This week Bryce Vissel from the Sydney Garvan Institute of Medial Research was on ABC radio discussing the results of the study that had been published in the 29th September edition of PLoS One.

Researchers from Australia and the States have identified a new way that the brain can create memories and store information. The implication of this is that this new pathway may prove useful to provide new and alternative ways of treatments where there has been brain injury or death, such as with stroke and Alzheimer’s disease.

The way our brain works to store memories involves the hippocampus where an essential mechanism called the NMDA receptor is involved. When the NMDA receptor is activated, calcium is allowed to enter the brain cell, which then triggers further molecular reactions resulting in our brain being able to process, store and recall information.
Our understanding over the last twenty or thirty years has been that learning could not take place without these receptors. The scientists were looking to replicate the mechanism artificially and coincidentally uncovered an existing second system that the brain already has in place. In this second system a different receptor called AMPA does the job of encoding memory, but appears only to be activated when the information received is similar to something we have previously learnt. This is called second learning.

The questions now being raised from this finding is to work out what causes this second mechanism to operate. Then it may be possible to look for ways to get it to take over the role of the NMDA mechanism if that isn’t working because of disease or injury.
It might then be used to protect us against conditions such as Alzheimer’s (where the ability to form new memories is lost), because it could be that stimulation of this alternative pathway would then help us to keep participating in memories.
The other potential implication of this finding is that having this second means of learning could have really important effects on how we approach teaching in the classroom in the future as well.

Ref: A Role for Calcium Permeable AMPA Receptors in Synaptic Plasticity and Learning.
Wiltgen BJ, Royle GA, Gray EE, Abdipranoto A, Thangthaeng N, et al. 2010 A Role for Calcium-Permeable AMPA Receptors in Synaptic Plasticity and Learning. PLoS ONE 5(9): e12818. doi:10.1371/journal.pone.0012818

US $604 billion

That’s the figure given for the worldwide cost of dementia for 2010.
It’s the equivalent of more than 1% of global GDP

That’s just for this year.

The figure comes from the World Alzheimer Report 2010 by Alzheimer’s Disease International (ADI), which provides the most current and comprehensive account of the true economic and social costs of this disease.
ADI is an international federation of 73 Alzheimer’s associations who support those living with dementia and their families.

Are you ready for some more statistics?

• If dementia were a country it would be the world’s 18th largest economy.

• If dementia was a company it would be the world’s largest by revenue, bigger than Wal-Mart ($US $414 billion) and Exxon Mobil (US$311 billion)

The cost of caring for people with dementia is staggering. People with dementia live for many years, gradually requiring increasing levels of support. In the early stages carers can provide extra help around the home to help with shopping, cooking, housework, laundry and transport to and from medical appointments.
There are also Day centres, Memory café’s and respite facilities that provide fantastic support to the person with dementia and their families.
Then there are dementia specific aged care facilities which provide care for those no longer capable of looking after themselves and need help with all basic activities of daily living such as dressing, eating or simply moving around.

That doesn’t even touch the emotional cost of the disease on families trying to cope when a loved member of the family has dementia. They have to cope with the slow inexorable decline and see the person they once knew gradually fade away into a shell of their former selves.
It is forecast that the cost of caring for people with dementia is likely to rise faster than the prevalence especially in the developing world.

UK reports have suggested that dementia is one of the costliest illnesses to manage.
Professor Ralph Martins from Perth’s McCusker Alzheimer Research Foundation spoke recently about the continuing problem of having to seek sufficient Government grants to continue their valuable research into the disease. Currently, the amounts given for dementia research and investment remains far behind that for heart disease and cancer.

Again going back to UK data, research funding would need to increase by x15 to reach parity with that given to heart disease and x30 to achieve parity with cancer research.

Here in Australia we do have a National Plan to deal with the social and health implications of Alzheimer’s. This is at least a step in the right direction.
However plans need to be made visible and they also have to be implemented to be of any actual value to their population.

It appears that while there is acknowledgment that we are facing a global crisis as the number of people affected by dementia is forecast to escalate exponentially, there appears to be a serious lag in terms of government response to be prepared to deal effectively for this.

Here in West Australia, 23,000 people are currently living with dementia.
This is expected to rise to over 100,000 by 2050, a 375% growth.

Overall in Australia there are around 257,000 people currently living with dementia, which is expected to increase to 1.1 million by 2050.

Around the world there were 35.6 million people with dementia in 2009, around 0.5% of the world’s total population.
This has been forecast to rise to 65.7 million by 2030, to 115.4 million by 2050.

What will be the global cost to the economy then?

