interventions may help older people with avoidant attachments.

Attachment theory is a psychological concept that was developed by John Bowlby in Britain and Harry Harlow in the United States in the late 1950s. The idea is that humans and many other animals have evolved an adaptive tendency to maintain proximity to an attachment figure.

Attachment is defined as an emotional bond that one person forms between himself or herself and another specific person. Originally the theory was developed to explain the relationship of a parent and child, but over tie it has become realized that attachments can occur throughout life, and if they become abnormal, they can lead to loneliness, isolation and psychopathology. There has recently been a resurgence of interest in attachment styles, and how they interact with emotional and behavioral expression during the development of dementia.

There was some interesting research presented today at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California. Investigators from Charlottesville, Virginia looked at 39 older patients (27 were women): 49% were aged between 65 and 74 and the remainder was over 74.

• 41% of women and 33% of the men said that their activities were limited by physical and/or emotional problems
• 41% of the women and 17% of the men endorsed at least two out of three indicators of depression
• When they examined their attachment styles, 28% were secure, 59% avoidant and 13% enmeshed
• An avoidant attachment pattern is more common among the elderly than it is among younger people
• Understanding attachment style could be very helpful in understanding how people react to their healthcare providers and their preferred coping styles

For anyone working or living with elderly people, attachment theory is well worth investigating. There is already some preliminary evidence that specific interventions may help older people with avoidant attachments.

Alzheimer’s: “A Disease of Civilization?”

I have had the pleasure of receiving some excellent comments after the recent article about Alzheimer’s disease.

One suggestion was that Alzheimer’s is a modern illness caused by mercury in dental fillings. This has been a popular idea for several years, and I knew an holistic dentist in Philadelphia who told me about some people who seemed to be relieved of an array of symptoms after their mercury-containing fillings were removed.

Over the last few years I have spent a long time reading books on the topics and analyzing published studies in detail.

These are some of the books with which I started:

1. Warren T. Beating Alzheimer's: A Step Towards Unlocking the Mysteries of Brain Diseases. Garden City Park, New York: Avery Publishing Group Inc., 1991.
2. Huggins HA. It's All in Your Head: The Link Between Mercury Amalgams and Illness. Garden City Park, New York: Avery Publishing Group Inc., 1993.
3. Walker M, Whitaker J. Elements of Danger: Protect Yourself Against the Hazards of Modern Dentistry. Charlottesville, Virginia: Hampton Roads Publishing Company Inc., 2000.
4. Hardy JE. Mercury Free: The Wisdom Behind the Global Consumer Movement to Ban "Silver" Dental Fillings Glassboro, New Jersey: Gabriel Rose Press Inc., 1996.

One of the best resources that I’ve found for people interested in the potential problems that may be caused by dental amalgams is here.

Clearly there is a potential for harm. At one time I considered having my fillings removed, but in the end I didn’t.

Why did I make that decision?

After all, mercury is neurotoxic, which is one of the reasons for all the concern about thimerosal in vaccines, and its alleged link to autism. And I would prefer to avoid getting Alzheimer’s disease. I have no family history of it. In fact the opposite: my father was estimated to have an IQ in the 170-180 range when he was in his nineties. But it is still a concern.

While some people seem to have benefited form having their fillings removed, many have not. So there must be some other factor or factors, likely including a genetic predisposition. People have created genetically deformed animals with all the signs of Alzheimer’s disease, but without a molecule of mercury in sight.

It is constantly being said that Alzheimer’s disease is a modern illness, and that its appearance roughly coincided with the introduction of mercury fillings. But that’s not true. Alois Alzheimer did describe the classic pathological signs of the disease in 1906. It was only made possible by the development of a new silver staining method developed by Alzheimer’s colleague Franz Nissl. For the first 70 years after it was first described, Alzheimer’s disease was regarded as a “Pre-senile” dementia.

But dementia had been described at least two thousand years earlier by Lucretius.

Some of those early descriptions probably included a ragbag of different illnesses, but for at least 2,000 years, from Rome to China, there were clear descriptions of something that looks just like modern Alzheimer’s disease. There are descriptions by the great English physician Thomas Willis, and the term “demented” entered the English language in 1644. There was a famous description of Sir John Roberts of Bromley, who was described by his physician, William Salmon as “decayed in his intellectuals.” That was in 1694.

There are extensive descriptions of “senile dementia” from many of the famous names in the history of psychiatry, including Cullen, Pinel and Esquirol. So the idea that it is a modern illness is not correct. Has it been becoming more common? Possibly, but it is difficult to say, because in 1905 the average life expectancy in the United States was 47 years.

When I really started analyzing the research in detail, I was not impressed by the data linking mercury with Alzheimer’s disease and multiple sclerosis. There are definitely some reports (1.2.) of possible links between neurodegeneration and mercury, but the most recent epidemiological studies have failed to find a link. Indeed there has been a great deal of research indicating that – for most people – amalgams are safe. ( 1. 2. 3. 4.) although it is important that the research should continue. Last year the U.S. Food and Drug Administration (FDA) panel called for an additional review of scientific studies on the safety of dental amalgam fillings. Some of the responses are here.

My own take on this is as follows:

1. The evidence for a causal link between mercury – primarily from fillings – and Alzheimer’s disease is thin.
2. The quality of the evidence for many other conditions, such as multiple sclerosis is also not of good quality.
3. There is still a great deal that we do not know about the medical consequences of mercury containing amalgams, particularly in children and pregnant women.
4. I am going to continue to update this information as more data is published.

At the moment I still have my fillings.

But there is another reason: the few that I have were done in England, and for years now there have been restrictions on the use of mercury-containing amalgams.

Linking Depression, Diabetes and Alzheimer’s Disease

It has been known for many years that Alzheimer's disease and depression are associated with type 2 diabetes. Good control of blood glucose may reduce the risk of developing Alzheimer’s disease and depression, while treating depression may improve metabolic control.

Decreased levels of brain-derived neurotrophic factor (BDNF) have also been implicated in the pathogenesis of Alzheimer's disease and depression, and animal models have suggested that BDNF may play a role in insulin resistance.

So a group of scientists at The Centre of Inflammation and Metabolism, Department of Infectious Diseases at the University of Copenhagen in Denmark, decided to see whether BDNF plays a role in human glucose metabolism.

In the first study they looked at 233 people and found that BDNF was inversely associated with fasting plasma glucose, but not with insulin. In a second smaller study they did what are known as hyperglycemic and a hyperinsulinemic-euglycemic clamp studies, that allowed them to look at the relationships between BDNF, glucose and insulin. What they found was that output of BDNF from the brain was inhibited when blood glucose levels were elevated.

