Achi news desk-
An additional 22 volunteers without Parkinson’s disease were recruited as healthy controls.
Participants were asked to get as many points as possible by choosing between four options.
As the game progressed, the value of each option changed in a similar way to fluctuations in the stock market meaning they had to decide again and again whether to keep or change.
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Those diagnosed with clinical apathy were able to identify the best option but tended to give up early, moving on to another even though it was potentially worse.
In contrast, those without apathy were able to track the best option as well as healthy participants.
When the scientists studied brain activity, they discovered more activity in a “back channel” within the brain among Parkinson’s patients without apathy suggesting that this area is effectively “reprogrammed” to maintain motivation levels.
Dr Tom Gilbertson, who led the study, said: “In the context of apathy in Parkinson’s disease, no one had appreciated before this study that there was another circuit that the brain could use to maintain motivation.
“It’s quite a unique observation.”
Apathy can often be mistaken for depression, but while people with depression may feel pessimistic about their future, those considered apathetic feel apathetic and unmotivated.
Dr Gilbertson, senior clinical lecturer and honorary consultant neurologist at the university’s School of Medicine, said the findings – published in the prestigious medical journal Brain – it could lead to new treatments that significantly improve the quality of life of people living with Parkinson’s disease.
He said: “People with Parkinson’s who develop apathy have a much worse quality of life.
“That includes a greater likelihood of developing dementia and being less likely to respond to treatments which are usually highly effective including surgery.
“They are less motivated by decisions and actions that could lead to rewarding outcomes, which in the real world could see a person less likely to seek social interaction or pursue a hobby they have enjoyed.
“That is because their brain does not incorporate information about what is valuable, and loses its ability to remind a person of what is worth doing to achieve a goal.
“This is the first study to show that the brain, even in an unhealthy state as it is with Parkinson’s, can ignore this loss of this function.
“Understanding the mechanisms behind this compensation could help us develop new treatments aimed at treating or preventing apathy to transform patients’ quality of life.”
The part of the brain that lit up in the non-apathetic Parkinson’s patients connected the thalamus to the prefrontal cortex.
It remains unclear exactly why some patients can produce this response, but Dr Gilbertson believes it could be biochemical.
Other studies have shown that, over time, reductions in hormones associated with the brain’s reward systems – serotonin, noradrenaline, dopamine – accompany apathy beginning with Parkinson’s.
Dr Gilbertson said: “One possibility is that the first thing you lose to some degree is dopamine into the frontal lobe – so that’s the first ‘hit’.
“This other circuit that we have identified may be up-regulated by other neuro-modulators such as serotonin and noradrenaline, and when they are missing – the patients who have had this ‘double hit’ are actually manifests indifference.
“But that is purely speculative at the moment.”
If the theory holds up, Dr Gilbertson said it could open the door to using existing drugs – such as antidepressants – as an early intervention.
He said: “One of the things we’ve started to study is groups of patients in the community who are on SSRIs. [selective serotonin re-uptake inhibitors] to measure their levels of apathy.
“We don’t find much in terms of apathy in those patients and I think one of the treatments for Parkinson’s might be to use drugs that are already available, like [SSRI antidepressant] sertraline, to prevent the progression to apathy.
“If we are correct – and we still have a lot of work to do to prove that it is serotonin that drives this compensation in the brain, and that SSRIs are not bad for apathy – then, possibly , it means we already have. drug out there.
“If you put someone newly diagnosed with Parkinson’s who doesn’t have apathy on something like sertraline, you could delay the progression to apathy in the future.
“That would be great to test in a clinical trial, but we’re still a long way from doing that.”
Another unanswered question is whether preventing or delaying apathy would also slow disease progression and prolong survival.
In PSP – a rarer disease similar to Parkinson’s – the development of apathy has been shown to be highly predictive of how long a patient has to live, suggesting that it has a disease modifying effect.
However, Dr Gilbertson said this was less clear for Parkinson’s disease.
He said: “We don’t know the answer for Parkinson’s. If you can treat apathy in PSP, you may be able to delay death. In Parkinson’s there is no evidence of that.
“But quality of life is very important, which is why everyone is trying so hard to find a better way to prevent it and reverse it if we can.
“The big question for me is whether it’s reversible or not. Maybe once the degenerative process has knocked down all those scaffolding layers. [in the brain] that you cannot reverse.
“But we won’t know until we’ve investigated that.”