The report can be read at www.alz.co.uk/worldreport

It is sobering reading.

However we cannot afford just to sit by and wait and hope for a cure.
We can however be responsible for our own brains and start to put in place simple lifestyle choices to help preserve our own cognition and follow a brain fitness program. This isn’t hard, it’s just something we need to do and we can do.

If we all undertook some initiative to help preserve our brains, to help diminish our risk of developing Alzheimer’s or dementia or defer it’s onset, then we can all contribute significantly to diminish the bourgeoning global cost to us all, as well as being able to continue to enjoy the benefits of keeping all our marbles.

It’s not rocket science. We can all enjoy good nutrition, and make an effort to remain physically, socially and mentally active.

And we are all capable of doing that.

Research on finding better ways to better diagnose, treat and ultimately prevent Alzheimer’s disease is being investigated around the globe on massive scale. Some researchers are concentrating on ways to prevent amyloid build up; others are looking at ways to increase brain functionality.

Neuroscience has provided us with a far greater understanding of how our brain can adapt and rewire itself throughout our lives. The role of diet has been shown to be vital in helping our brain cells to function and be maintained at their best. Many different studies have examined different micronutrients, the vitamins and minerals we eat, to see what impact they may have in helping us to keep our brains healthy.

This week I received a copy of a report published in the UK on the findings of a research study looking at the effect of B vitamins on brain shrinkage. This was a small trial in Oxford, looking to see whether administering large doses of B vitamins would lower homocysteine levels in the blood and lead to less brain atrophy in elderly subjects who already had mild cognitive impairment.

Our shrinking brain.

Our brains start to shrink from the time we are in our early twenties. Not by much, around 0.2% per year. But once we reach the age of 60, the rate of shrinkage starts to increase to 0.5% per year.
In mild cognitive impairment (MCI), a person is having problems with memory loss, language difficulty and other problems beyond those normally expected simply through ageing.

Around 16% of people over the age of 70 years develop MCI and half of these people subsequently go on to develop Alzheimer’s disease. MCI is seen as a precursor for Alzheimer’s.
In MCI the rate of brain shrinkage increases to 1% and by the time Alzheimer’s is diagnosed is around 2.5% per year.

Homocysteine and the B Vitamins

Homocysteine is an amino acid normally found in the body. Our B vitamins help to keep it in the normal range. In excess it has been shown to be a risk factor for heart disease, brain atrophy, cognitive impairment and dementia.

In a previous blog post I looked at a study on women, which had shown that using measurements of blood homocysteine levels could determine a woman’s risk factor for dementia.
It is known that homocysteine levels can be lowered in the body by administering doses of the B vitamins.
The Oxford study looked to see whether using large doses of the B vitamins would lower homocysteine levels and thereby reduce the rate of brain shrinkage in subjects with mild cognitive impairment.

Big doses of Vitamin B

In the trial, very large doses of B vitamins were used: x300 the RDI for vitamin B12, x15 for Vitamin B6 and x4 that for folic acid.
The co-author Helga Refsum from the University of Oslo indicated that in this study the vitamins were being used as a drug rather than simply vitamin supplementation. It is unknown if these megadoses have any long-term effects and there have been studies linking high dose folate to an increased risk of cancer.

168 people over the age of 70 years who had been diagnosed with mild cognitive impairment were divided into two groups. One group received the mega dose vitamins and the other group received a placebo.
MRI scans were used to measure brain volume at the beginning of the study and then annually over a two year period.

The results showed that in the group taking the vitamins, the average reduction in the rate of brain atrophy was 30%. Moreover those who had had the highest level of homocysteine at the beginning of the study, showed the greatest reduction in shrinkage rate by up to 53%. Those who had received the vitamins also performed better overall on mental testing.

The inference was that this may be a way to help reduce the number of people with mild cognitive impairment from progressing to full blown Alzheimer’s.
The “how” of lowering homocysteine to produce this brain saving effect is not yet known. Being such a small study the results while encouraging will now be followed up with a much larger study to verify the findings.

Where to from here?

The B vitamins are known to be important in helping us to maintain a normal nervous system.
We can obtain our B vitamins from diet. Some of our foods are already fortified with B vitamins especially folic acid. The role of folate in helping to prevent neural tube defects (spina bifida) in babies is well documented.
Good sources of B12 are found in fish, milk ,eggs and chicken.
Vitamin B6 is found in beans , meat, poultry, potato, banana and tuna.
Folate (folic acid) is found in green leafy vegetables and fortified breads and cereals.

