Herpes simplex virus type 1 (HSV1) a cause of cognitive impairment?

[adkline]

Genetics of "late-onset" Alzheimer's disease and the immune system

Dear stanleypj - I worked on Alzheimer's for over a decade. One of my last conversations in the field was with Ruth Itzhaki!

My own specialisation was in genetics. The last couple of years have brought huge amounts of new data, mostly thanks to Prof. Julie William's (Cardiff University) and Prof. John Hardy (UCL). Of the ten or so new "risk factor" genes that have been linked to Alzheimer's disease, many have roles in inflammation and immunity. I will post a link to a recent (free) independent article on your blog.

This area is underfunded principally because almost every research dollar has been spent investigating the amyloid hypothesis. This being that accumulation in the brain of a small protein fragment (known as the amyloid-beta peptide) causes the disease.

An amyloid hypothesist would argue that the only role of the immune system in Alzheimer's is to mediate removal of amyloid from the brain. This is hypothetically what goes wrong in disease. Sadly none of the anti-amyloid drugs have proven sufficiently successful to meet regulatory approval standards.

My own personal opinion is that the long-standing focus of the field on amyloid has been a triumph of politics over science. A broader approach would definitely be beneficial at this point.

 

[stanleypj]

Dear stanleypj - I worked on Alzheimer's for over a decade. One of my last conversations in the field was with Ruth Itzhaki!

My own specialisation was in genetics. The last couple of years have brought huge amounts of new data, mostly thanks to Prof. Julie William's (Cardiff University) and Prof. John Hardy (UCL). Of the ten or so new "risk factor" genes that have been linked to Alzheimer's disease, many have roles in inflammation and immunity. I will post a link to a recent (free) independent article on your blog.

This area is underfunded principally because almost every research dollar has been spent investigating the amyloid hypothesis. This being that accumulation in the brain of a small protein fragment (known as the amyloid-beta peptide) causes the disease.

An amyloid hypothesist would argue that the only role of the immune system in Alzheimer's is to mediate removal of amyloid from the brain. This is hypothetically what goes wrong in disease. Sadly none of the anti-amyloid drugs have proven sufficiently successful to meet regulatory approval standards.

My own personal opinion is that the long-standing focus of the field on amyloid has been a triumph of politics over science. A broader approach would definitely be beneficial at this point.

I'm very grateful to you. As a non-scientist with no medical training, it seems obvious to me that that the focus on amyloid, indeed the very common assertion that it is 'the cause', is a disaster in terms of finding out what will actually help people who are suffering the ravages of a very cruel disease.

I see you are a new member, so may I welcome you to the site and hope that you will post regularly and give us the benefit of your very relevant experience.

 

[stanleypj]

May I add my anecdote please?

A rather odd coincidence (we were told coincidence ) happened between my mum and her sister some 7/8 years ago. My mum and I went to visit her sister for a couple of days and approximately 5 days later they both came down with shingles. They both suffered the after effects for over a year and my mum's sister developed dementia thereafter. My mum has followed suit, although she is not yet at such an advanced stage.

For several years I blamed myself for 'giving' them both shingles and causing my aunt's demise as I had been in contact with chicken pox through school at the time (I am a teacher). Although every doctor I have asked has re-assured me, I still wonder about it all. It just seems very odd.

Angela

Very interesting starryuk. May I ask what kind of dementia your mum and her sister have been diagnosed with? Herpes zoster, the virus that causes shingles, is different from herpes simplex (HSV1) but has been linked to vascular dementia.

Whatever, as I'm sure you know, no-one can really be to blame, but it's an understandable feeling.

 

[adkline]

Amyloid and causes of Alzheimer's disease

It seems obvious to me that that the focus on amyloid, indeed the very common assertion that it is 'the cause', is a disaster in terms of finding out what will actually help people who are suffering the ravages of a very cruel disease.

Dear stanleypj - thanks for the welcome. I hope to be able to post often. Communication between the scientific classes and those on-the-ground who actually deal with the disease on a daily basis is often pretty poor.

The amyloid question is a very, very complex one. Everything has been based on the 1% of patients who develop early-onset Alzheimer's disease because of a familial genetic mutation (i.e., one of their parents also had/has the illness at a relatively young age). It is assumed that the 99% who develop sporadic disease, which strikes later in life, fundamentally suffer from the same problem. This has always been a somewhat simplified view.