So it seems that low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a factor involved not only in dementia and depression, but also in type 2 diabetes, and it may be the missing link that explains the way in which the three conditions cluster together in epidemiological studies

This link between a chemical produced in the brain and diabetes is not altogether unexpected. The French physiologist Claude Bernard demonstrated that stimulation of the fourth ventricle of the brain caused glucose to rise, and it was later found that opiates put into this region of the brain could do the same thing.

This study reinforced the close links between metabolism and the brain, and gives us another reason for recommending that as we get older we must ensure that out glucose remains stable and that we do not become depressed.

Insulin Resistance in the Brain and What It Means for Dieters

Most people have been taught that increasing weight is the cause of insulin resistance, which in turn may cause an array of different health problems. That is only half true: insulin resistance may contribute to the development of obesity, and once we start gaining abdominal fat then that may indeed contribute to insulin resistance. So a vicious circle is established in which insulin resistance helps cause obesity, which in turn causes more insulin resistance.

Another thing that we have been taught for half a century that the brain is an insulin-insensitive tissue. What that means is that the uptake and use of glucose by the brain is not affected by circulating levels of glucose and insulin. That has always seemed a bit strange, because insulin is very important in cognition. Some experts believe that disturbances of insulin and closely related hormone – insulin like growth factor 1 (IGF-1) are involved in the pathogenesis of Alzheimer’s disease. 

When someone is insulin resistant, they have high circulating levels of insulin, and an obvious question is whether these high insulin levels may interfere with the normal functions of the brain. This is not a new idea. It has been known for many years that high levels of triglycerides, that may be a marker for insulin resistance, may be associated with cognitive impairment in people with type 2 diabetes.

Now colleagues in London have found that people who have peripheral insulin resistance also have brain insulin resistance especially in two brain regions  - the ventral striatum and prefrontal cortex – that are involved in appetite and reward.

It looks as if one of the reasons why people with insulin resistance become obese is that the normal link between the control of food intake and energy balance is broken.

This is yet more evidence that a simple diet will not work in the long term. If the problem is metabolic and involves damage to the mechanisms that control eating, the only way to help is to use a combined approach that deals not only with the composition of the diet, but the precise time when people should eat, and the psychological and social barriers that are left over from millions of years of evolution. I outline a comprehensive and highly successful weight management technique in Healing, Meaning and Purpose. Over the last few months I have had an enormous number of requests to expand that material into another book, and in between writing this blog, I am hard at work on completing a full account of exactly what we do to help people manage their weight.

Lithium and Brain Growth

There’s an interesting story about the way that lithium was found to be helpful to some people with bipolar disorder. It was thought that there was a link between bipolar disorder and gout, and gout is caused by an accumulation of uric acid in some joints. It just so happens that lithium is very good at getting guinea pigs to pass any excess uric acid in their urine. So in 1949 a medical scientist in Australia called John Cade tried lithium in bipolar disorder. It worked, but not because of any effect on uric acid: the lithium/uric acid connection only works in guinea pigs. But now, all these years later, it turns out that there may actually be a link between bipolar disorder and uric acid after all: uric acid levels often rise in people who are insulin resistant, and insulin resistance is a common feature of bipolar disorder.

The last few years have seen the growth of an impressive body of evidence about the effects of lithium on the brain.  Lithium modulates the way in which many neurotransmitters act in the brain. That raised interesting questions, because many of the chemical transmitters do not only send messages between neurons, they may also stimulate the growth of cell processes and perhaps neurons themselves. Then it was discovered that lithium protects neurons by increasing the levels of a neuroprotective protein called Bcl-2. Then it was found to help stimulate the production of new neurons (neurogenesis) in the hippocampus.

A major breakthrough came in 2000, with the demonstration that lithium increases the amount of gray matter in the human brain, probably by stimulating the production of a growth promoter called brain-derived neurotrophic factor. Gray matter is composed primarily of neurons, so this suggested that lithium was either stimulating the growth of new neurons, or causing the migration of neural stem cells, or alternatively somehow preventing the death of neurons.

Within less than two years it was confirmed that treatment with lithium increased the amount of gray matter in the brains of people with bipolar disorder.

The findings remained controversial for two reasons: first was the seeming impossibility of stimulating the production of new gray matter. That is no longer such a problem: there is more and more evidence that the adult brain can indeed produce new neurons. The second problem was technology: the measurements were open to different interpretations.

Now neuroscientists at UCLA, using brain scans collected by collaborators at the University of Pittsburgh School of Medicine have shown that lithium does indeed increase the amount of gray matter in the brains of patients with bipolar disorder. But what is far more important is that the effects are seen in precise regions of the brain that are thought to be implicated in bipolar disorder.

The research is published in the July issue of the journal Biological Psychiatry.

Carrie Bearden, a clinical neuropsychologist and assistant professor of psychiatry at UCLA, and Paul Thompson, who is associate professor of neurology at the UCLA Laboratory of NeuroImaging, used a novel method of three-dimensional magnetic resonance imaging (MRI) to map the entire surface of the brain in people diagnosed with bipolar disorder. Everyone interested in the brain has been amazed by the quality of the images coming from the UCLA lab over the last six or seven years. (Graphics from the study, including the one above, are available online here.)

When the researchers compared the brains of bipolar patients on lithium with those of people without the disorder and those of bipolar patients not on lithium, they found that the volume of gray matter in the brains of those on lithium was as much as 15 percent higher in the cingulate and paralimbic regions of the brain, that are critical for attention, motivation and emotional control. There was no change in the amount of white matter, telling us that these effects are unlikely to be either artifacts or swelling of the brain.

These are extraordinary findings that may help explain how lithium works. If lithium increases the amount of gray matter in specific regions of the brain, this may suggest that existing gray matter in these regions may be underused or dysfunctional in people with bipolar disorder.

Conventional MRI studies in bipolar disorder measured the total volume of the brain, but these new imaging techniques employ high-resolution MRI and cortical pattern-matching methods to map gray matter differences that are so precise that they can pick up subtle differences in brain structure and this is the first time that researchers have been able to look at specific regions of the brain in people with bipolar disorder, and examine the effects of treatment.

The researchers at UCLA analyzed MRI scans of 28 adults with bipolar disorder, 20 of whom were lithium-treated, and 28 healthy control subjects collected by collaborators at the University of Pittsburgh. The analysis involved detailed spatial analyses of the distribution of gray matter by measuring local volumes of gray matter at thousands of locations in the brain.

This is superb research, and one of the signs of good research is that it raises yet more questions:

• We do not know whether these effects on gray matter persist once the medicine is stopped.
• Neither do we know whether the same effect might occur in other illnesses in which there is loss of gray matter. It may just be that lithium corrects an abnormality that is specific to bipolar disorder. That being said, there is recent evidence that lithium may be neuroprotective in a mouse model of Alzheimer’s disease.
• We also do not know if these brain changes correlate with clinical improvement.
• Lithium can have a lot of side effects, so we shall also need to factor that into the equation.
• We also need to know whether other medicines - or any other kind of therapy - might produce similar effects: there are already several medicines that have been shown to do something similar in some animals.

