Neuroprotection and Parkinson’s
Slowing down or stopping the process of neurodegeneration remains one of the most important goals of current Parkinson’s research.
Until relatively recently Parkinson’s therapies focussed mainly on improving symptoms of Parkinson’s. However, new insights into the causes and progression of the illness have led to the development of disease-modifying agents that may affect the natural progression of the condition. The hope is that specific medicines can be developed to change some of the processes leading to cell death and so protect the remaining neurons. These medicines fall largely into the following categories:
- anti-oxidant – scavenging any harmful free-radicals that may cause cell damage
- anti-inflammatory – preventing harmful inflammation
- anti-apoptotic - preventing the self-destruction of cells
- anti-excitotoxic - preventing the process by which nerve cells are damaged and killed by various substances
- pro-mitochondrial - supporting the mitochondria which provide cells with energy.
Neuroprotection is quite a specialist area of research so your doctor or neurologist may not have detailed knowledge but will be able to refer you to a specialist who can provide more information.
Apart from the everyday products available in most supermarkets which are believed to have neuroprotective properties (caffeine, nicotine, ginseng and turmeric) - it is generally agreed that keeping your brain as active and challenged as possible helps it to stay healthier for longer. Doing puzzles such as Sudoku and crosswords, or mental arithmetic rather than using a calculator, really can help your brain function better, as can stimulating conversation and reading.
Various clinical trials are under way on a number of compounds in laboratory studies. Although many of the findings look promising there has been some controversy over the interpretation of results. This is partly due to the considerable difficulty in both designing appropriate trials and establishing effective markers and methods to evaluate the neuroprotective benefits of compounds.
Potential neuroprotective agents
There is much interest in the role of free-radical damage in Parkinson’s and other conditions. Free-radicals in moderation are normal but if there are more than the body can cope with, oxidative stress generally occurs which results in disease.
Anti-oxidants, both as supplements and in naturally occurring forms, have the ability to scavenge and neutralise free-radicals. Most scientists agree that the brains of people with Parkinson’s have too many free-radicals and not enough anti-oxidants to balance them out. Whilst anti-oxidants are no cure for the condition, many believe that they can help to slow the progression of Parkinson’s. However concrete scientific data to back up claims is limited and you should always discuss with your doctor before taking any supplements.
It is thought that certain Parkinson’s medications may have anti-oxidant properties and more research is underway to establish if this is the case.
Perhaps the simplest and most important theory relating to neuroprotection is that dopaminergic treatment, which supports the degenerating cells, can provide significant long term neuroprotective benefits if started in the early stages of Parkinson’s.
A study on the MAO-B inhibitor rasagiline1 indicates that people with Parkinson’s who received early treatment had a better outcome than those whose treatment was delayed. It appears that starting soon after diagnosis provides some long term neuroprotection through a compensatory mechanism of the remaining dopaminergic neurons. Further research is needed to understand the compensatory mechanism and how this can be used.
Several studies concerning selegiline, another MAO-B inhibitor, indicate that it too might have neuroprotective actions although more research into this is still needed (DATATOP2).
See also MAO-B inhibitors.
- A randomized, double-blind, placebo-controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale, design, and baseline characteristics - view abstract
- The Parkinson’s Study Group (1993) ‘Effects of Tocopherol and Deprenyl on the Progression of Disability in Parkinson’s Disease’ New England Journal of Medicine; 328: 176–183 - view abstract.
Results of some studies on dopamine agonists, such as the PET/SPECT controlled studies for ropinirole1 and pramipexole2, suggest that they may have some neuroprotective benefits in Parkinson’s. However, not all the studies demonstrate neuroprotective qualities so no clear conclusions can yet be drawn.
The PROUD study3 was the first to combine early versus delayed pramipexole treatment to investigate the potential clinical benefits of early treatment. However, although pramipexole is an effective medication in relieving Parkinson’s symptoms, the results of the study were not conclusive and did not show that early treatment modifies the progression of Parkinson’s.
See also Dopamine agonists.
- Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study - view abstract
- Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression - view abstract
- Rationale for delayed-start study of pramipexole in Parkinson's disease: the PROUD study - view abstract
Vitamin C and E
For some time it has been suggested that the anti-oxidants vitamin C and vitamin E may have some neuroprotective properties in Parkinson’s, although current evidence suggests that the benefits are probably quite small. It appears that the benefits from the vitamins found in natural foodstuffs may not always be derived from the vitamins in dietary supplements1. Further research and studies into this are needed in order to establish any links.
- Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk, Neurology 59(8): 1161–1169 - view abstract
Creatine is a dietary supplement which is often taken by athletes to improve their performance. It is thought that creatine may act as an indirect anti-oxidant by storing energy and protecting against neuronal cell death. Additional studies and research into this are required to better understand if creatine can play a role in neuroprotection.
Coenzyme Q10 (CoQ) is a fat-soluble anti-oxidant compound found in every cell of the body, as well as in a number of foods. Brain levels of CoQ fall with age and are likely to be significantly lower in people with Parkinson’s. Small studies have suggested that CoQ scavenges free-radicals more effectively than vitamin E but further large scale trials using varied dosages are being carried out to establish the true extent, if any, of this compound.