Diabetes is quite a good analogy. There are two forms of diabetes - type 1 and type 2. The former is often inherited and hits very young. It is caused by a failure of the pancreas to make insulin. The latter occurs when we eat too much and don't exercise enough. There's plenty of insulin floating around in type 2 diabetes, but it is less effective because of high dietary sugar intake.

The funny thing is, both types of diabetes have very similar symptoms (abnormally high blood sugar with blood vessel and nerve problems). Treatment is very different, however. For type 1, insulin injections are prescribed. For type 2, dietary modification with supportive drugs is recommended.

Alzheimer's disease could well be very similar. Amyloid is generally found in the brain of all sufferers. It undoubtedly causes inherited, familial Alzheimer's disease without much influence from lifestyle factors. The sporadic disease that most of us know is much more complex. It is likely influenced by infections, poor diet, blood vessel disease and many other factors. Consequently, the most effective anti-amyloid drug trialled to date (solanezumab, Eli Lilly) was less potent than Aricept. A very, very disappointing result for everyone.

I hope for two things to come out of this failure:
(1) Eventually we will get safe, preventative anti-amyloid medicines. These may need to be taken for over a decade before the disease fully develops, but they may stop those most at-risk from developing the disease.
(2) The field shrugs off its bias and focuses on other solutions to help those already with the illness.

Needless to say we seem be to be doing much better at (1) than we are at (2)

 

[stanleypj]

Thanks for another a very helpful post. I find the diabetes analogy very interesting.

My wife (aged 63) has young onset AD but apparently no familial cause. In addition it took a leading expert and his team 12 years (!) to come up with a diagnosis after intensive investigation (including three different scans. For ten to fifteen years prior to any dementia symptoms she had more or less continuous viral infections with debilitating ME type symptoms and at different times tested positive for many of the viruses (and all those that have been linked in any way with dementia).

The situation is so complex with so many different types of dementia and probably as many patterns of progression as there are sufferers. It's no wonder that so little progress is made. But all the more reason for trying to ensure that all possibilities are fully explored.

 

[adkline]

Diversity of AD

My wife (aged 63) has young onset AD but apparently no familial cause. In addition it took a leading expert and his team 12 years (!) to come up with a diagnosis after intensive investigation (including three different scans.

I sympathise whole-heartedly with your very difficult situation. It sounds to me like your wife is right on the cusp of what would classically be considered Alzheimer's disease. I would assume that she has had several of what are termed "reference matched" MRI scans? This is where damage to the nervous tissue is tracked over time. If damage to the hippocampus (critical for memory formation) is higher than expected over a prolonged interval then Alzheimer's disease is generally the diagnosis. Boy is it a tricky diagnosis to make though.

Fingering sequential infections as partly responsible may well be accurate in your wife's case. Even if she doesn't have a classical familial gene mutation there are other genetic influences that cause disease in some patients. The latest, most interesting finding from Prof. John Hardy at UCL (identifying the gene TREM2) points clearly towards infection/inflammation.

It is indeed sad that so few scientists are working on exploring these mechanisms from a non-amyloid perspective.

 

[Duffer]

Dad's improvement after antibiotics for whitloes

Hi, I have other posts on this forum as my dad had a massive improvement in his dementia symptoms after being given flucloxacillin for whitloes.
Dad has been in a CH specialising in Dementia for the past 4 months after being dignosed with Vascular Dementia and being in hospital for 2 months.
It may be pure coincidence that his symptoms were improved 95% after being prescribed the antibiotics. All I know is that, for the time being I have my dad back. Dad has even been able to describe what it felt like while he was I'll - he says it was like he was two separate people and only able 'to come back' when the two parts joined up again. He has regained some of his memory but still has a chunk of about 40 years missing. He is however, aware that he is missing the chunk of memory, and is aware enough that he knows he is relearning some of the memory from photos and cine film.
He shocked me last week by asking to become an organ doner so that research might be done on his brain after his death.
His improvement is starting to decline and I would say he has slipped down to 75% improvement but it's still miraculous for me to have him back that much.
I am not for one second saying that this might be a cure but what I am trying to find out is whether some 'infections' are being misdiagnosed as dementia when they may be ways of improving the 'dementia like' symptoms.
if anybody can give me a link to some research being done then please do so.

I sympathise whole-heartedly with your very difficult situation. It sounds to me like your wife is right on the cusp of what would classically be considered Alzheimer's disease. I would assume that she has had several of what are termed "reference matched" MRI scans? This is where damage to the nervous tissue is tracked over time. If damage to the hippocampus (critical for memory formation) is higher than expected over a prolonged interval then Alzheimer's disease is generally the diagnosis. Boy is it a tricky diagnosis to make though.

