As we reach our forties and fifties, we start to notice a few changes with our brain. We forget things more easily, we experience more “tip of the tongue moments” and find it harder to stay focused or on task. We put it down to the fact that our speed of mental processing is slowing down. We may even have a couple of fleeting worrying thoughts that our brain might be showing the first signs of actual cognitive decline.

One of the biggest fears people express about ageing, is the loss of our mental faculties. That loss of that of course, has a significant impact on our ability to remain self-caring and independent.

Until now, the onset of actual cognitive decline has been thought to occur in our sixties. The clinical onset of Alzheimer’s disease typically occurs around age 65 or older, although it is well recognized that the actual condition slowly and silently develops over the preceding couple of decades. Brain scans can now show the pathological changes in younger brains, before the clinical signs of disease.
Those showing the greatest amount of pathological change in their brains are also known to be at greatest risk of developing clinical signs of dementia in later life.

Findings from a couple of studies (including a longitudinal study from Seattle, which has been following a group of 500 individuals since 1956) have suggested that cognitive decline did not start before the age of 60.
Those findings have now been challenged by a new study recently published in the British Medical Journal which has found that the age of onset of cognitive decline may be significantly earlier than previously thought: actually starting in our mid forties.

This study of 10308 men and women civil servants aged 45 to 70 years from London UK was set up to examine whether different age groups showed differing levels of cognitive decline over a ten-year period. The group underwent tests of memory, reasoning, vocabulary, phonemic and semantic fluency in three different assessments over the ten-year period.

The results of the study showed the following:

Between the age of 65 and 70, men on average showed a -9.6% decline in cognition,
women -7.4%. This was not unexpected.

However results of the younger age group age 45 to 49 also showed evidence of cognitive decline, albeit at a lower percentage; -3.5% cognitive decline for men and -3.6% for women.

The implications of this study suggest that we need to be taking a much closer note of how we are performing in midlife. Along with midlife obesity, high blood pressure and high cholesterol, our midlife cognitive function appears to be very important in determining how we will fare as we age.

If cognitive decline is picked up in our midlife, then at least that provides some valuable time to be putting into place specific strategies to to minimize any further decline and attempt to build cognitive reserve. What we don’t know (and requires further study) is whether midlife cognitive decline will lead to actual dementia – however it would seem prudent to do whatever we can, to keep our brains intact.

So what is the best thing we need to be doing in our midlife?

It’s all about maintain and improving brain function by adopting brain healthy lifestyles:

Eat healthily with a wide variety of green vegetables, fruit, lean proteins, seeds and nuts and keeping away from pies, pasties, cakes and biscuits, hot chips and fried foods.

Maintain a positive attitude to life. Being social engaged and active helps to keep stress levels down and stave off anxiety and depression.

Use your brain to learn new skills. Aim to include mental activities every day that are outside our usual habits. Card games, Sudoku, brain games, and apps are all useful.

Move your body. One of the biggest things we can do for our brain is to ensure we spend a minimum of thirty minutes every day doing some form of physical exercise – enough to get the heart rate up.

So next time you have a memory lapse, forget an appointment or lose your keys while it might simply a slower speed of processing, it could be an indication of a more serious reduction in your cognitive ability. So rather than ignoring it, be proactive and take the time every day to help restore your mental sharpness. Your brain may depend on it.

Ref:

Singh-Manoux,A.et al Timing of onset of cognitive decline: results from Whitehall 11 prospective cohort study. British Medical Journal 2012; 344 doi: 10.1136/bmj.d7622

It’s always good to hear encouraging news, especially when it is about a potential treatment for Alzheimer’s disease. A recent report on the evening news spoke about a vaccine being developed through the University of Sydney.

Associate Professor Lars Ittner from Sydney’s Brain and Mind Research Institute is leading a study into developing a vaccine that targets a specific brain protein called tau that is associated with Alzheimer’s disease and fronto- temporal dementia.