It's still a bit too early to suggest putting lithium in the water supply...

A Major Breakthrough in Neurogenesis Research

I have written a lot about adult neurogenesis, because it is so incredibly important.

When most of us were in school were taught that the brain is a static structure. That you are born with a certain number of neurons, that constitutes your neural “stash.” And after the age of five you would lose a hundred thousand neurons a day, and if you drank too many martinis it would be two hundred thousand a day. “Facts” and figures repeated from one textbook to another for fifty years. And quite wrong.

Ten years ago it was discovered that there are neural stem cells in the hippocampi of adult rodents. A study published in 1998 provided some evidence that neurogenesis takes place in the adult human hippocampus, but the idea that neurogenesis takes place in adult humans has remained contentious.

Now, an advance online publication on the website of the journal Science provides evidence that neurogenesis may also occur in the olfactory bulb of the human brain.

The whole article, including the pictures is available here. The picture at the top of this article shows new cells appearing in the olfactor bulb.

The investigators examined the rostral migratory stream (RMS) which is the main pathway by which newly born cells from the subventricular zone (SVZ) reach the olfactory bulb in rodents. The researchers discovered that there is a human RMS containing neuroblasts, a.k.a. neural stem cells.

(This is a rat olfactory bulb)

Maurice Curtis and his colleagues examined the brains of cancer patients who had recently died, after having been previously injected with bromodeoxyuridine (BrdU), a chemical that is incorporated into newly synthesized DNA. Cell biologists and oncologists have used the method for years to visualize and monitor the growth of tumors. The researchers found BrdU-positive cells in the olfactory bulbs of the patients’ brains, indicating that they contained newly-generated neurons.

The team then used antibody staining to show that the neuroblasts begin to differentiate into olfactory neurons while migrating through the rostral migratory stream. Upon arriving at the bulb, the cells continued to differentiate, forming mature olfactory neurons.

The patients whose brains were examined were between 38-70 years of age, so the findings show that neurogenesis may occur throughout the duration of the human lifespan. The function of these newly generated cells is unclear, but they may be involved in recognizing and remembering new smells in the later years of life.

The researchers also have preliminary unpublished data that the stem cells not only migrate to the olfactory bulb, but also leave the RMS and migrate into the basal ganglia and cerebral cortex. This is significant, because parts of the basal ganglia degenerate in movement disorders such as Parkinson’s Disease, and specific regions of the cortex degenerate in Alzheimer’s. The possibility that stem cells enter these regions from the RMS could therefore provide a means for developing new treatments for neurodegenerative diseases.

So although at the moment new neurons are only known to be created in a small number of ancient structures in the brain, but that may well change, since the cells are marching over there from regions around the ventricles. After all, why would Nature, the Universe or God have left neural stem cells sitting there unless it was for a good reason? And if adult neurogenesis can be demonstrated in other parts of the brain, then what? An end to the stem cell debates? If the stem cells are already present in the brain, the effort can be directed toward activating and directing them. Could we continue generating new neurons to stave off the dementing illnesses, or is that just science fiction?

The answer is that science fiction is fast becoming science fact. This research will need to be replicated, but I know of several other labs that have already accumulated some similar data to this new paper in Science.

Juices, Cardiovascular Disease and Cancer

There was an important study that came out a few months ago in the International Journal of Food Science and Nutrition.

Investigators from Dundee in Scotland decided to look at the health benefits of fresh fruit juice. While it is widely accepted that fruit and vegetables lower the risk of some cancers and of most cardiovascular diseases, the role of pure fruit and vegetable juices has never been clear. In fact many textbooks have said that 100 percent juices play a less significant role in reducing risk for both cancer and cardiovascular disease than whole fruits and vegetables since they contain less fiber, and it had been assumed that it was the fiber that was the key to their value.

The researchers analyzed a variety of studies that looked at risk reduction attributed to the effects of both fiber and antioxidants. They found that the positive impact offered by fruits and vegetables is derived not from just the fiber but also from antioxidants which are present in both juice and the whole fruit and vegetables. Juices are comparable in their ability to reduce cancer and cardiovascular risk compared to their whole fruit/vegetable counterparts.

This research  goes a long way in demonstrating that fruit and vegetable juices may play an important role in reducing the risk of various diseases.

A study published in the American Journal of Medicine in September found that consuming a variety of 100 percent fruit and vegetable juices was associated with a reduced risk for Alzheimer's disease. Japanese American individuals who drank three or more servings of fruit and vegetable juices per week had a 76 percent lower risk of developing Alzheimer's disease than those who drank juice less than once per week. That finding seemed robust, even taking into account other potential variables. So I think that we may be able to add juices to our strategies for reducing the risk of developing Alzheimer's disease as we get older.

There is another point of importance. Some of the fad diets claim that fruit juices should be avoided at all costs, since they can cause the release of insulin, and insulin is bad. Those proclamations have usually come from people with a limited background in biochemistry or metabolism. The research shows that they were not correct. The key is balance, and as part of a comprehensive nutritional approach, juicing can be very helpful.

And a final point: careful use of juices has long been one of the "secret" components of our system of weight management.

“Drinking freshly made juices and eating enough whole foods to provide adequate fiber is a sensible approach to a healthful diet.”
--Jay Kordich (American Health Expert, Author and Lecturer, 1921-)

“If people would only stop putting into their bodies the things that are creating their physical problems, and eat a predominantly raw vegetarian diet, along with raw vegetable juices, almost all physical problems would soon disappear from the face of the earth!”
--Reverend George M. Malkmus
 (American Minister and Originator of the Hallelujah Diet, 1934-)

Leg Length and Cognitive Reserve

I recently mentioned the "Barker Hypothesis" which says that fetal malnutrition is associated with many physical problems later in life.

Well the difficulties may not only be physical.

I would like to tell you about an important concept that we call "Cognitive reserve." This can be thought of as our cognitive resilience. This first came to light almost twenty years ago when a post-mortem study of 137 elderly people was published in the Annals of Neurology, and confirmed something that we had suspected for years: there was a large discrepancy between the degree of Alzheimer’s disease neuropathology and the clinical manifestations of the disease. Some people had extensive pathology but they  clinically had no or very little manifestations of the disease. The investigators also showed that these people had higher brain weights and greater number of neurons compared with age-matched controls. This lead to the idea that they had a greater "reserve." This is why building your brain throughout life is thought to reduce the ce of cognitive impaitrment later on.

Studies have shown that childhood cognition, educational attainment and adult occupation all independently contribute to cognitive reserve, and more recently it has been confirmed that education and the complexity of a person's occupation may both slow the rate of decline in people who already have Alzheimer's disease.