Fingering sequential infections as partly responsible may well be accurate in your wife's case. Even if she doesn't have a classical familial gene mutation there are other genetic influences that cause disease in some patients. The latest, most interesting finding from Prof. John Hardy at UCL (identifying the gene TREM2) points clearly towards infection/inflammation.

It is indeed sad that so few scientists are working on exploring these mechanisms from a non-amyloid perspective.

 

[stanleypj]

I hope someone will come along with some useful info for you Duffer. I think it's great that you have posted so much about your dad's improvement. Even though you've expressed all your reservations and qualifications you've encountered some scepticism, I think it's fair to say.

I sometimes wonder if many are so used to the negativity and fatalism attached to the disease that they are incapable of accepting that any improvement or regained awareness is possible.

As you say, it is just possible that your dad does not have any recognised form of the disease but has been misdiagnosed.

 

[adkline]

Infection and dementia

if anybody can give me a link to some research being done then please do so.

The person I have heard talk most convincingly on this topic is Prof. Hugh Perry of the University of Southampton. I can't post a link here as I'm a new member. However, if you Google "Hugh Perry Southampton", his is the first page to come up. Click the publications tab and there's a list of his recent articles.

They are all, I am afraid, in technical language. If you have an questions on the content though I'll do my best.

When I heard him speak he discussed urinary infections and rapid (almost overnight) worsening of dementia patients' symptoms. This anecdotal connection is also recognised by the Alzheimer's Society (factsheet 528). There is criminally little research being done into this phenomenon, however.

 

[stanleypj]

The person I have heard talk most convincingly on this topic is Prof. Hugh Perry of the University of Southampton. I can't post a link here as I'm a new member. However, if you Google "Hugh Perry Southampton", his is the first page to come up. Click the publications tab and there's a list of his recent articles.

They are all, I am afraid, in technical language. If you have an questions on the content though I'll do my best.

When I heard him speak he discussed urinary infections and rapid (almost overnight) worsening of dementia patients' symptoms. This anecdotal connection is also recognised by the Alzheimer's Society (factsheet 528). There is criminally little research being done into this phenomenon, however.

Absolutely. UTI's are discussed on TP on a very regular basis. Often carers only discover that this may be the reason for a dramatic downturn when they post a question on here. The professionals supposedly caring for the person experiencing the crisis sometimes have to be asked to test for a UTI. Criminally poor care as well as criminally little research.

 

[christy]

Herpes and AD

Hello, I'm German, 59 years old. A long time ago I read with great interest from the research of Dr. Itzhaki Manchester UK and now also the posts here about Herpes and AD. Please excuse my insufficient knowledge of English.
For me, the diagnostics showed in 5/2011 positive markers in CSF and corresponding changes in MRI (brain atrophy).
Therefore already incapacity to work.
For more than 30 years I've also recurrent Herpes type 1 + 2. Since the frequency of outbreaks extremely increased I got VALACICLOVIR as a suppressvie therapy: Initial 3 months 2 x 500 mg. Continue to 500 mg daily as a maintenance dose.
Among them no more Herpes and it disappeared the AD symptoms, even so I'm now back to work!!!!
According to my personal experience I suspect also a link between HSV and AD.
Best regards, christy

 

[Sue J]

Hello, I'm German, 59 years old. A long time ago I read with great interest from the research of Dr. Itzhaki Manchester UK and now also the posts here about Herpes and AD. Please excuse my insufficient knowledge of English.
For me, the diagnostics showed in 5/2011 positive markers in CSF and corresponding changes in MRI (brain atrophy).
Therefore already incapacity to work.
For more than 30 years I've also recurrent Herpes type 1 + 2. Since the frequency of outbreaks extremely increased I got VALACICLOVIR as a suppressvie therapy: Initial 3 months 2 x 500 mg. Continue to 500 mg daily as a maintenance dose.
Among them no more Herpes and it disappeared the AD symptoms, even so I'm now back to work!!!!
According to my personal experience I suspect also a link between HSV and AD.
Best regards, christy

Dear Christy

How wonderful, thank you so much for posting this

Beste grüssen ( see my German's probably not good anymore! your English is fine)
Sue

 

[stanleypj]

Hello, I'm German, 59 years old. A long time ago I read with great interest from the research of Dr. Itzhaki Manchester UK and now also the posts here about Herpes and AD. Please excuse my insufficient knowledge of English.
For me, the diagnostics showed in 5/2011 positive markers in CSF and corresponding changes in MRI (brain atrophy).
Therefore already incapacity to work.
For more than 30 years I've also recurrent Herpes type 1 + 2. Since the frequency of outbreaks extremely increased I got VALACICLOVIR as a suppressvie therapy: Initial 3 months 2 x 500 mg. Continue to 500 mg daily as a maintenance dose.
Among them no more Herpes and it disappeared the AD symptoms, even so I'm now back to work!!!!
According to my personal experience I suspect also a link between HSV and AD.
Best regards, christy

Thank you Christy. This is very interesting. What do your doctors say?