The ELLDOPA1 study assessed the effect of levodopa on the rate of progression of Parkinson’s but the results were conflicting. So the long term effects of levodopa treatment and any possible neuroprotective qualities are still unclear.
See also Levodopa.
- Levodopa and the Progression of Parkinson's Disease (New England Journal of Medicine, volume 351:2498-2508 - 09 December, 2004) - view abstract
Non-steroidal anti-inflammatory drugs (NSAID)
Non-steroidal anti-inflammatory medication, such as ibuprofen and aspirin, are thought to have some neuroprotective benefits. NSAIDs are also naturally present in certain foodstuffs, including turmeric and curcumin. Curcumin is the main active ingredient of turmeric, the most important compound in most curry powders. Like green tea, it belongs to a group of compounds called polyphenols, many of which we now know have health benefits in humans.
Curcumin is the subject of various research studies into its potential benefits, including anti-oxidant and anti-inflammatory properties. These are thought to reduce oxidative damage in the brain, and therefore slow or reverse the progression of Parkinson's, with reduced side effects and toxicity compared to other NSAIDs. It has been estimated that in the US and UK 280 out of 100,000 people develop Parkinson’s whilst in India the rate is as low as 14 per 100,000, leading to speculation that curcumin may be a factor in reducing brain cell damage. Some hypothesise that if turmeric can protect foodstuffs from oxidative degradation, it can perhaps act in a similar way for our bodies, as may other natural NSAIDs. Again, this is an area of ongoing research.
Other potential neuroprotective factors
There are a number of lifestyle choices and nutritional substances that appear to be neuroprotective, such as coffee drinking, cigarette smoking (obviously within sensible limits and with the obvious health caveats) and ginseng. Further studies need to be conducted to establish the extent of any correlation between these and Parkinson’s. It is important to remember that any neuroprotective effect may be quite small and it is generally unwise to consume large quantities of a particular product as this can in itself cause health problems.
Research1 has shown that coffee drinkers who have a daily intake of caffeine of approximately 100 mg, i.e. the amount you might expect in a cup of espresso or a cappuccino, develop Parkinson’s less frequently.
In studies to induce Parkinson’s in animals, caffeine was seen to protect those given the stimulant. A study at the Honolulu Heart Program in Hawaii2 found that the likelihood of developing Parkinson’s was five times greater in men who did not drink coffee compared to those who had at least 28 grams of coffee a day. The men who drank the most coffee had the most reduced risk of developing the condition.
Caffeine is also present in other foodstuffs such as green tea, black tea, chocolate and soda. Consuming these also appears to have a neuroprotective effect.
Whilst research seems to suggest a link between caffeine and Parkinson’s, it is perhaps premature to suggest that caffeine will prevent the condition and it should be remembered that coffee can cause insomnia and anxiety and may affect blood pressure. It could be that the brains of people who like to drink coffee differ from those who do not and that this difference results in the varied incidence of Parkinson’s in relation to coffee consumption.
Polyphenols are naturally occurring anti-oxidants found, for example, in green tea and tangerines. These chemicals act to improve the flow of dopamine between different parts of the brain and could help to slow the loss of dopamine-producing cells. Laboratory studies into polyphenols and Parkinson’s have been carried out in mice, but further studies on tea-drinking in humans are required. It should be noted that over-consumption of green tea can interfere with the absorption of iron by the body and may cause stomach upsets so you should discuss this with your doctor.
Whilst we do not endorse or advocate the smoking of cigarettes because of the many health risks associated with it, studies have consistently suggested a link between cigarette smoking and Parkinson’s, leading to theories that smoking - in particular nicotine - may be neuroprotective. In animal studies nicotine has been found to stimulate the release of dopamine in the brain and to preserve neurons and dopamine levels.
One study3 found that former smokers had a 22% lower risk of developing Parkinson's and current smokers had a 73% lower risk compared to those who had never smoked and were thought to have a ‘normal’ risk for developing the condition. In fact, there appears to be a correlation between the risk of developing Parkinson’s and the number of years of smoking, the number of years since stopping smoking and the number of cigarettes smoked per day.
Ginseng has been used for centuries as a traditional Chinese herbal remedy and today it is widely thought to possess neuroprotective and neurotrophic properties, which may be useful in preventing the degeneration of dopamine-producing cells.
Studies are now underway to better understand if and how ginseng can protect against the condition. In Halifax, Nova Scotia, Canada, in 2004, neuroscientists fed ginseng to rats in their drinking water and then injected them with a powerful toxin MPP+ known to usually induce Parkinson’s in animals. But unusually the rats did not develop the condition, so the researchers concluded that the ginseng had somehow protected their neurons.
Whilst the results are promising, questions remain as to how ginseng works and scientists are trying to establish which components of ginseng have neuroprotective properties so that more powerful medications can be made.
- Leiden University: Coffee and Parkinson's - view abstract
- Association of Coffee and Caffeine Intake With the Risk of Parkinson Disease - view abstract
- Temporal relationship between cigarette smoking and risk of Parkinson disease - view abstract.