What causes frontotemporal dementia?
Frontotemporal dementia is defined by progressive nerve cell loss, beginning in the frontal lobes – the areas behind your forehead – before spreading to the rest of the brain. It is highly heritable, with genetics thought to be behind a third of all cases.
Paresh Malhotra, a neurology professor at Imperial College London, says that major progress has been made in recent years in terms of understanding the biological basis of frontotemporal dementia. Faulty genes – research has linked mutations in the tau, progranulin and C9ORF72 genes with frontotemporal dementia – result in abnormal protein deposition, which proves toxic to the affected regions of the brain.
“That’s what’s killing the nerve cells in the brain, these abnormal protein deposits,” he says.
Because of this, the charity Alzheimer’s Research UK suggests speaking to your GP if you have a family member who has developed frontotemporal dementia. You may be eligible for genetic counselling and testing on the NHS to see if you carry one of the risk genes for the disease.
Apart from genomic sequencing, there are few clues to suggest that someone might be vulnerable to developing frontotemporal dementia, although neuroscientists suspect that people who display less inhibition and more risk-taking behaviours in their youth might be more predisposed to developing the disease later in life.
“It may be that there’s something about the traits in the genes involved which mean that people have less control in the frontal lobe area, so they did things which maybe weren’t quite right socially,” says Sahakian.
Signs and symptoms of frontotemporal dementia
Willis has reportedly shown signs of cognitive decline for several years. Movie directors discreetly arranged for his dialogue to be shortened and his lines to be fed to him through an earpiece. Last year Willis’s family revealed that he had aphasia – a condition which affects the ability of the patient to speak and write clearly, as well as causing difficulty in understanding written words – prompting him to retire from acting.
Malhotra says that aphasia can be an early indicator of frontotemporal dementia as the disease can damage the temporal lobes of the brain – which are found behind your ears – particularly on the left side, in a similar fashion to a stroke. “They are involved in speech, and they are one of the areas which stop working first,” he says. “And then they start to atrophy or shrink.”
But the most telling sign that someone may be developing the disorder is a sudden and troubling change in personality and behaviour. This can range from depressive symptoms like loss of motivation, to being rude or inappropriate in the presence of strangers.
“One of our patients was found masturbating in his back garden,” says Sahakian. “Another patient was at a dinner party where they saw that their neighbour had a bigger steak, so they reached over, jabbed their fork into it and took it. It’s because our frontal lobes control our inhibitory urges, so once they start to deteriorate, people don’t have that top-down control over their behaviour.”
This makes it quite different to Alzheimer’s disease, where patients retain perfect social behaviour in the early stages, but struggle with memory loss. One of the other distinctions is that people with frontotemporal dementia display rapid shifts in mood, as the disease attacks the serotonergic system that controls emotion regulation.
“It’s a bit like patients who have damage to the frontal lobe from a car accident,” says Sahakian. “You say something to them that’s sad and they start to cry, and you then say something that’s happy and they start to laugh. And they can switch like that very easily, which is not normal.”
What can be done?
At the moment there is sadly no cure for frontotemporal dementia, but doctors can try various approaches to manage the different symptoms.
Speech and language therapy can help patients struggling with aphasia, while Malhotra says that antidepressants can sometimes make a slight difference with the motivation and behavioural symptoms. But the disease is still progressive and none of these medications will stop the ongoing neurodegeneration. “It’s not dealing with the underlying brain disease,” he says.
While the news of Willis’s ailing health is deeply distressing to his legions of fans around the world, there is hope that increased awareness of frontotemporal dementia could help with the ongoing search for a cure.
Our growing understanding of the disease has already led to a number of ongoing clinical trials testing new drugs against various protein targets associated with frontotemporal dementia.
University College London Hospitals NHS Foundation Trust is currently recruiting patients for an international trial – along with hospitals in Australia, Belgium, Spain and the United States – run by Prevail Therapeutics and Eli Lilly. The study is aiming to see whether a novel drug candidate can halt disease progression by reducing the levels of the progranulin protein in the brain.
“There’s been an explosion in our understanding of the groups of conditions that cause frontotemporal dementia,” Malhotra says. “The more we’re understanding about them, the more people are developing new treatments to try and reduce the amount of protein that’s deposited, or perhaps might even be able to clear it.”
