People With Down Syndrome Are Pioneers In Alzheimer's Research

by Jon Hamilton from NPR:
When researchers at the University of California, San Diego wanted to study an experimental Alzheimer's drug last year, they sought help from an unlikely group: people with Down syndrome.
"I had a CAT scan on my head, and I was in a special machine. It's called an MRI," says Justin McCowan, 39, whose parents drove him 125 miles from Santa Monica so he could participate in the study. McCowan also took brain function tests and spent hours with a needle in his arm so researchers could monitor levels of certain chemicals in his blood.
Alzheimer's researchers are increasingly interested in people like McCowan because "people with Down syndrome represent the world's largest population of individuals predisposed to getting Alzheimer's disease," says Michael Rafii, director of the Memory Disorders Clinic at UCSD.
Down syndrome is a genetic disorder that's best known for causing intellectual disability. But it also causes Alzheimer's. "By the age of 40, 100 percent of all individuals with Down syndrome have the pathology of Alzheimer's in their brain," Rafii says.
Down syndrome is caused by the presence of an extra copy of chromosome 21. And one of the genes on chromosome 21 happens to control the production of amyloid, the substance that forms the sticky plaques associated with Alzheimer's.
Because their bodies produce extra amyloid, most people with Down syndrome develop problems with thinking and memory by the time they reach 60. Rafii has chronicled the decline of one of his patients, a woman named Irma, by collecting her signatures from medical forms over the years.
The first one is from 1999, when Irma was in her mid-50s. "You can see her signature is on the line, it's clear, she wrote it in script," Rafii says. By 2005, though, she has switched to large block letters. By 2009, Irma is misspelling her name. By 2011, "there are only a few characters written that resemble letters," Rafii says. "And in the very last year it's completely blank."
People like Irma used to be rare because the medical problems associated with Down syndrome meant they rarely lived long enough to get dementia. Today, though, better medical treatments mean people with the disorder often live into their 60s.
And that has created a huge opportunity for Alzheimer's research, says William Mobley, chairman of the neuroscience department at UCSD. "This is the one group in the world that you could argue would benefit most by the institution of early therapy," he says.
Early therapy means starting people on drug treatment years before the symptoms of Alzheimer's appear. The approach has been hard to test because, in the general population, there's no good way to know who is going to develop Alzheimer's. But for people with Down syndrome, it's a near certainty.
Finding a drug that prevents Alzheimer's in people with Down syndrome could help millions of people who don't have the disorder, Mobley says. "This approach to treating Alzheimer's disease might apply to all of us," he says. "Imagine someday a drug that we all start taking when we're 25 so we never get Alzheimer's disease."
That's a long-term goal. But already, people with Down syndrome are making a difference in Alzheimer's research. Early work with Down patients helped confirm the importance of amyloid. More recently, people with the disorder helped test an eye exam that may offer a simple way to screen for Alzheimer's.
And then there's the study that Justin McCowan signed up for. It involves a drug from Transition Therapeutics called ELND005 that, in mice, can prevent the brain changes associated with Alzheimer's. Scientists hope the drug can do the same thing in people, including those with Down syndrome.
McCowan says he volunteered for the study because he wants to help other people, especially a friend of his named Maria, who also has Down syndrome. "I feel very sad about Maria because she doesn't remember anything," McCowan says.
His parents, Don and Annamarie McCowan, say their son's memory is still sharp. They hope that what scientists are learning from people like Justin will keep it that way.

Down syndrome stem cells used to model Alzheimer’s

The scientists used skin cells donated from healthy volunteers and those with Down’s syndrome and turned them into stem cells. These stem cells were then used to generate networks of functioning nerve cells in the lab, which resemble the complex wiring of cells in the human cerebral cortex. The cortex, which makes up over three quarters of the brain, houses many of the nerve cells involved in memory and thinking and suffers particular damage during Alzheimer’s.

