Monday August 18 2014
Parkinson's disease is caused by a loss of nerve cells
“Depression more common in early Parkinson’s,” BBC News reports, as a new study investigates the impact this degenerative condition can have on mental health.
Parkinson’s disease is a neurological condition caused by a lack of the chemical dopamine in the brain. Alongside the characteristic movement symptoms such as involuntary shaking, mental health symptoms including depression, anxiety and dementia are relatively common in people with Parkinson’s.
However, it is unclear whether these symptoms are directly caused by the disease process of Parkinson’s or whether there are other factors (for example, psychosocial) that may be involved in both.
This study compared people with newly diagnosed Parkinson’s disease and healthy controls over two years to see if symptoms developed and changed.
The researchers found that depression, fatigue, apathy and anxiety were more common at the time of diagnosis in people with Parkinson’s disease than healthy controls. Apathy and psychosis also increased over the two years in people with Parkinson’s.
This study demonstrates how a variety of mental health problems can be common in early Parkinson’s disease, something patients need to be aware of.
But we do not know whether these symptoms had newly developed as a direct result of the disease process, or whether these symptoms were present long before, or whether they even arose due to the “shock” of diagnosis.
Read more advice about living with a long-term condition.
Where did the story come from?
The study was carried out by researchers from University Hospital Donostia, San Sebastián, Spain; Perelman School of Medicine at the University of Pennsylvania; and the Department of Veterans Affairs at Philadelphia VA Medical Center, US.
Funding was provided by the Michael J. Fox Foundation for Parkinson’s Research and the following funding partners: Avid Radiopharmaceuticals, Abbott, Biogen Idec, Covance, Bristol-Myers Squibb, Meso Scale Discovery, Piramal, Eli Lilly and Co, F. Hoffman-La Roche Ltd, GE Healthcare, Genentech, GlaxoSmithKline, Merck and Co, Pfizer Inc, and UCB Pharma SA.
The study was published in the peer reviewed medical journal, Neurology.
BBC News’s reporting of the study was accurate and included some useful quotes from independent experts.
What kind of research was this?
This was a prospective cohort study that aimed to look at the course of mental health and cognition symptoms over two years in people with newly diagnosed Parkinson’s disease.
Parkinson’s is a neurological condition caused by a lack of the chemical dopamine in the brain that affects the nerve cells. This causes characteristic symptoms including tremor, rigidity and slow movements. Mental health symptoms including dementia, depression, anxiety, and sometimes psychosis (such as hallucinations and delusions), have also long been associated with Parkinson’s.
However, as the researchers say, it is unclear to what extent these “neuropsychiatric symptoms” are caused by the general degeneration of the nerve cells that occurs in Parkinson’s, or whether they could be caused by other psychosocial factors. Another possibility is that they could arise as side effects of the drugs often used to treat Parkinson’s.
So looking at a newly diagnosed, untreated population of people with Parkinson’s and following them through the first two years of their condition should help to see how these mental health symptoms develop and progress.
What did the research involve?
This research was called the Parkinson’s Progression Markers Initiative (PPMI) study, which was an international study conducted in 16 US and five European sites. The study enrolled 423 people with newly diagnosed Parkinson’s disease, who met diagnostic criteria for the condition, had not yet received any treatment and were currently free from dementia. As a comparison group they enrolled 196 healthy controls without the condition.
A subset of people with Parkinson’s and healthy controls were assessed at baseline, 12-month and 24-month follow-up. People with Parkinson’s only had also been assessed at six months.
The assessments at baseline and each follow-up point included:
- depression on the Geriatric Depression Scale
- cognitive ability on the Montreal Cognitive Assessment (MoCA)
- impulsive behaviour (compulsive or repetitive behaviours due to poor control, such as gambling, sexual, eating, excessive wandering) on the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease
- excessive daytime sleepiness on the Epworth Sleepiness Scale and other sleep disorders on the REM sleep behaviour disorder screening questionnaire
- movement disorders and other aspects of disease severity on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale
- anxiety on the State-Trait Anxiety Inventory
- sense of smell on the University of Pennsylvania Smell Identification Test
People with Parkinson’s could start treatment with dopamine replacement therapy (often levodopa) at any time after diagnosis. Dopamine replacement therapy is designed to help improve symptoms, though side effects can be wide ranging.
They were considered to have received treatment if they had been prescribed it for at least one year, and were still prescribed the treatment at the end of the study (the two-year follow-up). Treatment had been started by 9.6% of patients with Parkinson’s disease at six months, by 58.8% at 12 months and 81.1% at 24 months.
