Genetic test could predict people at higher risk of memory problems

This recent piece of research may be of interest:

https://www.alzheimers.org.uk/site/scripts/news_article.php?newsID=2625

Memory retrieval, not storage, hinders mouse models of Alzheimer’s

I found this report on a research project very interesting:

http://www.alzforum.org/news/research-news/memory-retrieval-not-storage-hinders-mouse-models-alzheimers

All the usual caveats apply, of course  -  many years before this knowledge could lead to a treatment, probably doesn't apply to all dementia, etc. But I've always felt that S's most significant problem as the dementia progressed was retrieval of memories rather than storage. I felt many times that the memory was still in there somewhere and occasionally its retrieval could be 'triggered' by an event, what someone else said, a picture, music.....

Another study reports cognitive decline with tamoxifen

I've posted about the breast cancer drug Tamoxifen before.  More than one study has suggested that this drug may cause or contribute to cognitive decline.

These are links to earlier posts on this topic:

http://adventureswithdementia.blogspot.co.uk/2011/10/possible-causescontributory-factors-2_16.html

http://adventureswithdementia.blogspot.co.uk/2011/11/more-on-tamoxifen.html

http://adventureswithdementia.blogspot.co.uk/2012/06/tamoxifen-again.html

This link is to a recent report on research which again suggests that Tamoxifen may be responsible for cognitive decline in some women:

www.examiner.com/article/another-study-reports-cognitive-decline-with-tamoxifen

A deeply moving story

This dementia related story is becoming an online sensation and many people in the UK and beyond will be aware of it, but I didn't want anyone to miss it so here it is:

http://www.bbc.co.uk/programmes/p0223027

I don't think any further comment from me is necessary but please feel free to comment yourself if you wish.

Comments on Cameron's latest speech about dementia

As promised, some thoughts about the various points he made:

'The prime minister was speaking to an audience of 300 experts who have pledged to find a cure by 2025.'

Here again we find the all too common confusion.  Have the experts really pledged to find a cure for dementia (i.e. all forms of dementia) by 2015? This seems very unlikely since, as we have mentioned several times on the blog, dementia can be caused by a wide range of different diseases and conditions.

'He said there was a need to develop more drugs and get them to patients more quickly. For that to happen, international collaboration and more money for dementia research was needed, he said.'

It's impossible to argue, though one has to say that unless the 'new drugs' are a lot more effective than current ones they won't get us close to any 'cures'.

''He added: "Something like £50m a year is being spent on dementia research, rather than the £590m spent on cancer. It is important to see dementia as a disease and one that we need to better understand so that we can tackle it." '

Again, dementia is called a disease  -  you'd think someone would tell him, wouldn't you?  But there's no denying that much more money needs to be spent on research.  And there needs to be a broader approach so that it's possible for researchers to obtain funding for work on neglected approaches rather than chipping away at the same coal-face as every other researcher.

' "So much of this is about making sure hospitals and care homes treat people with dementia better and, absolutely crucially, that we build dementia-friendly communities where all of us try and understand better what it's like to live with dementia," he said.'

Amen to this.  But, although there is a long, long way to go, my experience is that almost wherever you go there's a growing number of people who have some understanding of dementia.

Cameron's latest speech about dementia

A previous post (which has by far the most page views on AWD) discussed the Prime Minister's useful acknowledgement that Alzheimer's is a disease:

http://adventureswithdementia.blogspot.co.uk/2013/03/cameron-its-disease.html

Now, over a year later, he has addressed the subject again:

http://www.bbc.co.uk/news/health-27912473

I want to deal with this in more detail when I have the time so I'll just point out that he unhelpfully calls dementia a disease (which it isn't  -  see: http://adventureswithdementia.blogspot.co.uk/2014/06/alzheimers-or-dementia.html)

The comments underneath the article are the usual mixture of the insightful, the ill-informed and complete tosh.

Cameron: 'It's a disease!'

An extract from yesterday's Hansard: 

Tracey Crouch (Chatham and Aylesford) (Con):
Figures published yesterday show that over the past 20 years there has been a 137% increase in the number of deaths linked to Alzheimer’s disease. Does the Prime Minister agree that if we are to stop that awful condition from afflicting more people in the future, we must invest much more in preventing it and on research in particular? Will he outline to the House what the Government are doing to help support those with dementia and those who care for them?