 

[BR_ANA]

Christy
welcome to TP.

 

[starryuk]

this is so interesting-Mum had about 6yrs ago the most terrible shingles which covered her face and head all over-She looked like she had been in a major car crash!Shingles is caused by the cold sore virus or is in the same group(i've no medical knowlege) After mum had recovered from the shingles- over time , she became more forgetful and confused.We asked the GP could shingles have contributed to mum's state of mind and he pooh- poohed the suggestion saying there was no link-but after reading this I feel that there may well be.Has anyone else experienced anything like this after face/head shingles

Both my mum and her sister developed shingles within days of each other. ( I sort of got the blame as I had lunch with them both having been in contact with chicken pox at school). All doctors have consistently said impossible. My aunt was very ill and went on to develop dementia of some kind.
Although we are consistently being told there is/was no connection, we can't help feeling there must be.

 

[stanleypj]

The virus that causes shingles - herpes zoster - is in the same family as those that cause cold sores and genital sores. I am not aware of any research linking it to dementia.

It is striking though how many of the herpes viruses have been linked to major diseases.

 

[SueENG]

this is so interesting-Mum had about 6yrs ago the most terrible shingles which covered her face and head all over-She looked like she had been in a major car crash!Shingles is caused by the cold sore virus or is in the same group(i've no medical knowlege) After mum had recovered from the shingles- over time , she became more forgetful and confused.We asked the GP could shingles have contributed to mum's state of mind and he pooh- poohed the suggestion saying there was no link-but after reading this I feel that there may well be.Has anyone else experienced anything like this after face/head shingles

Don't you just love it when Doctors undermine what you have to say, as if they are experts in Alzheimers! Mum wasn't one for cold sores but has had shingles a couple of times.

 

[SueENG]

Shingles, H Pylorie, sticky blood syndrome do all trigger inflammatory response?

Is it the inflammation of these conditions that cause toxic build up and plaques to form in the brain? Is this similar to toxic build up in the joints as in arthritis. Could dementia be a form of brain arthritis?

 

[Sue J]

Is it the inflammation of these conditions that cause toxic build up and plaques to form in the brain? Is this similar to toxic build up in the joints as in arthritis. Could dementia be a form of brain arthritis?

It is my experience that I have inflammatory flare ups in my arthritic joints ( although not all my joints are are) when my brain symptoms are at their worst, linked to my menstrual cycle. It is my belief it is auto immune in nature. My brain is inflamed, like being on fire, is what I kept telling the Drs - one did believe me but she was up against a neurologist who didn't even know how to talk to a patient to find out anything about my symptoms and dismissed me as needing 'psychiatric care'. Most of all I needed someone to listen to me and believe me.

I have become a disabled person where I wasn't before.

 

[stanleypj]

It is my experience that I have inflammatory flare ups in my arthritic joints ( although not all my joints are are) when my brain symptoms are at their worst, linked to my menstrual cycle. It is my belief it is auto immune in nature. My brain is inflamed, like being on fire, is what I kept telling the Drs - one did believe me but she was up against a neurologist who didn't even know how to talk to a patient to find out anything about my symptoms and dismissed me as needing 'psychiatric care'. Most of all I needed someone to listen to me and believe me.

I have become a disabled person where I wasn't before.

Sue, I think the best doctors do listen to what people are telling them. Our experience of neurologists has been very unfortunate though - the ones we've met have been too interested in the brain and ignored the person.

The leading expert we had the good fortune to be seen by for about twelve years once wrote in a letter to another professional 'I am very reluctant to discount what a patient is telling me'. Perhaps all doctors shound have this on a poster to remind them.

It must be very frustrating for you, particularly in view of your background, that they won't listen.

I don't think you're alone in believing that there could be a link between some forms of arthritis and some types of cognitive impairment.

I hope you will keep telling them what you think, even when they don't appear to be listening.