So we can enjoy a wide range of foods to provide us with a good intake of the B vitamins. We can already measure homocysteine levels by a simple blood test and it is easy enough to take vitamin B in supplement form. It just remains too early yet to recommend taking big doses to preserve our brains.
What is particularly encouraging from this study is that it may provide a simple and inexpensive treatment to reduce the number of people already with MCI from progressing to full blown Alzheimer’s disease.

Ref: Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, et al. (2010) Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial.

A little ray of sunshine for Parkinson’s disease may lie with Vitamin D.

Vitamin D is the vitamin we obtain through the action of ultraviolet light on our skin. Most of the vitamin D produced is then bound in the blood and only a tiny fraction remains free and able to bind to specific vitamin D receptors now known to be located in a number of target organs in the body including the brain.

Not only that, but the area of the brain with the highest density of Vitamin D receptors is in the Substantia Nigra. This is where highly specialized cells produce Dopamine, the brain neurotransmitter vital for regulating our mood, concentration, motivation and voluntary movement.
In Parkinson’s disease many of these highly specialized cells die and the loss of Dopamine manifests itself in the form of tremor, rigidity of movement, slowness of gait and cognitive decline. Plus, thirty percent of people with Parkinson’s disease develop dementia.
It is the second most common neurodegenerative disease in Australia and remains one of the most poorly understood.

So where does Vitamin D fit in with Parkinson’s disease?

The answer to that is not yet certain, but a recently published study has linked having a higher level of Vitamin D with up to a 65% reduction in the risk of developing Parkinson’s.

These results were in a long prospective study by Paul Knekt in Finland. He showed that in a group of 3173 people aged 50 to 79, followed up over a 29 year period, those with a higher level of Vitamin D had a 65% lower risk of developing Parkinson’s compared to those with the lowest levels.

However it should be noted that all of the subjects in this study actually had lower levels of vitamin D than is recommended. This may reflect the fact that Finland is not a country associated with a lot of sun exposure for its residents. So the suggestion is that having a lower level of Vitamin D may be a predisposing factor to an increased risk of Parkinson’s disease. There is no suggestion that having a low level is in fact a cause. The study remains a starting point to determine whether giving Vitamin D as a supplement would be useful.

One of the problems recognized is that Vitamin D deficiency is widespread, even in a sunny country such as Australia. It has been reported that half to two thirds of teenagers and adults in the US have lower than desirable levels. Because it is very difficult to get sufficient Vitamin D through our diet, having adequate sun exposure is essential to help us achieve and maintain a healthy level.

How much time do we need in the sun?

Five to fifteen minutes of sunlight exposure to the face and upper arms, four to six times a week is thought to be sufficient to prevent deficiency.
Those particularly at risk of deficiency here in Australia include the elderly living in residential care and dark skinned women, especially those who are veiled. The use of sunscreen (essential to protect us from skin cancer) unfortunately prevents the synthesis of Vitamin D in the skin. Application of Factor 8 will prevent up to 95% of Vit D conversion, so a short exposure without sunscreen is recommended and outside the high-risk times of 10 am to 3 pm.

Can we get Vitamin D from our food?

We can derive a limited amount of Vitamin D from food sources. However in cases of deficiency taking a supplement would be recommended.

Vitamin D2 can be found in:

Fatty fish such as mackerel, salmon and herring
Fortified margarines
Cod liver oil
Liver
Eggs

The role of Vitamin D in the brain

The association of Vitamin D and Parkinson’s disease is intriguing and as yet not fully explained. It is believed that Vitamin D acts as a hormone rather than a vitamin, in addition to its role in bone metabolism.

Current thinking is that it may exert a neuroprotective effect through its antioxidant properties, calcium regulation of nerve cells, enhanced nerve conduction, detoxification and immunomodulation.

A UK study looked at Vitamin D levels of a group of 858 Italian men and women over the age of 65 years. Of those with dementia, 50% were vitamin D deficient. Moreover, those with the greatest deficiency had a 60% increased risk of suffering cognitive decline over the 6-year follow up period.

The role of Vitamin D relating to Alzheimer’s disease was looked at in a 2008 study where 100 people with Parkinson’s disease were compared to 100 subjects with Alzheimer’s disease and 100 healthy controls. Here the fraction of patients with the lowest levels of Vitamin D was most marked in the Parkinson’s group (23%) compared to the Alzheimer’s group (16%) and healthy group (10%) indicating support for the notion that Vitamin D plays a role in affording some neuroprotection.

Meanwhile it remains prudent to ensure that we obtain adequate sun exposure to keep our Vitamin D levels up. So go on, it’s time to enjoy some time in the sun.

