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Contents

Genetic Advances in understanding the cause of frontotemporal dementia - Huw Morris
My Wife Maura - Barry Rowley
Report from the AGM in Nottingham - Penelope Roques and Carol Jennings
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Genetic advances in understanding the cause of  fronto-temporal dementia.

The genes that we inherit contain the instructions which determine the building of all of our proteins. Mike Hutton and his colleagues in the Mayo Clinic in Jacksonville, Florida together with a research team from Manchester, Washington and Holland determined that an inherited abnormality (“mutation”) in the tau gene, which makes tau protein, is sufficient to cause FTD in later life.   While this finding is extremely important mutations of this type are likely to account for only a small percentage of patients with FTD. This knowledge gives us the first clues as to how tau protein can build up in nerve cells and shows that the build up of tau protein is a fundamental cause of the whole disease. If treatments were developed which could stop the abnormal build-up of tau, or preserve its’ normal function, then these would almost certainly slow down or stop the progression of the disease process. Interestingly tau protein also builds up in the nerve cells of patients with Alzheimer’s disease, progressive supranuclear palsy (PSP) and cortico-basal degeneration (CBD) although primary mutations in the tau gene have not been described so far in these conditions.

This new information from  FTD indicates that tau may be a very important cause of nerve cell damage in these other conditions - equally, treatments may be developed that are effective in all of the conditions. Does this mean that fronto-temporal dementia runs in the family? Most later onset degenerative neurological conditions like Parkinson’s disease, Alzheimer’s disease and FTD appear to exist in familial and ordinary sporadic forms. Familial forms seem to occur in between 1 in 10 and 1 in 20 cases and studies of families with these conditions can lead to very important information about the disease for all of the sufferers.  FTD seems to follow a similar pattern; if only one person in the family has the condition, as happens 19/20 times then it is very unlikely that anyone else will be affected, if several people in the family have the condition then it may be that further members of the family will be “at risk” - and this should be discussed with your doctor or the Candid group. Is there a test which can predict who is going to suffer from FTD? As mentioned above, the vast majority of cases of FTD are sporadic and there is no test which can predict who in the population will be affected.  Similarly, mutations in the tau gene account for only a small proportion of families with FTD so unless a family has been identified as having a tau mutation then there are no available tests.

How close are new treatments?
Treatments which control the symptoms of neurodegenerative diseases, with the exception of Parkinson’s disease have so far been disappointing.  Attention is now turning to so called “disease modifying” treatments which could halt or slow down the progression of the disease by preventing premature nerve cell damage or death. The recent research into tau genetics makes it possible to make test tube and animal models of these diseases.  Understanding the way in which tau protein damages cells, which is a rapidly unravelling process, allows rational new disease modifying treatments to be designed.  Fortunately it is beginning to appear that although the symptoms and problems faced by sufferers and carers may be very different similar types of cell damage do occur in FTD, PSP, CBD and Alzheimer’s disease so the numbers of patients that might be involved in new treatments is large.  In other words the same treatment might be used for all of these conditions.  Prof John Hardy, working on both genetics and disease models in the Mayo Clinic, Jacksonville believes that new treatments based on this information will be developed within the next five years but the pace of these discoveries is often difficult to predict.

What is wrong with the tau protein and why can’t it be repaired?
The tau protein seems to normally function to stabilise connection pipes called microtubules within nerve cells.  Part of the tau protein sticks to the microtubules and part sticks out into the cell’s interior.  All the problems described with tau protein so far seem to involve failure of the binding of tau to microtubules.  This  may either lead to the build up of toxic amounts of tau in nerve cells, perhaps as clumps of protein called neurofibrillary tangles or it may destabilise the microtubules preventing the transport of essential chemicals within the nerve cells.  There is currently no way to alter the abnormal tau sequence within nerve cells to restore its’ normal function and it is likely that this will remain very difficult to accomplish.  It’s more likely that treatment approaches would involve giving a new chemical which could compensate for the loss of tau function or prevent tau’s toxic effect. This is a very rapidly developing area which is producing great scientific interest and most importantly improving our understanding of these disease which must bring new treatments closer.  None of the work would be possible without the help and co-operation of patients and their families and we are very grateful to all of you who have helped by donating a blood sample for anonymous DNA analysis.