Although height is in part genetically determined, shorter leg length has been found to be associated with an adverse environment in early childhood. In a recent study of older Afro-Caribbean people living in London, shorter leg length was significantly associated with cognitive impairment, leading to the suggestion that shorter leg length may be a marker of early life stressors that then result in reduced cognitive reserve.

It is also worth recalling our discussion about the association between growth hormone and intelligence in children and between intelligence and head size.

And nutrition is one of the determinants of growth hormone synthesis and release.

Naturally this does not mean that less tall people will all get Alzheimer's disease. But these observations have a number of practical consequences. They re-emphasize the importance of good nutrition during pregnancy: something that is simply not available to over a third of the world's population. They also help us to identify some of the people who would most benefit from strategies to increase their cognitive reserve and to avoid some of the things that can strip it away from them.

Healthy Aging

I have talked about the small number of simple steps that can dramatically reduce your risk of getting congnitive decline as your get older and some new evidence to show the benefits of non-drug treatments for dementia. I am pleased to say that my conclusions have just been supported by an editorial in the Journal of the American Medical Association.

I would like to let you know about another great resource: the International Council on Active Aging (ICAA) which has produced a great package of action items that are all rooted in good quality scientific research. The list is very similar to the ones that I have created for you here, and are very precise.

1. Invest in good shoes and socks
2. Play games
3. Walk
4. Increases your physical activity
5. Do exercises to improve your balance
6. Get regular eye checks, not only for corrective lenses, but to be checked for early evidence of diabetes or high blood pressure
7. Seek out friends family and neighbors
8. Modify your diet toward a "Mediterranean" one
9. Laugh
10. Get enought sleep

Whatever your age, I urge you to spend a few minutes working on a simple plan that will fit your schedule: your mind and body, family and friends will thank you forever.

Parkinson's Disease and Cholesterol

Within the last week we have talked about the association between Helicobacter pylori and Parkinson's disease and the way in which Parkinson's disease may often get better if people are treated with a cocktail of antibiotics. We have also discussed the association between Parkinson's disease, allergies and inflammation.

Now new research from the University of North Carolina at Chapel Hill has  found that people with low levels of LDL cholesterol are more likely to have Parkinson's disease than people with high LDL levels. This is the form of cholesterol sometimes referred to as "bad cholesterol." This study followed the strange observation that people with Parkinson's disease have a lower rates of heart attack and stroke than people who do not have the disease. It is also known that known that cigarette smoking, which increases a person's risk for cardiovascular disease, is also associated with a decreased risk of Parkinson's disease. 

Few scientific stories are clear cut: it usually takes a while to get things right. Just to prove it, a study from the Netherlands found that high total cholesterol levels were associated with lower rates of Parkinson's disease, but only in women.

So what to make of all this: infections, allergies and now cholesterol?

To try and understand this, I think that we need to introduce another actor to the stage. Since the early 1950s the medical community has been concerned about a striking concentration of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia among the Chamorro people on the island of Guam. A number of lines of evidence have suggested that this group of illnesses has been caused by some neurotoxic agent in the environment, though nobody has been able to work out exactly what it is. One of the most attractive recent theories is that it might have something to do with toxins from Cycas plants. So the idea is that similar cholesterol-containing neurotoxins can come either from Helicobacter or from eating Cycas plants, or animals that have fed on the plants.

There is a complex inter-relationship between LDL- and HDL-cholesterol, and HDL-cholesterol appears to be anti-inflammatory: high levels of HDL-cholesterol are associated with low levels of inflammation. And it has recently been shown that simvastatin may cut the risk of developing Parkinson's and Alzheimer's diseases. Not just by lowering cholesterol but from its inflammatory activity.

It may also be that low levels of cholesterol may impair the activity of another factor: one that interests me is coenzyme Q10.

From a practical perspective, this new evidence reinforces a point that I made in Healing, Meaning and Purpose and on this blog: "boosting" one component of the blood or lowering another is not sensible. Whether dealing with cholecterol or immunity, we need to moduate and harmonize all the systems of our bodies and our minds.

Follow our systems for modulating the inflammatory mediators in your body and that alone should - theoretically - reduce your risk of many illnesses.

I shall keep you posted as this story continues to develop.

Learning to Tango

As a youngster I was introduced to most of the social graces: piano lessons – which sadly I hated – shooting, horse riding, fencing and ballroom dancing. And I just loved to tango!

Now I learn that it is, perhaps, something that more people should try.

Colleagues from the University of Turin used functional magnetic resonance imaging to study the hypothesis that simply focusing attention on walking could modify the activity of specific regions of the brain. But instead of using regular walking they taught people to tango. (The whole paper is available online as a free download.)

If you think about it for a moment, regular walking is an automatic process that you learned as a small child. It involves a series of structure in the deep – subcortical - regions of the brain and the spinal cord. The researchers got their experimental subjects to learn the dance by a combination of physical and mental practice. They were asked to perform the basic steps of the tango followed by imagining that – without moving - they were doing the steps.

The experiment showed that the training was associated with an expansion of regions of the brain involved in imagining movement. After the training the visual imagery gradually gave way to motor and kinesthetic ones.

This makes good sense: we normally begin by visualizing and then over time a motor skill like this becomes automatic. I’ve known good dancers who could flip from one dance to another without a moment’s thought.

This new finding suggests that rehabilitation of people who have lost the ability to walk should involve not just the motor act of walking, but also visualization.

But notice that the two processes – visualization and motor learning are separate. This is another nail in the coffin of the popular idea that your brain cannot tell the difference between a real and an imagined activity.

It also provides further evidence that both mental and physical activities can expand and activate regions of the brain.

And what a fun way to do it!


“The truest expression of a people is in its dance and in its music. Bodies never lie.”
--Agnes de Mille (American Choreographer, 1905-1993)

Brain Gain

We have previously discussed how a relatively small number of strategies can dramatically reduce your risk of cognitive decline as you get older.

Our recommendations are firmly buttressed by a most important article available for free download at the website of the Journal of the American Medical Association.

We already knew that cognitive training can improve cognitive abilities in older adults but nobody had established the effects of cognitive training on everyday function.

Sherry Willis of Pennsylvania State University led a team of scientists that followed a group of 2,832 adults, aged 65 and older -mean age 73.6 years - who were still living independently between 1998 and 2004. The seniors came from all walks of life, races, and parts of the country, including Birmingham, Alabama; Detroit, Michigan; Boston, Massachusetts and three other major cities. They all had one thing in common when the study commenced: they had no signs of cognitive impairment.

The researchers divided them into four groups of roughly 700 each: three groups that would receive training in either memory (verbal episodic memory), inductive reasoning or speed of processing (visual search and identification) with 4-session booster training at 11 and 35 months after training, and one that would serve as a control.