The Prime Minister:
My hon. Friend raises a point of concern to everyone in this House and everyone in this country, because no one knows when a relative could be afflicted by the condition. Her point is absolutely right: this is a disease and we should be thinking about it as a disease, as we do when we try to crack cancer, or heart disease, or strokes. That is why the Government are increasing the amount of money going into medical research so that we can try to prevent dementia in more cases. But there are many other things we need to do to improve the care in care homes and in hospitals and to ensure that we have more dementia-friendly communities so that we all learn how to deal with people who have dementia and how to help them lead lives that are as productive as possible.

This is very interesting.  First, Cameron is stating publicly that 'it' is a disease and comparing it with cancer heart disease and stroke.  Millions agree (the clue is in the name: Altzheimer's Disease).  But it isn't treated like these other diseases either in the way that people with the disease are cared for (their treatment is not 'free at the point of use') or in terms of the amount spent on research (the modest increase in no way reflects the scale or impact of the disease).

It will be fascinating to see whether he stands by this statement, actions speaking louder than words.

I'm inclined to think that it's just the usual PR.  As a politician he makes a fine PR man. 

But at least now these words are on record and there's something to try and hold him, and others, to.

Follow this link for a more recent comment on Cameron's views on dementia:

http://adventureswithdementia.blogspot.co.uk/2014/07/comments-on-camerons-latest-speech.html

Herpes, Alzheimer's and schizophrenia - yes!

I was reading about schizophrenia, prompted by an article about a young girl diagnosed with it.  Her hallucinations were described and I couldn't help noticing similarities between her symptoms and S's.

Further searches appeared to suggest possible links with Alzheimer's and dementia more generally.  It's clear that in schizophrenia, whilst the psychotic symptoms predominate (they're actually referred to as positive symptoms), there are also less prominent symptoms of cognitive deficits which closely resemble those of dementia. 

These include the loss of concentration skills, memory, coordinated movement and dexterity.  And these are associated with the same kind of brain shrinkage, in the same regions of the brain, as is found in patients with dementia.

The next obvious step was to google herpes and schizophrenia.  By now, I wasn't surprised to get a large number of interesting results.

Cold sore virus and schizophrenia

You really should read the article  -  it's not too long  -  but this extract is so similar to statements I've read about herpes and dementia:

"We're finding that some portion of cognitive impairment usually blamed solely on the disease of schizophrenia might actually be a combination of schizophrenia and prior exposure to herpes simplex virus 1 infection, which reproduces in the brain," says study leader David J. Schretlen, Ph.D., an associate professor in the Department of Psychiatry at Johns Hopkins University School of Medicine.

The research, described in the May Schizophrenia Research, could lead to new ways to treat or prevent the cognitive impairment that typically accompanies this mental illness, including with antiviral drugs, the scientists say.

Citation: Disabled World News (2010-05-29) - Cold sore virus may contribute to cognitive and brain abnormalities in schizophrenia: http://www.disabled-world.com/health/dermatology/herpes/herpes-schizophrenia.php#ixzz2IVFFwy6X

I need to think about all this and to do some further searching.  But clearly HV1 is an even more ubiquitous and harmful virus than most people think.

Going home

When my wife was at the lowest point in her decline last autumn, a professional arrived just at the point when she had fallen down and was either refusing or unable to get up.  She kept saying: 'I want to go home.'  'I assume this is where she lives?', he asked.  When I confirmed that it was, he nodded sagely.  I have since learned that this is a common feature in the progression of the disease.

People ask why.  Some conclude that, as so often in the case of older people with the disease (and as often in the case of older people generally) the person is harking back to their early years, safe and secure at home.  They may be.  But to me, it seems more general than that.

Everybody seems to have some concept of 'home' that may have similarities to the home they first knew but may not.  Even people who have had awful early experiences usually pick up the idea of what home is supposed to be.  We all talk of feeling 'at home' in comfortable places and a host will say 'make yourself at home'.  And we have sayings like: 'Home if where the heart is.'

It seems quite understandable to me that when someone's world is falling apart, they would like to 'go home'.

The most important point to me is that I can't remember the last time S said this.  It must have been a long time ago.

Treasuring what you've still got

Someone was worrying online about her mother who wrote down the names of people in their family and her relationship to them.

I can understand the upset when the list was first discovered, but the positive way to view it is that it's good that she can still read and write and, even better, can reason that if she writes the names down this might help her to remember them.

Personally, I don't worry too much about names. My wife knows who I am (and will probably at some stage not know). She doesn't use my name. So what? She knows who the important people in her life are when she meets them and when I talk about them. These are the things that matter. 