In people with dementia, the tau protein forms what are called neurofibrillary tangles, which leads to neuronal death and loss of brain function.

In this study on mice, the vaccine was shown to slow down the development of further neurofibrillary tangles. There was no effect on those tangles that had already formed. So the prospect is that it might be possible if future development of this vaccine occurs for this to be be used in humans once the diagnosis of dementia has been made, and slow down progression of the disease. It is not a cure, but it could buy the person more time for cognitive functioning and possibly work as a preventative if someone is perceived to be at higher risk of developing dementia.

Other researchers around the world have also been looking to develop a vaccine, one to either target tau or amyloid.

Professor Ittner commented that in many studies, vaccines were being trialled in mice with dementia, prior to the onset of clinical symptoms. This study is the first to show that a vaccine targeting tau can be effective once the disease has set in. It is known that the pathological changes associated with Alzheimer’s disease start many years before the clinical onset of symptoms. Having a treatment to slow down further progression would be huge step in the right direction.

Earlier this year I wrote a blog about a nasal spray being developed to minimise the potential risk of vascular dementia.

Researchers at Georgetown University, Washington D.C have found that if an antibody is given later in the progression of Alzheimer’s the greater the chance that it will trigger brain inflammation.

In their studies, mice with Alzheimer’s symptoms were given an antibody called PFA1, which was designed to clear amyloid from their brains. Those mice with the greatest amount of amyloid present at the beginning of treatment showed a greater inflammatory response. The take home from this was that the greatest benefit to lower the amount of amyloid would be obtained by using it early on i.e. in the early stages of the disease.

In Germany, researchers at the University of Rostock are investigating a protein ABCC1, which has been shown to help remove amyloid from mice brains. They have also been using a drug commonly used for treating nausea and vomiting (thiethylperazine) to activate this protein, suggesting that using this drug could be of potential benefit to prevent the development of amyloid plaques.

In the US, Scott Webster at the Georgia Health Sciences University in Augusta is also working on an Alzheimer’s vaccine. His vaccine is targeted versus two brain proteins: amyloid and RAGE (receptor for advanced glycation end-products). The RAGE protein helps the amyloid get into the brain and contributes to the inflammatory process that the amyloid causes to the brain’s neurons.

Webster’s vaccine is different in that it targets these two proteins. The vaccine uses the body’s own immune system to protect against the overproduction of RAGE and amyloid. His vaccine is different also in that it can be taken orally thus using the gut’s bacteria which are vital to our immune system. Previous vaccines developed elsewhere that have targeted just amyloid, have failed to show benefit in clinical trails and some have also had significant side effects. By targeting the two proteins, Webster is more hopeful that this combination effect will lead to reducing or eliminating the toxic effects of the brain inflammation. Early results in animal studies have been encouraging so far, so the next step will be to use the vaccine trialled in larger animal studies.

With all this amazing work going on around the world we are surely moving closer to having more effective treatments that will be able to stop Alzheimer’s in it’s tracks.

Refs:

Bi M, Ittner A, Ke YD, Götz J, Ittner LM (2011) Tau-Targeted Immunization Impedes Progression of Neurofibrillary Histopathology in Aged P301L Tau Transgenic Mice. PLoS ONE 6(12): e26860. doi:10.1371/journal.pone.0026860

American Friends of Tel Aviv University (2011, February 28). An Alzheimer’s vaccine in a nasal spray?. ScienceDaily. Retrieved December 10, 2011, from http://www.sciencedaily.com¬ /releases/2011/02/110228104310.htm

Markus Krohn, Cathleen Lange, Jacqueline Hofrichter, Katja Scheffler, Jan Stenzel, Johannes Steffen, Toni Schumacher, Thomas Brüning, Anne-Sophie Plath, Franziska Alfen, Anke Schmidt, Felix Winter, Katja Rateitschak, Andreas Wree, Jörg Gsponer, Lary C. Walker, Jens Pahnke. Cerebral amyloid-β proteostasis is regulated by the membrane transport protein ABCC1 in mice. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI57867

Georgia Health Sciences University (2011, September 26). Research points new way to possible Alzheimer’s vaccine. ScienceDaily. Retrieved December 10, 2011, from http://www.sciencedaily.com¬ /releases/2011/09/110926104609.htm

Having high blood pressure or hypertension is a recognised risk factor for Alzheimer’s and other forms of dementia, particularly vascular dementia.
The simple act of getting your blood pressure checked by your doctor regularly is paramount.