The memory training program consisted of mnemonic strategies for remembering word lists or texts, such as associating various words, visualizing them or organizing them in specific ways. Reasoning training taught the participants how to spot the pattern in a series, such as "a c e g i... ." The researchers boosted the subjects' processing speed via practice, practice, practice in identifying an object on a screen after increasingly short exposures.

Over the course of the next five years the researchers asked participants to appraise their skills and to report whether the training had helped with everyday tasks. They also independently evaluated the subjects' skills in things like finding items in a medicine cabinet. After training, 87 percent of the speed trainees, 74 percent of the reason trainees and 26 percent of memory trainees showed immediate improvement. That advantage over their untrained peers persisted over the next five years.

The training seemed to largely offset the cognitive decline suffered by nearly all of the controls as the years wore on. By the fifth year, significant skill gaps had opened between the people who had done the training  and their untrained peers.

It is not enough to continue to do the crossword or sudoku puzzles. The brain must be continually stretched and challenged. It seems that to drive this effect, you have to practice things that you don't like or things you don't regularly practice.

Many of us have spent years working on new training strategies, and this research shows just how valuable cognitive training can be for all of us.

Genes, Environment and the Brain

We recently looked at the worrying suggestion that environmental toxins could, in susceptible individuals, be contributing to the apparent increase in autism over the last three decades.

There is increasing evidence that there are complex genetic and environmental interactions that contribute to abnormal aging and neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s diseases.

A new study from Duke University Medical Center in Durham, North Carolina, has done more to dissect this interaction. They collected information on 1136 consecutive patients who presented to the Joseph and Kathleen Bryan Alzheimer Disease Research Center. They showed possible significant contributions of toxic environmental and occupational exposures to pathological aging in 21% of the patients, and interactions of these exposures with common genetic polymorphisms that affect cell injury and inflammation. They found a series of genes that could partially account for differences in the type of cognitive problems that people experience, the age at which they developed them as well as the rate of progression.

The researchers targeted three genes in particular - apolipoprotein E, alpha-1-antitrypsin and the hemochromatosis gene. All three are expressed in the liver and in macrophages: cells that play a critical role in immune responses, inflammation and the body’s response to stress and infections. The first two genes are particularly involved in the metabolism of lipids and the third in the balance of iron and trace minerals. This ties in with another observation. Many chronic illnesses are associated with anemia. It is now thought that this also is a defensive reaction. Not to chronic illness, but to the problem that was far more common during evolution, and that was infection. The liver pulls iron out of the circulation so that bacteria cannot use it for their own growth. This is one of a number of adaptive responses that I discuss in the book and CD series, Healing, Meaning and Purpose.

But it was also clear form this new study that genes were not the only factor. I have spoken before about the small number of strategies that can dramatically reduce our risk of developing Alzheimer’s disease. The authors of this study agree about the importance of factoring in environmental factors including, alcohol use, nutritional deficiencies and sleep and mood disorders, all of which can have an impact on cognition.

This study is yet another step toward clarifying the role of genes, inflammation and cell injury in the development of degenerative changes in the brain.

While pharmacologists can use this information to help devise new ways to protect your brain, you can use it immediately. There is a range of behavioral and dietary strategies that can reduce the burden of inflammation in the body. I shall write about some of them in articles and an eBook in the near future.

We do not know whether these strategies can reduce the risk of Alzheimer’s and Parkinson’s diseases, but there are some intriguing suggestions that they can.

Memory Molecules

There are still a great many mysteries about memory:

• The molecules in neurons are constantly changing, as are many of the connections between cells. So how can memory be maintained for a lifetime in an environment that is in a constant state of flux?
• Why is it that you can remove large regions of the brain yet memories are not lost? Even in the late stages of Alzheimer's disease, some long-term memories are maintained even when much of the brain is taken over by plaques and tangles.
• How much memory is there outside the brain and in the body?
• Is some memory maintained not in the brain itself but in fields associated with the body?

Gradually some questions are being answered not just by technology, but by asking new questions and bringing new types of expertise to bear on these problems.

A very interesting new study was published last week in the Journal of Neuroscience. The paper was not by neurologists, but by two mathematicians from the Brain Institute at the University of Utah. Their research suggests that memories are held in our brains because certain proteins serve as anchors, holding other proteins in place to strengthen the connections between nerve cells known as synapses. The anchors keep proteins in place, and these proteins in turn determine how strong a synapse is. And the strength of the synapse is a key to forming and retaining memories.

Synapses function by electrical activity in a neuron releasing a chemical neurotransmitter that affects another neuron or an organ.

One of the primary neurotransmitters involved in learning and memory is called glutamate, that binds to a number of receptors. But the most important for memory are the "AMPA receptors" that are embedded in the receiving ends of neurons. The AMPA receptors are held in place by special scaffolding molecules.

The mathematicians were able to make several predictions about the way in which AMPA receptors stay in place and how repeatedly learning something strengthens the connections between neurons.

The key to learning and remembering is anchoring AMPA receptors on our neurons.

I went into the technical side a bit, because this finding may help us get closer to understanding what goes wrong in Alzheimer's disease.

It also ties in with some other research out this week in the journal Neuron. A team from the Univesity of Oxford has been trying to work out why adults may find learning more difficult than children. The young learn things more easily, but older brains stiore information more efficiently. They also focused on synapses, and  seem to have found the mechanisms involved.

Young brains have many "silent" synapses that don't do anything unless called upon to learn something. Older brains have to reuse synapses that have already been used, boosting the strength of connections with increased amounts of neurotransmitters.

So as we get older, our brains adopt different strategies for learning new material, and we should get ever better at organizing and integrating information.

That also fits with the strategies that we have used for improving people's ability to learn and remember. We use connections as in Mind mapping, multiple sensory associations inclusing music, color and smells, and a sophisticated method for asking constant questions to see if new information fits with material that we have already asimilated.

Links, Citations and References

Following my recent article about mystical experiences, I had a charming note which included this question:

"Could you kindly give a reference or link to the above quote from Ramana Maharshi?"

This was my response:

"I am traveling at the moment, so I don't have access to my library.

Happily I remember exactly where the quote came from. It was from someone who taught me a great deal - the late Paul Brunton. I think that Paul probably did more to introduce Ramana Maharshi to the West than anyone else, and he was also a close friend of Aurobindo. He once commented that it was rather convenient that two of the greatest sages of the 20th century only lived 65 miles apart!

He also mentions Ramana's comment in Chapter 9, paragraph 23 of Volume 16 of The Notebooks of Paul Brunton.

Here's the exact quote:
"That these differences of view exist even among illumined mystics is a striking but rarely studied fact. Why did Ramana Maharshi poke gentle fun at Aurobindo's doctrine of spiritual planes?"