She's not been able to write for a long time. I tried to help her retain the skills involved for as long as possible but it got too frustrating for both of us. I'm almost certain she can't read. At all. But I don't know for sure because when I understood how awful it was for her to be 'tested' (by anybody) I stopped testing her and asking her test-like questions.

One's expectations change. But the important thing is to try and make the most of what you've got - today. You might not have it tomorrow.

The best way to look at it is not 'What have we lost?' but 'What have we still got?'

Tamoxifen again

I've blogged about the possible link between Tamoxifen and memory/dementia:
here and here.

This is a link to an interesting article on this topic:
http://www.sciencedirect.com/science/article/pii/S0091305701006566.

Another interesting article  -  see the abstract at the start:
http://www.faceblind.org/social_perception/papers/zbasseda/zbasseda-Tamoxifen.pdf

Perhaps most interestingly, Tamoxifen appears to be a drug that researchers turn to when they wish, for whatever reason, to impair the memory of mice: as this link shows  -  and it's an interesting article in its own right: 'After being given tamoxifen (perhaps best known as a breastcancer drug) for eight days, an otherwise normally developing mouse had more than 80 percent fewer new neural stem cells in its hippocampus (a structure in the brain's frontal region linked to short-term memory).' And whereabouts in the brain is Alzheimer's first detected? In the hippocampus, I believe.

More about HSV 1 and beta amyloid

This blog post is another clear explanation of the possible (likely?) link between the Herpes virus and many cases of Alzheimer's. It also clarifies the uncertainties about whether beta amyloid is a cause of, or a reaction to, the disease.

The drugs don't work

Well, not quite true but it does seem to be the case that the best known drugs used to treat dementia symptoms are pretty poor. People carry on prescribing them and consuming them because what else are they going to do?

These two examples are from the Alzheimer's Society website:

What are the benefits of cholinesterase inhibitors?

In clinical trials of all three cholinesterase inhibitors, people taking the medications performed better on memory and thinking tests than those taking a placebo, or inactive substance. The degree of benefit was small, however, and more than half of the recipients showed no improvement at all.

What are the benefits of memantine?

One clinical study showed that people taking memantine showed a small but statistically significant improvement in their mental function and ability to perform daily activities. But study participants with lowest cognitive functioning showed no improvement on either daily activities or overall function.

This kind of thing makes it all the more puzzling that there's a big campaign to encourage people to come forward and collect their diagnosis so that they can be 'helped' - presumably with these and equally pathetic drugs.

More on Tamoxifen

I've not had time yet to find the very detailed letter referred to in the previous Tamoxifen post. However I know the main problem with trying to pin down whether Tamoxifen can have adverse effects in the brain. It definitely crosses the blood/brain barrier. But the complication is that sometimes Tamoxifen acts like Oestrogen and sometimes it acts as an anti-Oestrogen. Its anti-Oestrogen manifestation is what makes it useful in relation to breast cancer, or at least in those breast cancers where Oestrogen plays a part.

It is unclear which effect Tamoxifen might have when it reaches the brain. A further complication is that it is unclear whether Oestrogen itself is beneficial or harmful to the brain; the research gives contradictory results. Unsurprisingly, in these circumstances, the small amount of research that has been done to try and determine whether Tamoxifen is good or bad for the brain is also inconclusive.

So someone like S who, on medical advice, was simultaneously taking Oestrogen (HRT) and Tamoxifen could have been adversely affected by either or both Or presumably the effects could have cancelled each other out, or they could both have had a beneficial effect. And her condition might have nothing to do with either of them!

It interests me that American scientists wanting to degrade the memories of mice used Tamoxifen to do so. These were 'transgenic mice' that had had their genes interfered with to enable this 'unusual' response to Tamoxifen. But this surely raises the possibility that humans with a particular genetic make-up could be similarly affected by Tamoxifen?

It is amazing to me that these scientists already knew about a link between Tamoxifen and memory yet no-one researching memory problems in humans seems to have made such a connection.

I will find the link to the report and post it here.

Possible causes/contributory factors 3/ TAMOXIFEN

Tamoxifen has been in use to treat breast cancer patients for several decades. Typically, it is used, either alone or in combination with chemotherapy, to treat women following surgery and appears fairly successful in preventing a recurrence of the disease.

S has not had breast cancer, but because her mother had it, and at a fairly early age, S has had regular mammograms and was invited to participate in the IBIS study designed to test whether Tamoxifen could have a protective effect against the development of breast cancer in women who might have a genetic pre-disposition towards the disease. (Actually, her mum's cancer was treated before there were tests to determine whether a particular cancer might benefit from Tamoxifen.)