You can’t tell when your blood pressure is up. But your doctor can. Keeping your blood pressure within the normal range is very important for both heart and brain health.

There are some simple lifestyle choices, which can help keep your blood pressure normal:

• Keep your weight in the healthy range
• Exercise daily – gotta “find that thirty”
• Eat healthily with lots of green leafy vegetables and fruit
• Manage stress levels through exercise, meditation or mindfulness
• Stop smoking
• Cut the salt

If you are doing all of the above and your blood pressure is still too high, then it may be time to consider using an antihypertensive. This is where the choice of which antihypertensive used can possibly make a difference for preventing Alzheimer’s or slowing down the progression of the disease if already present.

At least that what research from a large observational study in the UK has found.
The findings from this study have been published in the Journal of Alzheimer’s Disease and indicate that for older patients (age 60+) being prescribed what is called an angiotensin 11 receptor blocker (ARB) was associated with a 53% lower risk of developing Alzheimer’s disease compared to a 24% reduction for those prescribed an angiotensin converting enzyme (ACE) agent.

These findings come from an observational study of over 9000 patients aged 60+ who were diagnosed at some time between 1997 and 2008 with either probable or possible Alzheimer’s disease or other dementia. The data suggested that being prescribed an ARB or ACE was associated with a lowered risk of developing Alzheimer’s disease, vascular or other dementia. Controlling for control and age, and other illnesses made no difference to the risk reduction and there was also noted to be an apparent dose- response relationship between ARBs and Alzheimer’s.

This research supports the move to now undertake actual clinical trials to verify these findings.

These results support findings from previous studies conducted elswhere. In 2010 a study from Boston University School of Medicine compared the incidence of Alzheimer’s disease and dementia in men taking ARBs compared to either the ACE drugs or other antihypertensives.

Reducing Alzheimer’s incidence and nursing home admission.

In this study a significant reduction in the actual incidence of Alzheimer’s and other dementia was reported as well as a reduction in the rate of disease progression measured in terms of lengthening time to admission to a nursing home or death.

Dr Wolozin reported that those people who did the best were prescribed a combination of an ARB and ACE with 55% reduction in the incidence of Alzheimer’s and other dementias and a 70% reduction in nursing home admissions. Being prescribed an ARD on its own was associated with a 50% reduction of risk of incidence of Alzheimer’s.

This in itself is of major implications as keeping a person with Alzheimer’s or other dementia at home for longer is highly desirable as well as a major cost saving.
In this study, data was collected from the US Veterans Affairs administrative database (this contains information on over 5 million people!) looking at the rate of incidence of Alzheimer’s or dementia being diagnose over a four years period in men over the age of 65 with a history of cardiovascular disease. The subjects were divided into three groups taking either a) an ARB b) taking an ACE (Lisinopril) or c) taking other cardiovascular drugs.
Adjustments were made for age, diabetes, stroke, cardiovascular disease and the findings were that those taking the ARB drugs had a lower incidence of Alzheimer’s and significantly lower risk of being admitted to a nursing home, again with a dose response for the ARB.

So why the difference?

Both ARBs and ACEs work by reducing angiotensin 11 signalling at the level of two receptors AT1 and AT2.
ARBs appear to make the difference by selectively inhibiting the angiotensin 1 receptor.

