Can Parkinson's drug help old people decide?
“Parkinson's drug 'helps' the elderly think younger and reap the rewards from the choices they make,” according to the Mail Online. It reports that as you age you lose the ability to learn from experiences, which can lead to poor decision making. But the drug levodopa, used to treat Parkinson’s disease, could help the elderly to think again in a ‘younger manner’, it says.
Researchers speculate that the lower levels of dopamine found as people grow older could be harmful to the part of the brain that judges whether choices lead to beneficial rewards. Levodopa can increase levels of dopamine, so researchers wanted to see if it improved decision making skills.
In this study, a small group of older people performed tasks where making the correct decision could win them money. The researchers then looked at the effect that dopamine treatment had on their performance. They also compared the performance of these older adults with 22 healthy young adults.
They found that half of the older people improved performance with levodopa, but there was no improvement in the other half.
The research doesn’t tell us much more than how ageing may affect the chemical processes of the brain. Levodopa is only licensed for use in Parkinson’s conditions. Given the side effects of the drug, and that in this small study it only gave some benefit to half the participants, it is very unlikely that its use would ever be extended to all older adults, simply to boost decision making.
Where did the story come from?
The study was carried out by researchers from University College London and other institutions in the UK and Europe. Funding was provided by the Wellcome Trust.
The study was published in the peer-reviewed Nature Neuroscience.
Overall, the Mail Online’s reporting takes this small scientific research study a step too far, suggesting that the Parkinson’s drug can be used to treat older adults to help improve their decision making. This was scientific research exploring the chemical processes in the brain and how they may affect decision making, but it certainly has no therapeutic implications. Levodopa is licensed only for the treatment of Parkinson’s disease and related conditions.
Even if the medication was found to be effective (which is unproven by this study) it is unlikely it would be used simply to aid decision making, as the small benefits of the drug are unlikely to outweigh the risks. Most people would be unwilling to tolerate the side effects that can occur after levodopa use, such as nausea, vomiting, tiredness and dizziness.
What kind of research was this?
The researchers’ report that older adults are worse at making decisions when there are outcomes with different probability of reward led them to question what accounts for this poor decision making. Evidence from previous human and animal study suggests that an area of the middle of the brain, called the nucleus accumbens, has a key role in any decisions that may involve the likelihood of potential rewards and pleasurable emotions.
The nucleus accumbens is targeted by the chemical dopamine. Previous studies of brain samples of older adults have shown that there is a loss of dopamine nerve cells in certain areas of the brain that increases with age. So the reduction in dopamine levels and the subsequent effects on the nucleus accumbens may be responsible for the poorer reward-based decision making associated with ageing.
The current research used a sample of healthy older adults and gave them a task where they had two choices. At the same time they had functional magnetic resonance images (fMRI) taken, which measures the blood flow in the brain to show what areas of the brain are active.
They also had another special type of MRI scan called diffusion tensor imaging (DTI), which can identify any areas of the brain that are lacking oxygen. For this reason DTI is useful for examining people who have had a stroke, but also is a good technique for looking at conditions involving the nerve fibres (white matter).
The researchers compared the results for the older adults with the results from a sample of adults in their 20s. They also examined the effect of a placebo or the chemical levadopa (L-dopa - which is converted to dopamine in the brain and used in the treatment of Parkinson’s disease) on the older adults’ performance in the tasks.
What did the research involve?
The study involved 32 healthy adults aged 65-75 years. These people attended the study centre on two occasions, one week apart, and performed the same task on both occasions. They were randomised to receive in random order either placebo or L-dopa (both mixed into an orange juice drink).
Participants performed five practise trials of the two-armed bandit task before performing the same task before placebo or L-dopa. The task involved being shown two images, selecting one of these and being shown what the monetary reward of this image was. They used statistical tests to compare task performance (how much money was won) under L-dopa or placebo, in addition to monitoring brain activity using fMRI and DTI. Participants were also monitored for any adverse effects of the drugs.
They also compared the performance of the older adults with 22 healthy young adults (average age 25 years) who performed the tasks without taking L-dopa or placebo.
What were the basic results?
The researchers found that the older adults had similar choice reaction times after taking L-dopa and placebo, but overall they had slower reaction times than the younger participants.
Overall there was also no significant difference in the amount of money won by the older participants when L-dopa was given compared to placebo. Fifteen older people won more money with L-dopa than placebo, and 17 won less with L-dopa than placebo. When they analysed in more detail the differences between these two groups they found that those with lower baseline task performance with no treatment (on placebo) improved when they were given L-dopa. However, those older adults who had higher baseline performance with no treatment did not improve with L-dopa.
Those older participants who improved with L-dopa then had similar task performance to the younger participants. Those who did not improve with L-dopa had similar task performance to the younger participants without treatment.
Of those who won more on L-dopa, L-dopa appeared to be improving their learning behaviour with successive tasks. Meanwhile, in those who did not perform better with L-dopa, the drug did not seem to be having any effect on their learning behaviour.
Looking at the fMRI images, the researchers found that older adults had less of a ‘reward prediction error’ signal in the nucleus accumbens. This reward prediction error is thought to be a spike in dopamine levels that occurs when the brain experiences an unexpected reward.
Using DTI to look at the dopamine nerves supplying the nucleus accumbens, they found that within individuals, the structure of their nerve connections was related to whether they had an RPE signal. In older adults with poorer nerve connections, giving L-dopa restored the RPE signal.
Four of the 32 older participants experienced vomiting a few hours after taking L-dopa, but they were still to take part in the tasks before experiencing this side effect.
How did the researchers interpret the results?
The researchers conclude that their results identify that chemical signalling problems in the dopamine nerves underlie the abnormal reward processing in older adults, and suggest that this problem can be modulated by the drug L-dopa.
Conclusion
Overall, this research is of scientific interest – it furthers our understanding how ageing may affect the chemical processes of the brain. Specifically it suggests that the reason our ability to make rewards-based choices declines as we age may, in part, be related to poor dopamine signalling to the nucleus accumbens.
However, this small study in 32 older adults tells us little more than that.
These older adults were healthy and were not reported to be suffering from any cognitive impairment. Their results cannot be generalised to all older adults, and not to those who may be suffering from neurodegenerative conditions such as Alzheimer’s disease.
While levodopa has been hailed by the media as a solution for making better decisions in older age, the drug is currently licensed only for conditions related to Parkinson’s disease. It is associated with adverse effects and would not be suitable for everyone.
It should be noted that taking levodopa did not actually improve the decision-making ability of everyone – for half the older adults who had similar decision making ability to younger participants, taking levadopa reduced their decision making ability instead.
It is highly unlikely that this will ever be offered as a treatment for every person over a particular age to preserve their decision making ability.
Overall, this research has no immediate implications for the prevention or treatment of cognitive decline or dementia in older adults.
