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

The study of neuroscience over the last three or more decades has revealed a greater understanding of how our brain works and of what causes dementia including Alzheimer’s disease. Yet the clinical diagnostic guidelines for determining what constitutes Alzheimer’s, have only just been revised after a time span of 27 years.

This update now covers the full spectrum, from the earliest preclinical stages, through mild cognitive impairment, to dementia due to Alzheimer’s pathology.

The guidelines also address for the first time the use of imaging and biochemical markers in blood and spinal fluid to help determine whether changes present are likely to be due to Alzheimer’s. As yet biochemical markers and scans are not being used in the clinical setting, they are still predominantly research tools. However this is likely to be changing in the not too distant future.

One of the key drivers to the updated guidelines has been the need to find good clinical tools to permit early and accurate diagnosis.

Previously Alzheimer’s could only be confirmed following death. Autopsy was used to show the pathological findings of amyloid plaques.
We now know that in Alzheimer’s disease, changes in the brain start developing long before any clinical symptoms are apparent and the symptoms do not always correlate to abnormal findings in the brain.

The National Institute on Aging/Alzheimer’s Association Diagnostic Guidelines for Alzheimer’s disease now covers three distinct stages of Alzheimer’s.

1 The Preclinical Stage.

These guidelines only apply currently to a research setting.
In the preclinical stage, brain changes are starting to develop, including accumulation of amyloid and some other nerve cell changes. Significant clinical symptoms are not apparent at this stage. PET scan and CSF analysis may detect the amyloid build up in some people. It remains unknown what the risk of progression of to Alzheimer’s is from this. There is much research continuing into the potential use of biomarkers in a clinical setting.

2 Mild Cognitive Impairment.

These guidelines are also mostly for research. Here a person is recognised to be suffering from memory problems but not in such a way to be impairing their daily functioning.
Not everyone with MCI will progress to full blown Alzheimer’s disease. The use of biomarkers here, is looking for evidence of increased tau protein or decreased levels of beta amyloid in the CSF, reduced glucose uptake in the brain (shown on PET scan) and atrophy of certain parts of the brain (using MRI scans)

3 Alzheimer’s dementia.

Here the clinical manifestations include (in addition to memory loss,) decline in word finding, visuo-spatial difficulty and impaired reasoning or judgement (higher levels of cognition).
Biomarker tested here can be used to increase or decrease the level of certainty about a diagnosis and to differentiate the dementia of Alzheimer’s from other forms of dementia.

This new framework will allow for new findings to be incorporated as discovered. So fortunately, we are unlikely to have to wait for another 27 years before any further revision occurs.

Ref:
NIH/National Institute on Ageing. April 19, 2011 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Are there some things, which really get up your nose?

Well this may be one thing you do want to put up there: a nasal spray capable of protecting your brain from Alzheimer’s disease or stroke.

And before you dismiss that notion as being ridiculous and from “la-la land”, it appears that researchers from Tel Aviv University may be onto something completely novel; a way of effectively preventing and treating Alzheimer’s disease delivering medication via a nasal spray.

This is a story reminiscent of the story of Viagra. The treatment for erectile dysfunction started life as a medication being developed for men with chest pain.
In this case the nasal spray was being developed as a treatment for influenza. The medical scientists were looking to induce an immune response vs. influenza and what they found was that the vaccine, caused the body to activate part of its defence mechanism against viral and other invaders, called macrophages. These macrophages act as large vacuum cleaners gobbling up unwanted proteins such as amyloid from the brain’s blood vessels. Amyloid can build up in the brain and is a pathological finding commonly found in the brain of people with Alzheimer’s disease. In animal studies, once these amyloid proteins had been cleared, then further damage to the brain could be prevented and existing damage repaired.

This means that it may be possible to repair the damage to a brain from a previous stroke and to be able to effectively treat people already experiencing symptoms associated with Alzheimer’s disease.

Previous studies into Alzheimer’s disease have looked at using an immune mediated approach using anti-inflammatory medications and steroids.

Here the immune response being induced is preventing small bleeds causing stroke, which can cause permanent brain damage and contribute to vascular dementia.

The next stage is to look at clinical trials.

So far the animal studies have shown no toxic side effects and fMRI scans on the mice confirmed the effectiveness of the vaccine in returning those mice with cognitive impairment to normal behaviour.

If the drug is found to produce the same effect in humans, this means there may be a simple way of treating up to 80% of those with Alzheimer’s dementia.

Wow, the findings from this study imply we could be looking at a possible breakthrough for a vaccine to guard against and an effective treatment for Alzheimer’s.
Something simple, hopefully inexpensive and literally brain saving.

One small spray for your brain, one giant water cannon of hope for many minds.

Ref: Dr D. Frankel. Tel Aviv Department of Neurobiology Press release

As a baby boomer with a number of baby boomer friends, there have been a couple of questions which come up regularly when we ladies are discussing menopause.

Does HRT (hormone replacement therapy) help preserve your memory and is it safe to take it for that?

Menopause is that wonderful time in a woman’s life where the monthly reminder of periods gradually fades away. This in itself is not usually an issue for most women.
What can be an issue though, is the huge array of associated, assorted symptoms that can accompany that phase.

One of the symptoms not commonly mentioned in the text-books or Doctor’s office, but one not infrequently discussed in our girls talks, is the issue of memory. In an unkind reminder of “pregnancy brain” what we now have raising it’s ugly head is “menopause brain”.
Yes, we seem to be “losing it”. Forgetting appointments, misplacing everything from the car keys to the occasional child, and stressing that not only are now entering that new phase of maturity called “middle age” we also think we might well be losing our mind at the same time.