I do not know off hand whether there are any websites that specifically discuss their - respectful - differences of opinion.

If that does not give you what you need, please do let me know: I shall be home in a couple of days and I'd be happy to do a bit more digging in my library: I have over 12,000 volumes, and there are quite a lot of lesser known titles in there. Since I raised it, I shall also have a look online when I get home.”

The reason for re-printing this correspondence is this. Regular readers will know that my blog entries are festooned with links, citations and references. That is very deliberate. This blog is a bit different from most of the other medical ones out there in that I try to ensure that you can check everything that I say.

The other day I had the privilege of speaking to the Rotary Club of New York and mentioned that I had written something about five strategies that can dramatically reduce your risk of developing Alzheimer’s disease as well as discussing some of the evidence concerning nutrition and neurogenesis: the production of new neurons. I was asked what they were, and I recommended that people asking the question should check out the article. The reason was simply this: I wanted them to see the evidence for themselves.

I think that we have all had enough of people simply expressing opinions.

Now is the time for people who are writing on line – or anywhere else for that matter – to provide data to support what they are saying.

If you need further reading material on any of the topics that I write about, just let me know: I have access to a great many sources that are not always easy to get at.

A Possible Test for Alzheimer's Disease

I was very pleased for some of my former colleagues from the Institute of Psychiatry at the Maudsely in London.

Years of work by the researchers and unstinting support from pateints and their families seems to be bearing fruit.

Professor Simon Lovestone and his team have published an important paper in this month's edition of the journal Brain, which is commemorating the centenary of the first description of Alzheimer's disease. It is very hard to get a paper in to the journal, and the fact that the researchers did, speaks volumes about the quality and importance of their work. The entire article is available online. That was made possible by the Alzheimer's Research Trust who also funded this work: kudos to them for backing this work and for publicizing the results.

What they have done is to develop a blood test that may be able to pick up signs of Alzheimer's disease before people start to show symptoms. They used a process called proteomics - the study of proteins - and found levels of two types of protein in the blood that were only present if people had the condition. We do not yet know exactly what the proteins are.

The researchers are quite rightly being cautious at this point. Nobody wants yet again to raise false hopes. There is also the knotty ethical problem of being able to test for people with the earliest stages of the illness. There is the theoretical risk that medical insurers may deny coverage if someone's test is positive.

But if confirmed, this is of enormous importance: we already know that the earlier that treatment is started the better. And by treatment I certainly do not simply mean medications: controlling blood pressure, glucose and lipids; maintaining optimal nutrition; and taking physical and mental exercise may all slow progression of the illness.

It's wonderful to have some good news about this often devastating illness.

Alzheimer’s Disease

To commemorate the hundredth anniversary of the first description of Alzheimer’s disease, there’s a very good review article by John Hodges from the University of Cambridge in the November issue of the journal Brain, which was published this morning.

I first met John when we were both teenagers, and even then his writing was a model of clarity. This new article is excellent, and if you have any interest at all in Alzheimer’s disease, I would urge you to read it. The journal has kindly made the entire article available for free through a grant from the British Medical Research Council.

The most important point of the paper is that our understanding of this devastating illness is progressing by leaps and bounds.Yes, there is still a lot that we don't know, but some ingenious research is opening up a good many new avenues for prevention and treatment.

Testosterone and the Death of Brain Cells

I’m sure that you’ve heard the Robin Williams joke, “See, the problem is that God gives men a brain and a penis, and only enough blood to run one at a time.”

Well it may turn out that Robin was right for the wrong reason.

Typically thought of as the “male hormone,” testosterone plays key roles in maintaining health and wellness in both men and women. It is true that most men produce about twenty ties as much testosterone as women, but in both sexes, it is involved in energy, libido, and immune function and helps protect against osteoporosis. It is also essential for the normal development, growth and functioning of the brain. In small amounts it may also be neuroprotective.

However, too much of a good thing can quickly turn bad. Researchers from the Departments of Pharmacology and Cellular and Molecular Physiology at Yale University in New Haven, Connecticut have just published an important study of apoptosis or programmed cell death in neurons exposed to excessive amounts of testosterone. Apoptosis is a process for disposing of un-needed or unwanted cells, but if it gets out of control, it can begin to remove cells that should have been left alone. Apoptosis is thought to pay a role in illnesses including Alzheimer’s disease and schizophrenia.

While too much testosterone destroyed nerve cells, estrogen appeared to be neuroprotective: there was less cell death in the presence of the hormone.

This new finding has a number of important practical implications.

Testosterone is one of the hormones abused by some athletes. It certainly can enable them to pump up their muscles, but it may also make them aggressive. Now we know that the practice may also kill neurons. And loss of brain cells is associated with a loss of brain function. This is yet another reason why people should think long and hard before they try to use testosterone supplements. The concentrations used in the experiments were very close to what we might expect to see in someone supplementing with the hormone.

These effects of testosterone on neurons will likely have long term effects on brain function. Though you do generate new connections and some new neurons throughout life, there is a limit to how many you can put back, once they've been tainted by testosterone.

And since this is election year here in the United States, I’m sure that we’re now going to have to have a string of off-color jokes about the esteemed Governor of California….

Aging, Skin and Cancer

There’s a very interesting paper in this month’s issue of the journal Developmental Cell, based on research conducted at the Oregon Health & Science University in Portland, Baylor College of Medicine in Houston and Leiden in the Netherlands.

The investigators have found a pathway through which a gene's over-expression causes stem cells in the skin to switch from creating hair follicles to creating sebaceous glands. This discovery may not only provide us with new ways of treating hair loss and oily skin, but it may help us to prevent and treat some cancers.

Skin cells turn over very quickly: just think how fast a graze gets covered over. Epidermal stem cells give rise to the outer layer of the skin that serves as a barrier for the body, as well as generating the follicles that produce hairs and sebaceous glands. These glands produce oils to lubricate the skin. In aged skin, a protein called Smad7 is overproduced, which triggers hair loss and sebaceous gland growth.

This is the first study definitively to link Smad7 over-expression and the pathological changes that occur in aged skin.

Here’s the twist: Smad7 shuts down signaling of another group of genes called Wnt. It binds to a Wnt signaling protein known as Beta-catenin and degrades it with an enzyme called Smurf2. (I don’t known why they decided to call it’s call it Smurf: it looks like ponderous chemical humor to me!) Wnt signaling is critical for organ development, but if Wnt signaling is too active, it also causes cancer.

Enhanced Beta-catenin signaling contributes to many types of cancer, including colon, lung and brain. Perhaps inducing over-expression of Smad7 or delivery of Smad7 directly to tumor cells would provide a therapeutic approach because of the boost in Beta-catenin degradation.