Comparisons were made between the Parkinson’s and control groups.
What were the basic results?
Overall, people with Parkinson’s had significantly more symptoms of depression, anxiety, fatigue and apathy at all time points compared to controls, and symptoms of apathy and psychosis increased over time in the people with Parkinson’s.
At enrolment 13.9% of people with Parkinson’s disease and 6.6% of healthy controls screened positive for depression on the GDS.
There was a non-significant increase to 18.7% of people with Parkinson’s disease having depression at 24 months, compared to a decrease to 2.4% in the health control group. The proportion of people with Parkinson’s disease taking an antidepressant increased from 16% at baseline to 25% at 24 months.
The average MoCA score of people with Parkinson’s disease decreased significantly from 27.1 at baseline to 26.2 at month 24. The cutoff for mild cognitive impairment is below 26. Using this cutoff, 21.5% of people with Parkinson’s disease were cognitively impaired at baseline, 34.2% at 12 months, and 35.5% at 24 months. Mean scores in the health control group also decreased overtime from 28.5 at baseline to 27.7 at 24 months.
Other neuropsychiatric symptoms
The proportion of people with Parkinson’s disease with positive scores on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale for fatigue and apathy at baseline was 50% and 16.7%, respectively, increasing to 61.5% and 30.2% at 24 months. These proportions were significantly higher than the health control group at all timepoints. Similarly, anxiety symptoms were significantly higher in the Parkinson’s disease than health control group at all timepoints, though anxiety scores did not increase over time in the Parkinson’s disease group. The prevalence of psychosis symptoms increased in the Parkinson’s disease group from only 3.0% of people at baseline, to 5.3% at 12 months and 10% at 24 months.
The proportion of people with Parkinson’s disease with impulsive behaviour symptoms was 21% at baseline and did not significantly increase during follow-up; nor was there a significant difference between Parkinson’s disease and health controls at any time point. There was a trend for daytime sleepiness symptoms to increase in people with Parkinson’s disease, but again no significant difference was seen compared with health controls.
Relation to treatment
At 24 months, 81% of people with Parkinson’s disease had started dopamine replacement therapy, and 43.7% had been taking it for at least one year. This group reported significantly more new problems with impulse control and excessive daytime sleepiness compared to baseline.
How did the researchers interpret the results?
The researchers conclude that multiple neuropsychiatric problems are more common in newly diagnosed, untreated people with Parkinson’s compared with the general healthy population. These problems tend to remain relatively stable in early disease, while cognition slightly deteriorates. Starting dopamine replacement treatment is associated with increasing frequency of several other neuropsychiatric problems.
This cohort study benefits from its prospective design, following a group of people newly diagnosed with Parkinson’s disease across the course of two years compared to a group of healthy controls. It also benefits from being an international, multicentre study including a fairly large sample size, and from conducting regular symptom assessments using a series of validated tools.
However, there was quite a high loss to follow-up. From 423 people with Parkinson’s assessed at study start, 62% were available for 12 month follow-up, and only 23% at 24 months. This is an important limitation that may affect the reliability of the results.
The study demonstrates that people with Parkinson’s already at the time of diagnosis seemed to have higher symptoms of depression, anxiety, fatigue and apathy than the healthy controls. The proportion of people with Parkinson’s who had fatigue and apathy increased over the two years. Also the proportion with symptoms of psychosis, though low, did increase throughout the study.
Cognitive ability deteriorated significantly over the two years of the study in people with Parkinson’s disease.
The use of dopamine replacement treatment was associated with the development of new symptoms of impulse control and excessive daytime sleepiness. However, these results were based on a small sample.
Therefore, the study provides us with an indication that certain mental health symptoms of depression, anxiety, fatigue and apathy may already be present at the time that Parkinson’s is first diagnosed.
This suggests that these symptoms are not likely to be caused by Parkinson’s treatment, as the people hadn’t started treatment yet, but it can’t really tell us much more about how they developed.
It seems possible that they may be caused by the general nerve degeneration process that happens in the development of Parkinson’s. However, we don’t know whether these symptoms may have been present long before the person developed Parkinson’s (such as whether the person had a lifetime history of depression and anxiety problems). Therefore, we don’t know overall whether they are caused by the Parkinson’s disease process.
It could be the case that there are other genetic, health psychosocial or lifestyle factors involved in the relationship that may put the person at risk of both these mental health conditions and Parkinson’s.
This study is a valuable contribution to the research into Parkinson’s disease and its associated mental health symptoms. But unfortunately it provides no solid answer to the direct cause of development all of these symptoms.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.