People with Down’s syndrome have an extra copy of chromosome 21, a segment of DNA that carries a gene responsible for producing the Alzheimer’s protein amyloid. Due to this extra version of the gene, people with Down’s syndrome have a much higher incidence of Alzheimer’s than the rest of the population. By generating nerve cells from skin cells of people with Down’s syndrome, the scientists could observe the disease process over a period of weeks and compare this to those cells derived from healthy volunteers.

Dr Rick Livesey, who led the study at the Wellcome Trust and Cancer Research UK Gurdon Institute at the University of Cambridge, said: “One of the biggest challenges facing dementia researchers at the moment is a lack of good ways to track the disease over time. By using stem cells donated from people with Down’s syndrome – who are much more likely to develop Alzheimer’s – we have been able to track how the disease develops over a shorter time period than has been possible in the past.”

Within 28 days, the nerve cells made from people with Down’s syndrome showed more than double the amount of the Alzheimer’s protein amyloid than those from healthy volunteers and this built up into amyloid plaques within two months. The scientists also observed that a protein called tau became abnormally altered and distributed in the cells- one of the common later-stage characteristics of the disease.

Dr Livesey added: “What is promising about this stem cell technique is that we can create functioning human cortex cells in a dish, allowing us to more closely model what is happening in our brains. Not only this, but our new model shows many of the characteristic features of human Alzheimer’s disease and will allow us to test new treatments more easily.”

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, welcomed the findings. He said: “We are pleased to have contributed funding towards this study and we hope it can be used to unravel some of the remaining questions about how Alzheimer’s progresses.

Modelling a complex disease like Alzheimer’s is a big challenge, but innovative approaches like this can improve our understanding. As the stem cells in this study were donated by people with Down’s syndrome, they differ genetically to the rest of the population, but could still offer valuable insight into the disease processes in Alzheimer’s.

“Increasing our understanding of dementia is essential not only for people with Down’s syndrome, but for the 820,000 people across the UK living with the condition. It is essential that we improve the models that we have for understanding dementia, but this can only be done through research. As dementia research is so desperately underfunded, we must invest now if we are to find the answers that are so urgently needed.”

from the University of Cambridge

Down syndrome and Alzheimer's

from newstimes.com:

Dear Readers,

I would like to stray from our regular pattern of answering one of your emails or letters. The reason for this is a particular topic which many of you brought up during a recent lecture given by geriatrician Marina Blagodatny and psychiatrist Neil P. Dolan at the Trumbull Marriott.

The topic in question was dementia, specifically Alzheimer's dementia in people with Down syndrome. I hope that you do not mind my taking the opportunity to write about it some more.

Let's start with the definition of Down syndrome. It is a genetic disorder affecting one in 733 live births and accounts for about 15 percent of intellectual disabilitiy cases.

Symptoms of the learning problems associated with the syndrome range from mild to moderate, as does the patient's functional capacity. The cause of this disorder is, most of the time, an extra chromosome -- or genetic "building block" -- in our body. Chromosome 21 is the one affected. Normally a person has two copies of each of the chromosomes.

In at least 90 percent of Down syndrome cases, a person has three copies of Chromosome 21. This is not an illness one inherits from a parent, at least not in a majority of cases. The most commonly known risk factor is late maternal age. By age 45, a woman's risk of having a baby with this disorder is one in 35.

Life expectancy of patients with Down syndrome has increased dramatically in the last century. From roughly 10 years in the 1920s, it is now quite normal for those with Down syndrome to enjoy life way beyond age 50.

Unfortunately, there are many problems these patients and their families have to struggle with throughout their lives. People born with the syndrome age faster, and are prone to developing dementia.

It is known that 25 percent of Down syndrome patients have dementia by age 35. They are three to five more times more likely to get dementia as compared to patients the same age not born with the genetic disorder.

What is most perplexing is the fact that, although virtually all adult patients with Down syndrome have specific changes in the brain characteristic of dementia, not all of them have the symptoms.

For those of you who are more scientifically inclined, the changes are called neurofibrillary tangles and amyloid plaques, as well as loss of nerve cells in certain parts of the brain.

It must be clarified that people with other forms of intellectual disability not related to Down syndrome have the same risk and rate for dementia diagnosis as the non-affected population.