If the AT1 receptor is stimulated, this leads to vasoconstriction.
If the AT2 receptor is stimulated, this leads to vasodilation, neuronal differentiation and neuronal repair.
ARBs selectively inhibit the AT1 receptor, so vasoconstriction doesn’t occur and it is thought that this allows for increased blood flow to the brain and accounts for the neuroprotective effect.

Using a combination of an ARB and ACE was found to be of particular benefit perhaps because of the reduced risk of stroke and the ARB preventing vascular damage induced by beta amyloid that accumulates in the brain in Alzheimer’s disease.

The bottom line.

The most important factor here is to ensure that you keep your blood pressure in the normal range.

If you haven’t had your blood pressure checked in a while, NOW is a good time to make an appointment to see your doctor.

If you do have high blood pressure then ensure you make all the necessary lifestyle adjustments to see if you can bring it down to normal on your own.

If despite all this, your blood pressure remains elevated, talk to your doctor about which medication would be the most appropriate for you. Remember these observational studies are only suggestive that certain medications i.e. the ARBs may be of benefit in preventing the risk of Alzheimer’s and other dementias. Your doctor is in the best position to know which medication may be most suitable for your own particular needs. The main thing is to keep your blood pressure in the normal range.

Meanwhile further research will help to ascertain whether in fact the ARBs do have an advantage in helping to reduce the incidence of Alzheimer’s. Time will tell.

Do you know if your blood pressure is normal?

Refs:

Davies,N.M., Kehoe, P.G., Ben-Shlomo, Y., Martin, R.M.
Associations of Anti-Hypertensive Treatments with Azlheimer’s Disease, Vascular Dementia and other Dementias . Journal Of Alzheimer’s Disease October 2011 pg 699-708

Boston University Medical Center (2010, January 12). Angiotensin receptor blockers associated with lower risk of Alzheimer’s disease. ScienceDaily. Retrieved October 31, 2011, from http://www.sciencedaily.com¬ /releases/2010/01/100112201345.htm

We know the old adage of eating 2 fruit and 5 vegetables every day for our general health. Many of those which are highly coloured, red, yellow and green have been identified as containing high levels of phytochemicals which can have a positive impact for our heart health and brain function.

Researchers have now found that eating the white flesh of fruits appears to be protective versus stroke.
In a Dutch study published in Stroke: Journal of the American Heart Association it was noted that the incidence of stroke in those who ate more white fleshed fruits and vegetables was about half that of those who ate relatively little.

For every 25 grams per day increase in white fruit and vegetable consumption there was a 9% lower risk of stroke.

An average apple weighs around 120grams.

And before you reach for the next plate of hot chips – potatoes were classified here as a starch source.

Apples and pears provided over half the intake of white fruits eaten over the study, which ran for ten years.
What are the other white fruits and vegetable to think about?

Bananas, cauliflower, cucumber and chicory (witlof)

Over twenty thousand people contributed to the study, which took the form of food frequency questionnaires. None had any identifiable cardiovascular disease at the beginning of the study and the average age was 41 years.

Why is this relevant to brain health? Stroke is a major cause of health burden and vascular dementia is the second most common form of dementia.

An editorial published with the article cautions that this research may not be 100% reliable from its use of these type of questionnaires and also did not factor in for the variable that those eating more white fleshed fruits may have been those already leading healthier lifestyles.

Any which way, it is always going to be a good thing to include a wide variety of fruit and vegetables in your diet.

So, next time you take an apple to school for teacher, remember to pack one for yourself as well.

Ref:
Linda M. Oude Griep, W. M. Monique Verschuren, Daan Kromhout, Marga C. Ocké, Johanna M. Geleijnse. Colors of Fruit and Vegetables and 10-Year Incidence of Stroke. Stroke, 2011; DOI: 10.1161/STROKEAHA.110.611152

What is stress?

It has been defined in a number of different ways but for the purpose of this article, is taken to be: a sense of irritation, tension, nervousness, anxiety, fear or difficulty sleeping, lasting over a month as a result of problems at home, at work or health worries.