We are greatly indebted to Huw Morris for very kindly writing this article for the Pick’s Disease Support Group.
Neurogenetics, Institute of Neurology, Queen Square, London WC1N 3BG
 

Would you like to know more about the rare dementias?    Do you know about the concerns of carers?    What are the needs of the younger person with dementia?    To find out the answers you need    The Unusual Dementias Roadshow    On invitation, we could come to you area (within the UK). For more information contact Penelope or Carol (see contact details)

My Wife Maura

In May 1997 my wife Maura woke me early screaming my cars been stolen, my cars been stolen. She had a rally green MG Metro, which she used to get to work, The car, her pride and joy was gone. Maura worked as a care assistant in a nursing home and needed a car to get to work, she went to work that day and left me to sort the stolen car. I replaced her car with an old banger and waited for the insurance payout. Then in July she was driving along a small road in our town. A stolen car turned sharp right and crashed into her car. My wife and daughter Katie were taken to hospital with whiplash, but not detained. Shortly after this, I began to notice that Maura had begun to slur on the odd word, she has a large tongue and I thought it was something to do with that or her bridge. The accident almost forgotten life went on, more words became slurred and I began to think she was drinking during the day. Maura was a very good darts player, captained a man's darts team on Friday nights, and beat male darts players regularly. She began to get moody about this time, more so than usual. She went to the Doctors and began taking HRT. She was 47 and the change of life had started. HRT made her worse so she stopped taking it. We always walked to darts and sometimes she would cross the road as soon as we left the house and wouldn't walk with me. Fine I thought walk by yourself; I could walk very fast and would get to the club before her. I'd get the drinks in and wait for her to arrive. This began to happen more often and was really beginning to annoy me. She started walking home very slowly as well, knowing quite well that she was annoying me. She also began to sit at the bottom of the stairs by the front door at 7o'clock, waiting to out even though it was too early.

We went on holiday in August to Gran Canaria and had a good time. Her slurring continued not to an embarrassing degree, but noticeable. Back home and by Christmas it was pretty bad, especially after a drink. In January Maura and our daughter Katie went to watch Tottenham and Barnsley in an FA cup match, a chore for Katie as we both have season tickets at West Ham. On the way home Maura slipped up the stairs on the underground and twisted her leg. From this she developed a limp, but would not stop wearing high-heeled boots, she began to want taxis to and from darts. We used to play matches on Friday. Sunday nights we practised and invariably played doubles. She began to hate being on the losing side and would want to leave early if her partner wasn't good enough. The Sunday nights gradually died off and we stayed in. It was about this time that I stopped eating at home. Dinner was ready to be served at 5 o'clock. I have very difficult job and couldn't always get home for five. Sometimes Maura and Katie would have eaten and my dinner would be in the oven, most times everybody would wait until I got in and we would eat the dinner that had been kept warm in the oven and overcooked. Sometimes when I was oft work she would begin to cook dinner at 2 o'clock and we would eat just after 3o'clock. She also began to cook things in the wrong order. I couldn't put up with the race to get home so I told her I had to work when I got in and not to cook for me.

Her slurring got worse and the limp more pronounced. Maura went to the Doctors quite a lot now, always about her leg, I would ask what he said about her speech, nothing was the reply. The next time she went Katie went with her to explain what her problems were. The Doctor was very abrupt and told Katie to be quiet and let her mother do the talking. Katie tried to explain that her mum couldn't talk; but was ignored. They left the surgery near to tears, but with an appointment for leg X-rays, nothing for the speech. Its was now March 1998 and I was worried, her speech was getting really bad, we began to look for a reason, our son found a case in a magazine of woman who had suffered a whiplash injury and developed a condition called dystonia torticollis. This injury caused speech and balance problems but could be cured by a simple operation. I made an appointment with a female Doctor in the hope of a more sympathetic approach; I showed the Doctor the article cut from the magazine. She was very sceptical that it could be torticollis, I think she knew even then that it was far more serious.