Scientists still do not fully understand why this is the case, other than that the Chromosome 21 abnormalities must play a significant role. Alzheimer's disease is the most common form of dementia. It is a progressive memory disorder that affects our ability to reason, remember, use language and think.

The disease can attack quickly and lead to demise in only a few years, or linger over 10 to 15 years, affecting not only the patient but the whole family. Approximately 4 million Americans are affected today by Alzheimer's. Presentation of the disease in patients with Down syndrome is quite different from that in other dementia patients.

Loss of language skills and the ability for self-care are quite common early. Seizures happen often in individuals who did not have them before. Incontinence, personality changes and sleep disruptions are also seen.

Since the mental abilities of patients with Down syndrome vary greatly to begin with, diagnosis of dementia is challenging. Unfortunately, the majority of patients are diagnosed late in the process of the illness. Standardized tests used in non-Down syndrome individuals do not apply to this group.

It is crucial for a specialist involved to have some idea of the person's cognitive baseline. Many advocate for the universal screening of Down syndrome individuals around age 30. There is a questionnaire called "The Dementia Questionnaire for Mentally Retarded Persons," which can help, as well as a few other available tools. As a rule, a specialized dementia center is the best place to follow a patient with Down syndrome and Alzheimer's. The input from the caregivers and the primary care physician are considered absolutely necessary for the proper diagnosis and the meaningful follow-up.

One of the important goals of early diagnosis is to rule out other reasons for cognitive decline and behavioral problems that can be potentially curable. Thyroid problems, excessive medication use, severe depression, and unrecognized hearing and vision problems may all present as similar or identical to Alzheimer's. Even simple infection can trick us.

The treatment of Alzheimer's dementia in Down syndrome patients is uncharted waters. Only one out of four drugs available has been tested in these patients, and no drug is specifically approved by the Food and Drug Administration. Trying them, however, may prove very beneficial, as they may help with behaviors and stabilize functional abilities.

Other medications, like antidepressants, mood stabilizers and anti-anxiety medications, may also play a role when used judiciously and closely supervised and monitored.

There is yet another reality of this particular scenario. Many primary caregivers of Down syndrome patients in their 40s and 50s can be their aging parents and/or siblings. Not only do they have to face their own fears about forgetfulness and their own memory lapses, they are often unable to meaningfully plan ahead.

Legal issues are important, as well as financial ones. There has to be a plan of care in case of a caregiver's illness or, as horrible as it is to think about, death.

I strongly recommend that all involved use their local Alzheimer's Association, as well as local Down syndrome support groups and the National Down Syndrome Society. The help of local religious organizations also can be priceless. Government support is available, albeit limited. All of us professionals involved in diagnosis and treatment of dementia are more than willing to help.

Dr. Beata Skudlarska is a Bridgeport geriatrician. Send questions to Bridgeport Hospital Center for Geriatrics, 95 Armory Road, Stratford CT 06614 or geriatricmd@aol.com.

More People with Down syndrome developing dementia

from channel4.com:

People with Down's syndrome are living longer than ever before. Since the 1980s their life expectancy has doubled and many now live into their 60s.

But for the estimated 60,000 people with Down's syndrome in the UK this development is coupled with the startling knowledge that people with Down's are significantly more at risk of developing dementia than in the rest of us. Not only that but they also develop it at a much younger age - 30 to 40 years earlier than the general population.

Charlene is just 29 and was diagnosed with dementia six years ago. Her mum has witnessed her change from a fun-loving, karaoke-singing young person to "an old lady". Previously unaware of the high prevalence of dementia in people with Down's, it was a shock for the family to learn that Charlene was developing the disease in her early 20s.

Charlene is unusually young to start developing dementia, but studies do show that the risk increases dramatically with age. By 50, half of people with Down's are at risk of developing dementia, and this, in turn, is presenting a huge burden to families and services.

With an aging Down's population, Diana Kerr, a leading expert in the dual diagnosis at University of Edinburgh, worries that local authorities are not ready to meet the increasing demands of this population - partly because of a false perception that people with Down's don't live long enough.

