Research interest in pre-clinical markers for Parkinson’s disease is fuelled by the desire to identify one or more biomarkers that can be used to provide earlier diagnosis of Parkinson’s and new treatments to delay or even prevent the progression of the disease.

Depression can be an early symptom of Parkinson’s

“Years before being diagnosed with Parkinson’s, I began experiencing bouts of depression. I sought treatment and was hospitalized in 1995. I also had electroconvulsive therapy. I wasn’t diagnosed with Parkinson’s until December 1998. After I began taking Parkinson’s medication, I did notice some improvement in my mood. I haven’t experienced depression since.” ~Peggy Sturge, Newfoundland

Many people experience depression after being diagnosed with Parkinson’s. However, what’s less well-known is that, for some people, depression is one of the earliest symptoms of Parkinson’s, appearing even before the onset of motor symptoms.

“Depression can be part of the disease itself and not just a reaction to having a neurological disease,” says Dr. Susan Fox assistant professor of neurology at the University of Toronto and neurologist at the Movement Disorders Clinic at Toronto Western Hospital. “There’s a lot of evidence now that mood disorders are part of the biology of Parkinson’s disease.”

Dr. Fox explains that people with Parkinson’s lose norepinephrine and serotonin. These are neurotransmitters that are involved in mood, in general, as is dopamine.

She says, “Many patients, as they’re starting to lose their dopamine, may not have yet developed a tremor, slowness, or trouble walking, but they may feel anxious and depressed. Some have an inner sense of anxiety; they feel shaky inside. And when they start on medication, it’s often resolved. They report that they feel relaxed and calmer inside.”

Dr. Fox notes that, whatever the cause, depression is treatable, and people experiencing depression should seek help from their family doctor.

Are older antidepressants better for Parkinson’s depression?

A study, published in the March 10, 2009 online edition of Neurology, has shown that the tricyclic antidepressant, nortriptylene, may be more effective than the selective serotonin reuptake inhibitor (SSRI), paroxetine, for treating depression in people with Parkinson’s disease.

“The tricyclic antidepressants are an older style of medication that has gone out of favour largely due to side-effects, such as sleepiness; so SSRIs tend to be prescribed,” says Dr. Susan Fox, assistant professor of neurology at the University of Toronto and neurologist at the Movement Disorders Clinic, Toronto Western Hospital.

This study suggests, however, that the tricyclic class of medications may be more effective for depression in Parkinson’s. The tricyclics affect both norepinephrine and serotonin whereas the SSRIs target only the serotonin receptors in the brain.

With only 52 patients, this is the largest placebo-controlled study for Parkinson’s disease depression, to date.

Considering that depression affects up to 50% of people with Parkinson’s disease and negatively affects their quality of life, further research is needed, particularly larger clinical trials.

The study was led by Dr. Matthew Menza, a professor of psychiatry and neurology, at the Robert Wood Johnson Medical School in Piscataway, New Jersey.

REM sleep disorder a risk factor for Parkinson’s

A recent study by Dr. Ron Postuma of McGill University in Montreal has shown that people with REM sleep behaviour disorder risk developing Parkinson’s disease or dementia.

In REM sleep behaviour disorder, you violently act out your dreams – punching, kicking, crying out or throwing yourself out of bed. You may even injure yourself or your bed partner.

Dr. Postuma’s research, at the sleep disorders laboratory at Montreal’s Sacré-Coeur Hospital, studied 93 patients, who had been diagnosed with REM sleep behaviour disorder, and followed them for 5, 10 and 12 years for signs of neurodegenerative disease.

The average age of the participants was 65 years. Eighty per cent were men.

After 12 years, 26 of the 93 patients had developed a neurodegenerative disease:
• 14 developed Parkinson’s disease
• 1 had Multiple System Atrophy (a related Parkinson’s condition)
• 11 had dementia

Using life table analysis to define disease risk over 5, 10 and 12 years, the study estimated a
• 17% risk of developing neurodegenerative disease at 5 years
• 40% risk at 10 years
• 52% risk at 12 years

The study, published online in the journal, Neurology, in December 2008, is the largest study attempting to quantify the risk of developing neurodegenerative disease for people with REM sleep behaviour disorder.

Seeking smell test for Parkinson’s

“I noticed I was losing my sense of smell in the 1990s when I was still working as a food inspector. Smell is an important tool for detecting freshness of food; so I told my supervisor about my problem. I went to my doctor but he couldn’t find a reason for it. He referred me to a neurologist who recommended an MRI but also had no answers. At that time, I had no tremor, no sign of Parkinson’s at all. It wasn’t until fall of 2004, that I was diagnosed with Parkinson’s.”  ~Arnold Forsyth, Nova Scotia

Dr. Harry Robertson, a professor in the Brain Repair Centre and Department of Pharmacology, at Dalhousie University in Halifax, is seeking to find a diagnostic tool that can capitalize on the fact that a majority of people with Parkinson’s lose their sense of smell.

“The general consensus is that the changes in olfaction (ability to smell) occur about five years before the Parkinson’s diagnosis,” says Dr. Robertson. “If we could stop the process, that is, stop the loss of the neurons, we could stop people from ever developing the severe symptoms of PD. That’s the dream – to stop the Parkinson’s before it becomes disabling. I’m sure smell testing is going to be one component of that.”

In the first phase of his research, Dr. Robertson will try to identify smell deficits in about 20 people between the ages of 45 and 65 who have been recently diagnosed with Parkinson’s.

Using diffusion tension imaging (DTI), a special type of magnetic resource imaging (MRI), he will measure changes in two areas of the brain – the olfactory tract, which is the pathway for the sense of smell and the substantia nigra, where neurons degenerate in Parkinson’s.

In the second and larger phase of the study, Dr. Robertson will test olfactory function in up to 500 or more people who have not been diagnosed with Parkinson’s. Participants will be given a booklet of scratch and sniff pages and asked to sniff the pages and try to identify the smells. People with the lowest scores, indicating the most impaired sense of smell, will then undergo the brain imaging.

Research participants are needed from the Maritime Region

You may be eligible to participate in phase one of Dr. Robertson’s research, if:
• You have been recently diagnosed with Parkinson’s.
• You are between the ages of 45 and 65.
• You are otherwise in good physical health.

The study is being conducted at Capital Health and the IWK Health Centre in Halifax.

For more information, contact Dr. Harry Robertson, (902) 494-2563, har1@dal.ca.