And finally, impaired Beta-catenin signaling contributes to neurodegeneration, such as that found in Alzheimer's and Parkinson’s diseases, retinal degeneration, some bone density defects and aging. For these diseases, blocking Smad7-mediated Beta-catenin degradation may offer a therapeutic approach.

Dementia

I have written about Alzheimer's disease in the past, but it is important for everyone to know that not all dementia, and certainly not all memory loss, is Alzheimer's disease.

There is a brief article on the Psychiatric Resource Forum website that will point you toward some extra resources.

Our biggest interest is always in ensuring that someone who seems to be developing a dementing illness doesn't actually have one of the large number of remediable causes of cognitive decline, such as depression, an underactive thyroid, vitamin B12 or folate deficiency, or an unusual condition called normal pressure hydrocephalus.

Curry and Cognition

During a visit to Singapore a couple of years ago, I heard about some interesting research that's just been published in the American Journal of Epidemiology.

The authors did something fairly simple. They took a group of 1,010 people with no evidence of dementia aged 60-93 years, and correlated their consumption of curry with their cognitive performance. Studies like this are not easy: what if more intelligent people like eating curry to begin with? What if sick people can't get out to the local curry house? And so on.

But the researchers did this all very carefully: they took into account all the known sociodemographic, health, and behavioral determinants of performance on a simple cognitive test. So they controlled for many of the other factors that can accelerate cognitive decline, like depression, smoking, drinking alcohol, high blood pressure, glucose and lipids.

The result was that people who occasionally or often ate curry had significantly better cognitive function than people who "never, or rarely" ate curry.

Is there any logic to this?

Well in fact there is. Curcumin, from the curry spice, turmeric, has been shown to possess potent antioxidant and antiinflammatory properties and to reduce beta-amyloid and plaque burden in experimental studies. There have been serious suggestions about using active constituents of tumeric to try and prevent the development of Alzheimer's disease.

This research is all very encouraging. The amount of curcumin used in the experimental studies is similar to the amount ingested by having a couple of curries a week, and now the epidemiological study from Singapore suggest that those couple of curries may have a clinically measurable effect.  That's not to say that eating curry three times a day is going to be even better.

All things in moderation: too much curry can play havoc with your digestive processes.

And your relationships....

Parkinson’s Disease, Allergies and Inflammation

The symptoms of Parkinson’s disease have been reported throughout history, but it was first described in the modern era by the great Scottish neurologist James Parkinson in 1817. Even after all these years, we still do not know all that much about what causes it. There’s an interesting study in the August issue of the journal Neurology, which is the official publication of the American Academy of Neurology.

Investigators from the Mayo Clinic used what is known as a case-control design (196 cases and 196 matched controls). What they found was that people who suffered from hay fever or allergic rhinitis, are 2.9 times more likely to develop Parkinson’s disease over a 20-year period.

The researchers did not find any association with autoimmune illnesses such as lupus, rheumatoid arthritis, pernicious anemia or vitiligo. They also did not find any association with asthma.

In addition, people who developed Parkinson’s disease used anti-inflammatory agents less frequently than controls, although this result was not statistically significant. The results may support the hypothesis that there is an inflammatory component in the causation of Parkinson’s disease.

You may ask, “Why on earth would anyone even look at a link like this?” The answer is that there have been previous reports of an association between the use of non-steroidal anti-inflammatories and lower rates of Parkinson’s disease in men but not in women and Alzheimer’s diseases.

This study does not suggest that hay fever causes Parkinson’s disease: it provides evidence for an association between the two. Parkinson’s is probably a group of illnesses with different causes. However, if chronic inflammation around the upper airways could produce inflammation in the brain, we might have a whole new way of preventing a degenerative brain disease.

In a future posting I’ll talk about some natural methods for reducing the burden of inflammation in your body.

Blueberries

One of the principles of integrated medicine is that anything that’s good for you should have more than one benefit. So omega-3 fatty acids may help with cardiovascular health, mood, memory, attention deficit disorder, as well as the health of skin and bones.

Another one is the blueberry. I’ve been sufficiently impressed by the data on the health benefits of blueberries to have been a regular grower and consumer for years. They contain a number of potentially healthful compounds including polyphenols and anthocyanins, which can help modulate and balance the free radical systems of the body. Remember what I said recently about the value of keeping some free radicals in the body? The last thing that we want to do is to be rid of all of them!

There is reasonably good evidence that regularly eating blueberries can support cardiovascular health and there have been suggestions that they may reduce the risk and aggression of cancers of the prostate and colon.

There is also some evidence in animals that some of the components of blueberries may reduce inflammation and the effects of strokes – interruptions to the blood flow in the brain.

As a consumer, I’ve been carefully watching the growing evidence indicating that blueberries – or some of their constituents may have effects on animal cognition, brain aging and the normal neuroprotective mechanisms in the hippocampal region of the brain.

We do not yet have proof that these same effects occur in humans, and there are always three questions when we look at nutritional data:

1. Can we extrapolate from the animal to humans? Mice are not men
2. Are the amounts of blueberries or blueberry extracts even close to what humans could consume without spending all day eating, or getting a terribly upset intestine? There have been countless reports of the benefits of supplements that had to be taken in the most enormous doses to do any good. I’ve mentioned before the problem of L-arginine, which is sold as a “Natural Viagra.” Except that you need to take around nine grams for it to do much good, and most supplements contain less than a tenth of that. Regular readers will also remember my report concerning an article on coffee and sex. It was said that coffee would raise a woman’s libido. And indeed it does, if she drinks at least ten large cups of coffee at once. And coffee is a marvelous diuretic.
3. When extracts are used, are we sure that we are getting the correct ingredient of the fruit? Many beneficial fruits contain just the right combination of nutrients to help us, so each can be taken in a small dosage or concentration. As with so much in integrated medicine, combinations are key. Take out one extract of a fruit, and you may lose the clinical effect that you wanted.

All that being said, the evidence is becoming progressively more interesting, and there is enough suggestive evidence for me to keep packing away the blueberries.

And just to show that I leave no stone unturned when checking the literature on your behalf, I rejoiced to learn that supplementing the diet of Arctic char with various supplements - including blueberries – improved the quality of his, ahem, semen. I do not know how this information will help any of us yet. Neither do I really know why a fish would want to eat blueberries or any of the other supplements that they were tried on. Though I'm sure that people have often asked similar off the wall questions about some of my research....

Psychotropic Medicines and Neurogenesis

One of the genuine breakthroughs of the last few years has been the understanding that the brain is not a static structure, but is instead an organ that grows, refashions and repairs itself to a remarkable degree.

You may be interested in a brief review article looking at the effects of some of the medicines that appear able to stimulate neurogenesis in the adult brain.