References:
Emory University (2008, October 17). Lack Of Vitamin D Linked To Parkinson’s Disease.
Archives of Neurology [2010] 67 (7) : 808-811 (Knekt P, Kilkkinen A, Rissanen H, Marniemi J, Sääksjärvi K, Heliövaara M.)

Statisticians have been telling us how Western societies are facing a tsunami of people developing dementia and Alzheimer’s over the next couple of decades. This is associated with our ageing population; we are all living longer, so our relative risk of developing dementia rises as well.

What worries me though is the fact that we seem to be ignoring the impact that the dramatic increase in people living with Type 2 diabetes and obesity will have on these figures.

Both diabetes and obesity are known risk factors for dementia.
Adults who develop diabetes before the age of 65 have twice the risk of developing dementia compared to non-diabetics and also have an increased risk of depression.

It is our children that worry me the most. Twenty years ago the number of kids diagnosed with Type 2 diabetes was in the order of 2%. It was an extremely rare condition. Now 30 to 50% of all those diagnosed with Type 2 diabetes are between the ages of 9 and 19 years. Those aged in their thirties, have seen a 70% increase in the number of people diagnosed.
The scary thing also, is that it is known that there are an even greater number of people with undiagnosed diabetes in the general population.

What is Type 2 diabetes?

When we eat a meal, the carbohydrates in it are broken down and released into our blood stream as sugar, leading to an increase in the blood sugar level. This then stimulates the pancreas gland to release insulin hormone which works to restore the blood sugar level back to normal by sending the glucose to tissues that need it for energy, or for storage. If the body is repeatedly overloaded with excess glucose, the body’s ability to respond to the insulin is diminished, leading to a condition called insulin resistance. Increasing amounts of insulin then get produced, but it can no longer exert its effect. This is the condition of Type 2 diabetes where blood sugar levels are consistently too high and associated with elevated insulin levels.

It is distinguished from Type 1 diabetes where the specialised glands in the pancreas are unable to produce insulin.

When are we going to wake up to this risk?

If you have diabetes, you have a higher risk of cognitive decline and dementia.

In a study of 2300 older women aged 70 to 78, non-diabetics on mental testing scored twice as high as diabetics. It was also found that the longer the person had had diabetes, the more poorly she performed.

In another multiethnic, multicenter study of 10,000 people, the results of cognitive tests taken 6 years apart were compared. In the 40 to 70 year age group, diabetes was again linked to greater cognitive decline.

What does diabetes do to the body and brain?

Diabetes affects multiple organs in the body including the blood vessels, heart eyes, brain and kidneys and is insidious in how it gradually erodes cognitive ability. Elevated blood sugar levels contribute to hardening of the arteries, (atherosclerosis) which increases the risk of heart disease and stoke. In the brain, this vascular damage is linked to an increase in small infarcts (injury to small arterioles in the brain) or tiny strokes. Having persistently elevated blood sugar contributes to damage of our brain cells, brain atrophy and cognitive impairment. The loss of brain cells is especially prominent in the area of the hippocampus, the specialised brain area concerned with memory and learning.
Diabetic patients who have developed diabetic retinopathy have been shown to have twice the risk of developing cognitive impairment.

Excess insulin also contributes to the brain damage. It has been discovered that the brain has it’s own insulin receptors. Increased insulin levels have been linked to increased levels of amyloid, the protein associated with plaques found in Alzheimer’s. Excess insulin also has a role in stimulating inflammation, and reducing the levels of acetylcholine an essential neurotransmitter for memory.

But it’s not just diabetics who are at risk of impaired brain function and reduced mental performance. It has been shown that drinking a sugary glucose drink will adversely affect your ability to perform memory tests. So the key is to avoid big swings in blood sugar levels.

Because we know that diabetes is associated with an increase risk of cognitive impairment and dementia, it is vital that the message gets out to all those at risk.

The good news though, is that we know that good lifestyle choices can have a hugely beneficial effect on blood sugar control.

The aim is to

• Keep blood sugar levels in the normal range
• Maintain a healthy body weight
• Eat a nutritious and brain healthy diet low in saturated fat
• Exercise for 30 minutes a day by walking or other moderate intensity activity.

My question to you is this. Can we afford not be taking immediate steps to educating people to fully understand the consequences of “accepting” the recent global increases in obesity and diabetes?

Our sweet tooth is killing our brain.

Refs:
Roberts et al. Association of Duration and Severity of Diabetes Mellitus With Mild Cognitive Impairment. Archives of Neurology, 2008; 65 (8): 1066 DOI: 10.1001/archneur.65.8.1066
University of Southern California (2009, January 28). Getting Diabetes Before 65 More Than Doubles Risk For Alzheimer’s Disease.