Maura was referred to a consultant at Kettering Hospital, who couldn't decide what was wrong with her. A series of tests began, including CT and MRI scans. April and into May and her speech was really bad and I was very worried, Maura was unconcerned that she couldn't speak and was only concerned with her leg, which she said was cold. I took her back to the GP; it was arranged to admit her to the neurological ward at Kettering General Hospital for tests. We didn't know and the GP who referred her didn't know that the Neurologist was on holiday. We had a nightmare three days with her in hospital, begging and crying to go home. We were about to give in and take her home, when the Neurologist returned. An examination followed, the Doctor was seeing Maura at her worst; slack jawed, limping and very emotional. I heard him say to his assistant Pseudo Bells Palsy. He wanted to take Maura into the Leicester Royal Infirmary to do further tests.

We were due to go holiday in June, he said don't cancel it, we will arrange to bring her in later. I looked up Bells Palsy and knew things were bad. June, we went on holiday to Gran Canaria again, just as the World Cup was starting. Maura couldn't speak in sentences now but knew all the footballers names and in the bar at night she point them out on TV and name them. Going out at night got earlier and earlier.  We would be out before most of the bars opened and back to our apartment about ten, most nights without dinner. Our arrangement has always been that I pay for the drinks and she pays for dinner now I was having to get her back to the apartment, then go out and get Pizzas.

Holiday over and back home, Maura had been studying for an NVQ in caring, she completed it and passed. She continued to work, although she limped badly and couldn't talk. She went into Leicester Hospital in August and was in for 4 days of tests. The neurologist Dr Lawden said at the end, he thought it was Pick's disease, but that he would refer her to the London Hospital for a conclusive diagnosis. He told me Pick's was a brain disease that killed off some cells, but wouldn't give too many details. I found out for myself.

Maura carried on working and driving, I had explained to her boss that she had a brain disease and we were waiting for further tests. She said they knew Maura had a problem, but they had been working round it. Maura began get tired early in the evening and I persuaded her to start sleeping in the afternoon, she was always up at 5.30 am for a 7o'clock start and she needed more sleep. October and she was constantly tired, I knew I should talk to her boss again, but if I did it might bring matters to a head and she may lose the job that meant everything to her. November and an appointment at the London hospital, they also suspected Pick's. I was advised to talk to her boss, but that was too hard for me to do as I was going to be responsible for taking away something from her.

She caught Flu in November and had three days off work sick, her first in four years. She also got an ear infection, I took her to the Doctors on a Monday morning 23, November and when we went in I could see the GP willing out a sick note. It happened that my wife's boss had written to the surgery expressing concern and wanting details, which they were given. The GP thought my wife had already been laid off and was giving her a Doctors note for sick leave. When we got back from the surgery there was a letter waiting, it was from her boss; she wanted to meet with us to arrange the kind of work Maura could do. She could no longer be a care assistant but they knew how much her work meant to her and would find her domestic work. We agreed a roster and hours; Maura went once on Saturday 28 November, she had to make beds all day and she never went back.

That was also the last day she drove her car, she just ignored it from then on. I have been leaving her at home on her own, while I was at work since then, but I was not comfortable with it. I left her soup to warm in the microwave and rolls to eat. The first week I did this it was fine, I phoned everyday at l o'clock to check she was OK, I left her notes explaining that she should pick up the phone if she had a problem, she never picked up the phone. When I got in from work she would be pleased to see me. I cooked dinner and we all ate together. The second week she ate six tins of soup in two days and picked up the phone, I rushed home but there was no problem, she was just sitting looking out of the window; the TV wasn't on as it usually was. Going to work got harder, getting home was more urgent I was off most of Christmas and someone was here most of the time with her. I have asked for help, it is slow in coming. I went back to work after New Year, but couldn't relax. I'm off sick myself now for a month at least. There is no facility for early onset dementia in this area and the only day care centre is short staffed and can't take her.

I'm hoping that during this month Social Services can work a care program and I can go back to work. I also have to sort out the mess she got in with money. She has three credit cards and a bank loan. Recently, after I discovered her debits she allowed me to begin managing her bills and payments. When she last paid her bills by cheque she made all to the cheques out to herself. I have Enduring Power of Attorney now, I got a self completion pack from Eagle Legal Forms Ltd. 3 Kestrel Way, Squires Ride Estate. Buckingham Bucks MKI 8 7HJ and it cost £6.99.