Often changes in personality are the first sign of dementia, and a diagnosis is crucial for accessing the right services. It also means the family or carers can begin to change their responses and environment to make life more manageable for the person with Down's.

In Bradford, Nicole has Down's syndrome and lives with her sister Jackie. Nicole's changing behaviour is causing the family and her daycare service great strain. At 52 years of age there is a high probability this change in her character is due to the onset of dementia.

Recently has she been allocated a social worker to help begin the diagnostic process with Bradford District Care Trust. Dr Baylis is part of a multi-disciplinary team which will try to diagnose Nicole. She has other health conditions that could mimic dementia-like symptoms, so a clear diagnosis takes some time while other problems are ruled out.

But Diane Kerr insists that many options for carers are not costly and that simply training families and staff "who are supporting people with dementia to get into their world, instead of expecting them to get into our world," could greatly improve the situation for all concerned.

However, the default care option for many people with Down's no longer able to remain at home is to be placed in a care home for the elderly. Diana Kerr's findings warn that this is generally not the best solution. It may be cheaper than specialist dementia care for those with a learning disability, but there is often a lack of understanding among staff about the unique care needs involved. 

Down's syndrome facts
- Around one in every 1000 babies born in the UK will have Down's syndrome.
- There are 60,000 people in the UK with the condition. 
- Although the chance of a baby having Down's syndrome is higher for older mothers, more babies with Down's syndrome are born to younger women. 
- Down's syndrome is caused by the presence of an extra chromosome in a baby's cells. It occurs by chance at conception and is irreversible. 
- Down's syndrome is not a disease. People with Down's syndrome are not ill and do not "suffer" from the condition.
- People with the syndrome will have a degree of learning difficulty. However, most people with Down's syndrome will walk and talk and many will read and write, go to ordinary schools and lead fulfilling, semi-independent lives.
- Today the average life expectancy for a person with Down's syndrome is between 50 and 60. A considerable number of people with Down's syndrome live into their 60's.

Information by The Down's Syndrome Association

For Elaine in Cardiff this is something that she worries about daily. She cared for her daughter Mandy until dementia rapidly took hold in her 40s, when the burden on Elaine became too great. She ended up in hospital and Mandy was placed in a local care home.

Elaine visits the care home daily, and pushes to make sure that Mandy receives as much support as she can get. Where she thinks there is a shortfall in the available support, Elaine tries to fill it herself - such as trips to the physiotherapist so Mandy can stand for just a short time every week. Nationally, there are few facilities that cater specifically for those with Down's syndrome and dementia. As more and more people develop dementia, experts warn that, due to a lack of resources, more will end up in homes for the elderly, like Mandy.

While families and services provide varied support to people with Down's syndrome, scientists at Cambridge University are seeking treatments that could prevent future generations getting dementia at all. Professor Tony Holland has recently received funding from the Medical Research Council for a four-year study into a protein called amyloid.

'If we do not do something about the needs of people with Down's as they get older and have developed dementia, they will go back into the institutions that we have spent the last 20, 30 years trying to get them out of.'

People with Down's have unusually high levels of amyloid in the brain, and Professor Holland wants to find out if this is the driving force behind dementia in those with Down's syndrome.

If the study concludes that this protein is the key factor, the next step will be to find treatments that reduce the amount of amyloid being deposited in the brain - and thus attempt to prevent the onset of dementia in the Down's population.

Furthermore, it might offer key insights into the role of amyloid in Alzheimer's disease in the general population.

However until a medical breakthrough can defeat dementia, Diana Kerr fears that recent improvements in quality of life for people with Down's could quickly regress.

"If we do not do something about the needs of people with Down's as they get older and have developed dementia, they will go back into the institutions that we have spent the last 20, 30 years trying to get them out of - long-stay units where they are left in a bed, where they can restrain people with chemicals so they don't have to tie them down.

"And we've gone back 30 years. You know that thing about the mark of a civilised society is the way we support vulnerable people? Well, that would be a pretty big indictment."