It is no longer far-fetched science fiction to say that we are likely soon to be able to regenerate parts of the brain and spinal cord that have been damaged by disease or trauma. And in the meantime, we have an array of stratgeies that you can adopt to keep your brain active throughout life, while dramatically reducing your risk of developing dementia.

Technorati tags: Neurogenesis Antipsychotics Antidepressants Brain repair

A New Way of Looking at – and Treating - Inflammation

Diseases of both large and small blood vessels are two of the biggest problem facing people with diabetes. Not only is it a huge clinical challenge, but also nature sometimes does our experiments for us. The high rates of coronary and peripheral vascular disease in diabetes can be seen as a kind of experiment of nature: a recognizable set of chemical abnormalities that might shed light on vascular diseases in general. It was those twin factors: a huge clinical problem, and an experiment of nature, that lead me to pick the topic of my research doctorate. 

When I was working on my research doctorate in the mid 1980s, I came across a lot of old research that seemed to show links between inflammatory and autoimmune conditions like systemic lupus erythematosus and rheumatic fever, and the eventual development of coronary artery disease. There was also a lot of old and largely forgotten research about the link between some viral infections and the development of coronary artery disease and acute coronary artery occlusions, because some infections can make blood more “sticky.” Inflammation evolved as one of the body’s defence mechanisms.

So I made the proposal – revolutionary at the time – that diabetes, coronary artery disease and a range of other illnesses might be inflammatory rather than degenerative. I soon found inflammatory markers in people with diabetes, that helped predict when someone was running into trouble with their eyes, kidneys or heart.  Even with stacks of data, I had to spend a lot of time defending that position, because it also implied that some illnesses thought to be irreversible might not be.

With the passage of time, it has tuned out that I was probably correct. Chronic inflammation, wherever it starts, mat have long-term effects on the body and on the mind. Chronic inflammation increases the risk of diseases of many blood vessels, as well as causing anemia, organic depression and cognitive impairment. Here is a partial list of common conditions in which inflammation is a prominent factor:
1.  Rheumatoid arthritis
2.  Systemic lupus erythematosus
3.  Fibromyalgia
4.  Chronic infections
5.  Insulin resistance or metabolic syndrome
6.  Arteriosclerosis
7.  Diabetes mellitus
8.  Hypertension
9.  Asthma
10. Inflammatory bowel disease
11. Psoriasis
12. Migraine
13. Peripheral neuropathy
14. Alzheimer’s disease
15. Autism
16. Gingivitis
17. Cystitis

The reason for raising the issue is not to say “told you so!”

It is instead that we need to think about inflammation a little differently. There is a mountain of information about the physical aspects of inflammation. We can stop at the simple description of inflammation as a condition in which part of the body becomes reddened, swollen, hot, and usually painful, or we can look below the surface: we can examine inflammation not only as a physical problem, but also as a psychological, social, subtle and spiritual problem. Why bother? Because the deeper approach allows us to understand and to treat and transcend inflammation as never before.

I am going to write some more about specific ways to address inflammation and what it means in future articles. I would also like to direct you to the book Healing, Meaning and Purpose, in which I talk about specific approaches in more detail.

But I would like to start with this.

In Ayurvedic and homeopathic medicine, inflammation is a sign of an imbalance in the vital forces of the body, and the traditional Chinese system agrees: here inflammation is usually a manifestation of an excess of Yang Qi, or a deficiency of Yin Qi. Most of our lives are seriously out of balance: Yang Qi is like a rampaging lion that has been stimulated by:
Acidic foods;
Environmental toxins;
Unwanted sexual stimulation:
Noise;
Discordant music:
Constant demands from others:
Toxic relationships;
Years spent in front of television sets and limitless multi-tasking.

It should be no surprise to learn that all of these inflammatory conditions are increasing rapidly throughout the Western world. Not because we are getting better at identifying them, or we are living longer, but genuinely increasing.

It is wrong to put all the blame on poor diets or inadequate exercise. The problem is more subtle and is a reflection of distorted Information being fed to our bodies, minds, relationships, subtle systems and spiritual relationships.

The great news is that this simple conceptual shift gives us a whole load of new tools for handling these problems, and for using them as catalysts to growth.

In the next few weeks, I am going to drill down and give you some specific guidance that ties into the material in Healing, Meaning and Purpose and the next two that are on the launch pad.

Fasten your seat belt!

Technorati tags: Inflammation Aging Alzheimer's disease Arteriosclerosis Neuropathy Autism Arthritis Systemic lupus erythrmatosus Fibromyalgia Inflammatory bowel disease Gingivitis 

Integrated Health and Aging

An important principle of the emerging laws of health and healing is that anything helpful should help more than one system of the body at a time. So a diet that might help mitigate the effects of aging in the skin should also have beneficial effects on the major organs of the body.

So I was encouraged to see a new report indicating that cardiovascular health and a healthy lifestyle are associated with maintaining the health of our brains as we age. This is, of course, intuitively obvious, but it is always nice to see such things confirmed by empirical research.

The new report is from a multi-Institute collaboration of the National Institutes of Health (NIH) published online in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. The chair of the committee was Hugh Hendrie, the Scottish-born professor of psychiatry from the University of Indiana, and the committee members were many of the most eminent people in the fields of aging and Alzheimer’s disease.

What is encouraging about this new report is that many of the factors associated with cognitive decline as we get older are eminently remediable: we have within our reach a set of potential interventions that could significantly reduce our personal risk of developing cognitive problems later in life. These are the things that we need to work on if we want to reduce our risk of developing cognitive decline later in life:

1. Hypertension: There is excellent evidence that inadequately treated hypertension correlates strongly with cognitive decline.
2. Physical activity: There is good evidence that elders who exercise regularly are less likely to experience cognitive decline. This is over and above the general improvement in quality of life that accompanies regular exercise. The earlier in life that we start, the easier it is to continue.
3. Increased mental activity throughout life, including learning new things and going through higher education may benefit the health of the brain.
4. Moderate alcohol use and the use of vitamin supplements also seem to be brain protectors, though the report does not specify which supplements.
5. Social disengagement and depressed mood are both associated with poorer cognitive functioning, so it is important to be alert to signs of depression, and to maintain a social network. I discuss this in more detail in my book Healing Meaning and Purpose.

There are doubtless some genetic and environmental factors about which we can do little. But the idea that we now have a list of things that we can do to protect our brains is very exciting.

This report also signals another important change. In recent years we have seen the growth of Positive Psychology, the study of how to improve ourselves rather than the constant focus on psychopathology. This report calls for the research community to study health maintenance of the brain with the same energy that it has brought to bear on the study of diseases of the brain. To which I would add, that we must not just focus on how to maintain the health of the brain, but how we can enhance it’s function so that we can all reach and exceed our full potential.

Technorati tags: aging, Integrated health, Positive Psychology, healthy lifestyle,