Maura has become more childlike over the last few weeks and plays with talking toys - I think this is to attract attention. She has begun to neglect her appearance and sometimes has to be told to wash her hair. Her interest in football remains, but now we have to watch every bit of football that is on TV; I don't think she can follow a plot in a film anymore. Her sounds now are varying types of OHHH, to denote whether she is angry or wants say something. She writes very cryptic notes for me, of one or two words and I have to guess what she is trying to say. She hides the notepads if we get visitors and communicates by smiling or nodding. I find it really strange that that she is calmly accepting all that is happening to her, she can't walk very well, or talk but she seems happy in herself. She seems to enjoy the attention she gets from doctors and nurses. I think she believes I am someone who is here to look after her.

I took her to a day centre for old people this week as part of a care package that Social Services are trying to devise and she sat quite happily as though it was meant to be. Cleaning, washing and ironing are things she became compulsive with. We are not allowed to make anything untidy so always tidy up as we go to avoid her banging things and shouting OHHHHHH. We don't go out anymore, a trip to the supermarket is the highlight of the week. In two years Maura has gone from a happy outgoing woman, who had a beautiful voice, with a lovely Irish accent, to the way she is today. I read Frank and Mary's story and couldn't decide how many years Frank suffered, but it was a long time. I now suspect that Maura has had Picks disease since we married in 1981. Things that I thought were just quirks in her nature, such as not talking to me for three or four days, smashing things after a night out and things she would say to people, were all part of this disease. I don't know what the future holds or how long she has left; the not knowing is what makes it harder.

Barry Rowley
 

International Conference on Pick’s Disease & Frontotemporal Dementias Thursday-Friday, May 6-7, 1999  DoubleTree Hotel Philadelphia, PA USA  This is the first international assembly of scientific/medical and related professionals and caregivers interested in Pick’s Disease and FD. The two-day Conference is jointly sponsored by the Alzheimer's Association Southeastern Pennsylvania Chapter and Friends Hospital.            The topics to be addressed:  Clinical Assessment  Molecular Biology  Histopathological Abnormalities  Therapy and Management  Caregiver Issues.  For more information you can e-mail lradin@bellatlantic.net Or visit the website at http://www.isl.net/~hoffcomp/pickscnf.html

AGM 1999

Business.
The AGM and seminar for the PDSG were this year held in Nottingham. The business part of the proceedings began with the election of officers. Peter Thompson was unanimously elected as Treasurer. He has already made sure that our accounts are in good order. The committee expressed thanks to Margaret Butler and Claire Bream (good luck with number 2!) for setting up our accounts. Lynn Lingham was also elected as a carer representative on the committee. Penelope was re-elected as secretary. The chairman mentioned how glad he was to see the success of the roadshow and the booklets. Also the poster which was used to good effect at the symposium at the Queens Medical Centre in Nottingham in October where rare dementias were well represented.

Chairman's Speech
The Chairman thanked John Jennings for the setting up and supervision of the web pages and the design of the poster. He also thanked Peter Davis who does all our printing and is incredibly generous to our group. Roberto Salina was thanked for organising the database (from Italy). Peter Thompson also received thanks for kindly fundraising for us. We expressed our ongoing thanks to Professor Martin Rossor for heading our medical committee. The Chairman also thanked *Penelope and Carol*! Thanks must go to all those people who have supported us, often in lieu of flowers in memory of their loved ones. The Chairman's speech reminded us that we are a carer's group concentrating on carer's needs. This was reflected in our seminar. David stressed how much we have achieved in the past year to promote awareness.

Seminar.
Professor Jim Lowe gave a wonderful presentation about recent advances in our understanding of the role of Tau. Tau is a protein that is implicated in nearly all of the dementias. (This means that much more research will be concentrated on our dementias). This was followed by Carol talking about the practical needs of carers and Penelope who gave an overview of our dementias. Wendy Wells then gave a very positive account of caring for her husband who has Pick's Disease. She emphasised the importance of planning within routines and stressed how vital to bolster the feeling of self-worth of the person with dementia. Wendy also wished that more people would ask how they could help rather than telling her what she should do. Lunch was delicious. Ann Johnson gave a lovely account of the work for younger people with dementia at The Rowans in Shrewsbury. The whole seminar provided a great opportunity for carers and professionals to exchange ideas and information.

Penelope Roques and Carol Jennings

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