Stress is a term often used in society, but do we really understand what stress actually is and why it matters to brain health?

Should we worry about stress as a risk factor for dementia and Alzheimer’s?

Severe chronic stress is bad for our health. This is the sort of stress that keeps you awake at night with worry. This is the sort of stress that is associated with excessive release of catecholamines, the substances associated with the “flight or fight” syndrome. Here cortisol, which in normal amounts causes no problem, exerts a toxic effect on our neurons.

Studies looking at dementia risk and stress.

A high level of cortisol in the brain, by accelerating the process of biochemical and behavioural pathology, has been linked to an increased risk of dementia.

The results of a population study on a group of 1400+ women in Sweden followed for over 35 years from 1968 was published in 2010. They were aged between 38 and 60 when first recruited to the study and answered questions including one asking about psychological stress in 1968, 1974, and 1980.

Of the group, 161 women developed dementia (mostly in the form of Alzheimer’s disease). Those who had reported having repeated periods of stress in middle age were shown to have a 65% increase in their risk of dementia. In those who reported stress in all three surveys had double the risk. In this study, the timing of the stress was relevant. In other words, exposure to repeated stress in middle age appears to elevate the risk

Should this be a surprise? Maybe not. It is already known that stress has a negative impact on our health, increasing our susceptibility to an impaired immune response and an increased risk of cardiovascular disease in the form of stroke, high blood pressure and heart attack.

Previous animal studies had also previously shown an association of stress and dementia risk.

But it also needs to be put into perspective. The vast majority of women participating in the study did not develop dementia. So while stress is significant and needs to be dealt with appropriately, it is important not to stress, that being stressed will lead you to developing dementia!

In another study, the physiological changes in neurons susceptible to the effect of stress were examined were examined.
Here, researchers using rats, showed how stress led to an increase in the formation of abnormal clumps of tau protein in neurons. This led to increased cell death, particularly in the area of the brain associated with learning and memory i.e. the hippocampus and prefrontal cortex.

This builds on previous findings that stress is associated with the build up of beta amyloid, another protein associated with the pathology of Alzheimer’s disease.

The next step will now be to examine to see whether these results implicating stress as a possible trigger of neurodegenerative disease can be replicated in humans. One of the researchers Osborne Almeida, has also questioned the relationship between stress and depression. Stress has been recognised as a major risk to a person’s propensity to develop major depression. Could beta amyloid and tau proteins, by being accelerated to form under the influence of stress, be implicated in the development of this disease as well?

Stress Management: The need to manage stress levels.

The bottom line is that the effect of stress on our health and well-being should not be underestimated.

• Be aware that stress is potentially harmful to your health.
• Make sure you know what you can do and how you can mitigate the effects of stress.

This could be in the form of physical exercise, talking to a trusted friend or family member, seeking medical advice, learning meditation, practicing yoga or tai chi, deep breathing or mindfulness training.

So don’t ignore symptoms of stress either personally or in someone else. Take the necessary steps to bring your stress under control and minimise any potential risk to the health of your body and brain.

Refs:

L. Johansson, X. Guo, M. Waern, S. Ostling, D. Gustafson, C. Bengtsson, I. Skoog. Midlife psychological stress and risk of dementia: a 35-year longitudinal population study. Brain, 2010; DOI: 10.1093/brain/awq116

Ioannis Sotiropoulos, Caterina Catania, Lucilia G. Pinto, Rui Silva, G. Elizabeth Pollerberg, Akihiko Takashima, Nuno Sousa, and Osborne F. X. Almeida. Stress Acts Cumulatively to Precipitate Alzheimer’s Disease-Like Tau Pathology and Cognitive Deficits. Journal of Neuroscience, May 25, 2011; 31(21):7840-7847 DOI: 10.1523/JNEUROSCI.0730-11.2011