By the time we reach our late forties and early fifties, that creeping awareness of one’s own mortality starts to develop. We notice our parents are ageing, sometimes becoming very sick or dying. Some of those parents may develop Alzheimer’s disease or dementia, and the sudden emergence of our own memory’s shortgivings can lead us to worry that we too may be at risk.

Moreover, it is known that people with Alzheimer’s and their caregivers are more likely to be women.
Maria Shriver brought home that message very clearly in her report “Women- the face of Alzheimer’s” last year.

So should we be using HRT to help save our memories?
How long should we take it for?
Does it actually make any difference?

Professor Andrew Kaunitz nicely answered these questions in an article from the Department of Obstetrics and Gynaecology, University of Florida College of Medicine.

He writes about a “critical window” of opportunity to use HRT.

In peri menopause, (the time leading up to periods actually finishing) or early menopause, using HRT is associated with a reduced risk of dementia.

However, women who start using HRT in later life actually gain no benefit and may in fact be doing harm.

A long-term cohort study from California published their findings late last year.
In this study, menopausal women aged between 40 and 55 and free of dementia, were between the years of 1963 and 1974 asked whether of not they used HRT. This was determined as being “mid life use”.

Women were again assessed some twenty five to thirty years after the mid life assessment, to see if they were using HRT. If so, they were counted as “late life” users.

Interestingly, what the group found was that those women who had only used HRT in the “mid life” had the lowest prevalence of dementia.
Those who had only used it in “later life” had the highest prevalence of dementia.

Those who had started in midlife and essentially just carried on had a prevalence similar to those women who had never used HRT at all.

Professor Kaunitz says he now advises his clients in the peri menopausal and early menopause that HRT may lower their future risk of dementia with the aim to gradually taper the dose over time and to either eventually discontinue the treatment entirely or suggest they remain on a very low dose. The total length of use also being determined by a number of other individual factors.

Meanwhile, perhaps we should also being looking to see how much relief HRT gives women afflicted by “menopausal brain”. The answer to that question may help women to then decide whether they want to use HRT either as a potential risk modifying agent of dementia, or purely for symptom relief of the “mid life brain”.

Ref:
Whitmer RA, Quesenberry CP, Zhou J, Yaffe K. Timing of hormone therapy and dementia: The critical window theory revisited. Ann Neuro. 2010 Nov 12

Are you addicted to fast food?

Do you crave that next slice of pizza or double beef burger with bacon?
Is your mouth watering at the thought of chicken and chips?

We know that eating too much fat, especially the bad fats such as trans fats and excess cholesterol, is bad for our hearts and our health.
Too much fat in the form of cholesterol is also really bad for our brain.

But surely when it comes to food choices it just boils down to personal taste, convenience, and availability doesn’t it?

Maybe not.

It turns out that many of us have a “fatty” or “salt” tooth rather than a “sweet” one.

Eating a high fat diet over a period of time has been shown to induce irreversible changes in rat studies in relation to the “pleasure centres” of the brain.

These are the same reward or pleasure centres as activated by heroin and cocaine.

So yes, it seems that we can indeed become addicted to fatty foods.

Back to those rats and their high fat diet. Over a six month period, the genes associated with reward were found to be altered, leading to the animals then craving those particular types of food when no longer available.

Which means that if you are trying to lose weight, but have previously being eating a diet high in fat, it is going to be much harder to say “no” to that temptation, next time it is wafted in front of your nose.

This could be why some people find it so hard when trying to lose weight to adhere to healthier eating in the longer term.

Our brain makes its own cholesterol that it uses to form synapses and brain cell membranes. But if our diet incorporates a high level of excess fat over a period of time, this leads to brain damage.

Rats fed excess fat in their diets over a 5 month period produced changes in their brains resembling Alzheimer’s pathology, with the formation of amyloid plaques and neurofibrillary tangles. They also showed evidence of memory impairment, loss of neurons, micro bleeds into the brain and inflammation.

Alzheimer’s is a complex neurological condition, and while cholesterol on its own is not responsible for causing it, it is certainly a contributing factor.

A second study gave rats a high fat, low Omega-3 diet. Omega-3s are essential fatty acids that we have to obtain from our food, as our body does not produce them. They are found in fish, meat, eggs and walnuts. Omega 3s are essential for normal brain function as they form part of the cell membrane around each neuron and help to maintain a healthy brain and normal cognition.

This combination diet led to brains developing x8.7 the amount of amyloid and x1.5 the amount of tau protein build up compared to controls.

So if you have that fat addiction, how can you resist that slice of oh-so-gooey and delicious looking chocolate mud cake?
And how about those piping hot chips sprinkled with salt?
Perhaps understanding that it is an addiction will help those affected to try and tackle the issue differently.

Following on from this research my question now is: what effect is this chronic high fat diet having on our kids’ brains?

Are we setting our children up for a lifetime of difficulty in weight control and contributing to their risk of developing cognitive problems or neurodegenerative disease in the future?

What are your thoughts?

Refs:
Society for Neuroscience (2011, January 19). Long-term, high-fat diet alters mice brains: Brain changes may contribute to cycles of weight gain. ScienceDaily. Retrieved January 20, 2011, from http://www.sciencedaily.com¬ /releases/2010/11/101115112727.htm

Université Laval (2008, October 31). High-fat Diet Could Promote Development Of Alzheimer’s Disease. ScienceDaily. Retrieved January 20, 2011, from http://www.sciencedaily.com¬ /releases/2008/10/081028103107.htm

Celine Ullrich, Michael Pirchl, Christian Humpel. Hypercholesterolemia in rats impairs the cholinergic system and leads to memory deficits. Molecular and Cellular Neuroscience, 2010; 45 (4): 408 DOI: 10.1016/j.mcn.2010.08.001