16:20 21-11-2014
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Tests that could spot Parkinson's decades before symptoms launched

Bishkek (AKIpress) - laboratory study Parkinson's disease affects all cultures and races. Globally, it is estimated 6.3 million people have the disease.

Most sufferers are diagnosed later in life, on average at 65. But scientists now believe the disease begins to develop up to 20 years before the appearance of the first symptoms, such as uncontrollable tremor, slow movements or muscle stiffness. This means many people may have hidden Parkinson's in their 40s or earlier, Daily Mail reports.

“There's a lot of debate about this but it's thought patients may start to lose nerve cells in the brain anywhere between five and 20 years before symptoms appear,” says Claire Bale, research communications manager with the charity Parkinson's UK.

Now the race is on to develop new ways to identify patients during the “pre-onset” years, and give them a better quality of life.

Parkinson's is caused by a loss of nerve cells in an area of the brain that controls movement and feelings of reward and addiction. These cells produce dopamine, a chemical that shuttles messages between the brain and nervous system, helping to control body movement.

If these cells become damaged or die, levels of dopamine are reduced. Symptoms of the disease appear only when 80 percent of the nerve cells have been lost.

Parkinson's is diagnosed by studying a patient's symptoms and movement, often followed by a DAT scan, which measures dopamine levels in the brain.

Professor Patricia Limousin, a specialist at the National Hospital for Neurology and Neurosurgery in London, warns that the classic symptoms neurologists instantly look for often go unnoticed by GPs.

“We look for tremor, especially when the arm is at rest, and slowness of movement, reduced swinging of the arm when walking, and stiffness of muscles. Most patients have had some or all of these symptoms for months or years before they see us. Some may have noticed a slight tremor but didn't seek help, others have been to a GP but are told it's down to stress.”

The disease has been known about since ancient times – it was referred to as “shaking palsy” as early as AD175.

But what triggers it is still unclear. The consensus seems to be that some people may carry a mixture of genes that predispose them to damage by toxins in the environment – such as from pesticides – and this sets Parkinson's in motion.

Men are 50 percent more likely to get it than women. One theory is that oestrogen may have a protective effect.

For most people, having Parkinson's will not significantly affect life expectancy. But in its advanced stages it can lead to chronic pain, sleep disruption, anxiety and depression, and problems affecting movement. Years of being ill can leave patients vulnerable to infections.

The earlier Parkinson's is treated, the better, as currently drugs can slow down – but not halt – the loss of brain cells.

So scientists are trying to find easy ways to test for the condition in the early stages. One of the most promising is a blood test for raised levels of the protein alpha-synuclein. This is released in clusters in the brain when the disease is setting in – but usually before symptoms appear.

In 2011, scientists at Lancaster University discovered a way to detect the protein in blood samples of Parkinson's patients. Now trials are looking at whether an alpha-synuclein blood test could be the early warning sign doctors hope for.

An Austrian team is even testing a vaccine that could prime the immune system to attack and destroy the clusters. First results are due in a few months.

“Although we know alpha-synuclein is involved in nerve-cell death in the brain, there are many types of the same protein, and we are still some way off having a readily available blood test,” says Claire Bale.

There are other, perhaps slightly surprising, clues that Parkinson's may be developing.

One is a loss of smell. As brain cells die off, one of the areas of the brain affected fairly early is the olfactory bulb, which processes and identifies odors. Up to 80 percent of patients recall losing some or all of their sense of smell months or years before the onset of other symptoms.

Another potential early warning sign is constipation. As dopamine-producing cells die off, muscles controlling contractions in the bowel also seize up, because dopamine is produced by nerve cells in the enteric nervous system – which controls digestion. Around 60 percent of sufferers experience constipation early on.

“We think these nerve cells outside of the brain are affected earlier, or start to show symptoms earlier than those in the brain,” says Claire Bale.

A third indicator is vivid dreams, or acting out nightmares. At least five years before patients suffer stiffness, many have REM sleep behavior disorder.

Rapid eye movement sleep is the stage where we have vivid dreams. To stop us acting them out, the brain temporarily paralyzes us. But the damage to brain cells in Parkinson's switches off this mechanism.

Individually, none of these indicators are strong enough to confirm that Parkinson's has set in. But it may be that a collection of such warning signs could justify further investigation.

It's hoped new drugs could stop the progression of the disease altogether. Current treatments, such as levodopa – a drug which has been around for nearly 50 years – address only the symptoms by replacing some of the missing dopamine.

A more extreme treatment is deep-brain stimulation, where electrodes are implanted into the brain to “deactivate” affected areas.

It can ease symptoms, and patients are often able to reduce their drug dosage. This is vital: dopamine-replacing drugs have been associated with severe behavioral side-effects, such as gambling or sex addiction.

One of the most promising new treatments could be a relatively cheap drug already widely and used for type 2 diabetes.

Exenatide helps lower blood sugar levels. But a study with 20 patients last year at University College London found it appeared to slow down, or in some cases halt, the progression of Parkinson's. Bigger trials are planned.

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