With Alzheimers in the genes,when do you test?

At 5,Gary knew to avoid the prairie dog town,fearful his grandfather might stumble over one of the holes that the rodents burrowed into the grassy plain.

Occasionally,his grandfather would stop; his eyes took on an eerie stare that spoke of an empty place one that once was filled with memories,laughter and toil.

In 1945,nobody knew that Garys grandfather had a rare form of Alzheimers disease that would strike 10 of Garys 14 aunts and uncles,his father and his only brother and sister in the prime of their lives.

Garys family has dominantly inherited Alzheimers disease. It is rare,and it afflicts the young. In his family,symptoms can appear in the early 40s.

This inherited form of Alzheimers is caused by mutations in one of three genes: amyloid precursor protein,presenilin 1 or presenilin 2.

It is the only form of Alzheimers for which there is a diagnostic test that can predict with certainty whether Alzheimers will ensue.

That may change. Researchers,patient advocates and policy makers are pushing for earlier testing of Alzheimers,in part because it will help the search for a cure. That means more people could find out if they will succumb to the disease.

But without a treatment or a cure,would people want to know?

Surprisingly,yes,said Dr Robert Blendon,professor of health policy and political analysis at the Harvard School of Public Health.

Blendon conducted a survey of 2,678 adults from five countries that was released on Wednesday at the Alzheimers Association International Conference in Paris. About two-thirds of respondents said they were likely to get a test to predict whether they would get Alzheimers before any symptoms appeared.

Some 35.6 million people worldwide have Alzheimers,the most common form of dementia. Drugs only help symptoms; none can arrest Alzheimers,which costs $604 billion a year globally to treat.

All of the drugs that have been tried in people with advanced dementia have failed to slow the disease,and many experts think the reason is that they were tried on people who were too far gone.

Some people who know Alzheimers may lie in wait make different life choices. They take more extravagant vacations,they put their finances in order earlier than many other people. They even may use a surrogate parent instead of taking a chance of passing on the disease to a new generation.

Early prevention,early treatment

There are no tests that can detect Alzheimers before symptoms appear,but researchers are getting closer.

Eli Lilly and Co is seeking US Food and Drug Administration approval to sell an Alzheimers imaging agent for use with positron emission tomography,or PET,scans to help doctors rule out Alzheimers.

Scientists are also looking for signals of Alzheimers in cerebrospinal fluid. These tests look for two Alzheimers-related proteins: beta amyloid,which forms sticky plaques in the brain,and tau,a marker of cell damage. Low levels of beta amyloid in spinal fluid suggest it may be accumulating in the brain,and high tau levels suggest nerve cell death.

Some doctors already test for this to confirm that Alzheimers has caused a persons dementia.

Encouraged by these steps,National Institute on Ageing,part of the National Institutes of Health,and the Alzheimers Association in April revised the diagnostic criteria for Alzheimers for the first time in 27 years to recognise mild cognitive impairment as a precursor to the disease.

They also added a new research category called preclinical Alzheimers,the earliest stage of the disease when clumps of amyloid start to form in the brains of people who are otherwise healthy.

This stage,which occurs some 10 years before dementia sets in,is seen as the best place to intervene. It is why new imaging agents for PET scans,spinal fluid tests and so-called biomarkers that predict Alzheimers are becoming so important to researchers and drug companies.

The guidelines portend a lot more than just how to diagnose Alzheimers today, said Dr Daniel Skovronsky,founder and chief executive of Avid Radiopharmaceuticals.

I think many people now have a sense of hope that some day we can make Alzheimers a preventable disease,and that is through early prevention and early treatment, he said.

Dian trial

A clinical trial known as the Dominantly Inherited Alzheimers Network,or DIAN,is studying families with inherited forms of Alzheimer’s to learn more about how the disease progresses.

Funded by a grant from the National Institute on Ageing in 2008,DIAN has the largest and most extensive worldwide research network investigating dominantly inherited Alzheimer’s,with sites in the US,Britain and Australia.

Initial results from the study presented at the Alzheimer’s Association meeting suggest inherited forms of the disease can be detected as many as 20 years before problems with memory and thinking develop.

Anxiety

Despite all the hope,some doctors and social workers who treat Alzheimers and care for their families say the push for early testing is premature.

The tests are so inaccurate at this point that I dont know what the value is other than to create a lot of anxiety, said Debra Greenberg,geriatrics social worker at Montefiore Medical Center in New York.

Other Alzheimers experts see value in early diagnosis.

We think right now,today,there is a clear benefit of an early diagnosis, says Bill Thies,chief scientific officer of the Alzheimers Association.

One reason is that studies suggest people who understand the course of Alzheimers disease and what to expect from it cope better with the disease. This is true of patients and caregivers, Thies said.

Gary says it is common among the younger members of his family not to get tested. They say,maybe when Im 50, but I dont want to know now. Gary had no idea of the weight of his burden of living with the threat of Alzheimers until the day he found out he did not inherit the gene.

It was joyous relief. I just wanted to sing. And then,there was just this horrible weight of grief and sadness because of not only my brother and sister,but all of the other members of my family I have seen who have lived through this.