S decided to participate in the trial. She was on HRT at the time, mainly because her mum was thought to be suffering from osteoporosis (though it was later decided that she wasn't). Those running the trial were aware that she was on HRT.

During the five year trial, S started to develop memory problems. She became convinced, before we ever knew anything about a possible connection, that Tamoxifen was the culprit. Shortly before the trial was due to end, she stopped taking the tablets (which might of course have been a placebo as this was a double-blind trial). Somewhere around this time she stopped the HRT also.

As things got worse, I started looking into Tamoxifen and found a surprising number of references to a possible link between Tamoxifen and memory problems. S eventually sought to discover whether she had actually been taking Tamoxifen or a Placebo and it was confirmed that she had been taking Tamoxifen.

We mentioned all this to the Professor at the memory clinic and he certainly didn't dismiss it out-of-hand (as he was quite prepared to do with other ideas).

I tried to find out from IBIS whether they had asked people on the trial if they had noticed problems with their memory (they sent out an annual questionnaire). It turned out that they had not though, interestingly, I understand that they do ask a question about this when surveying participants in the IBIS2 follow-up study testing Anastrozole, an alternative to Tamoxifen.

Eventually we were invited to meet a Professor who was one of those leading these trials. He was a very personable guy who thought S's mum might have been one of his early patients. I raised some of the things that perplexed me about the drug and its possible effects and he, very charmingly, answered them - up to a point though the answer often amounted to 'we don't really know'.

In a follow-up post I will summarise the letter he sent us following our meeting, when I have unearthed it from my increasingly chaotic 'filing system'.

Now I must go and wake S up as, for the second day running, she has slept well past noon.

At least, one way or another, she has so far avoided breast cancer. There's always a bright side if you look hard enough.

Possible causes/contributory factors 2

As I said, S has had many blood tests over the years and evidence of various different viruses has been found. Amongst these are Herpes types 1 and 2. It's common to say that type 1 affects areas above the waist and type 2 below but when you look into it they both seem able to cause problems at different places in the body, and they are implicated in lots of diseases, though this does not seem as well-known as it should be - probably because medical science, and big pharma, have very little to offer by way of eliminating them or even lessening their effects.

Some studies appear to show a link between Altzheimer's and the Herpes virus though the significance of this link is not yet clear. Presumably there could be a similar link with other kinds of dementia. Dr. Itzhaki, a British based researcher who has helped to establish the link, has concluded, "Our present data suggest that this virus is a major cause of amyloid plaques and hence probably a significant etiological factor in Alzheimer's disease. They point to the usage of antiviral agents to treat the disease and possibly of vaccination to prevent it." Sadly, it appears that further research has stalled because of lack of funding.

Possible causes/contributory factors 1

Prior to S's condition really becoming apparent, there was a decade or more when she regularly had debilitating viral infections which often kept her off work - a couple of times for long periods. During these times she had various tests when different dodgy viruses were found in her blood tests. The symptoms were sore throats, earaches, constant fatigue, headaches, muscle pain, weight gain and dizziness.

One thing she has never been tested for is Lyme disease. This is a contentious topic, it seems, but it is clear that Lyme disease - which is spread by a tick bite - can induce these kind of symptoms, sometimes many years after the initial tick bite. And the end stage of serious infection is a condition involving dementia.

At the age of 18, S spent a year doing VSO in Ethiopia where Lyme disease is endemic. During her time there she was ill with the same kind of symptoms as those mentioned above and was thought to have altitude sickness.

In the late 1980's, S spent 3 weeks in the Philipines, another area where the ticks that can cause Lyme disease are found.

We have mentioned all this to the Professor at various points during the last few years. He did not seem particularly convinced by the Lyme disease possibility but was for a long time of the view that S's problems could be the result of, or could have been exacerbated by, viral-type infection (actually, I believe that Lyme disease is caused by bacteria though the symptoms are similar to viral diseases). He actually referred us to a colleague who was supposedly investigating any possible link though this did not really get us anywhere, maybe because the guy - who seemed to have a penchant for diagnosing difficult conditions - was actually an expert in fungi, rather than viruses. He did blood tests which showed the presence of both Herpes viruses, of which more later.

So we never really got anywhere with this line of enquiry, but there remain unanswered questions about the illnesses that S kept getting, what caused them, and what the long-term effects might have been.

Interestingly, although still gets very tired at times, virtually all the other 'viral' symptoms have long since disappeared. She is seldom 'ill' now, apart from having a dodgy brain!