Apathy May Be An Early Predictor Of Dementia Years Before Other Symptoms Show

We all have days where we struggle to get out of bed. But everyday laziness should not be mistaken for apathy – a disabling lack of interest, emotion, or motivation – which new research suggests could be an early marker of dementia in at-risk families.

Following 600 people for two years, a new study has found apathy occurred early, worsened over time, and predicted a decline in brain function in people who had inherited a genetic risk of dementia but were otherwise healthy.

There are many forms of dementia, which is an umbrella term for a collection of symptoms caused by brain disorders.

Though all forms are debilitating, and Alzheimer's disease is the most common, this study focuses on just one: frontotemporal dementia (FTD), which is often diagnosed between 45 and 65 years of age.

Dementia, collectively, affects around 50 million people worldwide, and the risk factors are well known: age is number one, plus poor heart health and physical inactivity, particularly in mid-life, can raise your risk.

But recognising when dementia takes hold remains a great challenge. Much research is focused squarely on understanding how dementia develops in its early stages – looking for the emergence of its first subtle symptoms, which can vary.

Finding early warning signs of dementia means doctors and families would have a chance to intervene, not yet with a prevention or cure, but to help people get the supportive care they need, if and when they are diagnosed with the condition.

It could also be used to improve the design of clinical trials recruiting people with early dementia.

"From other research, we know that in patients with frontotemporal dementia, apathy is a bad sign in terms of independent living and survival," said clinical neuroscientist James Rowe from the University of Cambridge.

"Here we show its importance in the decades before symptoms begin."

Apathy is a common feature of FTD, amongst other symptoms such as unusual changes in mood and behaviour, difficulty making good judgements, and impulsiveness.

In this study, people at risk of developing FTD showed signs of apathy years before doctors expected to see other symptoms, based on their age.

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"We also saw local brain shrinkage in areas that support motivation and initiative, many years before the expected onset of symptoms," said Maura Malpetti, a cognitive neuroscientist at the University of Cambridge.

The link between shrinkage of the brain, called atrophy, and apathy has been established before in people showing symptoms of FTD.

What's new here is tracking apathy from when it first arises in people at risk genetically of FTD, but who have no other symptoms and are otherwise healthy, to see if apathy predicts the onset of dementia and the cognitive decline that follows.

In this study, some 300 people carrying a faulty gene that causes FTD – and roughly the same number of their relatives (who lacked any gene fault) – were recruited through the Genetic Frontotemporal dementia Initiative, a research collective studying families affected by FTD.

People were assessed three times over two years, with brain scans, measures of apathy, and tests for cognitive function, including memory.

"At the start, even though the participants with a genetic mutation felt well and had no symptoms, they were showing greater levels of apathy [than their unaffected relatives]," said Rogier Kievit, another University of Cambridge cognitive neuroscientist involved in the study.

"The amount of apathy [at baseline also] predicted cognitive problems in the years ahead."

The researchers observed how apathy worsened among FTD gene carriers and their cognitive abilities deteriorated over two years, more so than other family members in the study and more severely in older participants.

"Apathy progresses much faster for those individuals who we know are at greater risk of developing frontotemporal dementia, and this is linked to greater atrophy in the brain," Kievit said.

All this might sound promising, that apathy could predict dementia onset, but remember, the study specifically looked at apathy in people with an identifiable genetic risk factor for FTD, and no other forms of dementia, and not in the general population.

Also, no one symptom alone indicates dementia.

It can also be tricky to distinguish apathy from depression, another symptom of dementia and condition marked by low energy. To avoid confusion, the researchers in this study used two different validated tools to measure apathy and depression separately.

But there are also other unrelated causes of apathy, such as hormone deficiencies, which shouldn't be overlooked, as the researchers acknowledged.

"There are many reasons why someone feels apathetic… But doctors need to keep in mind the possibility of apathy heralding a dementia, and increasing the chance of dementia if left unaddressed, particularly if someone has a family history of dementia," said Rowe.

"Treating dementia is a challenge, but the sooner we can diagnose the disease, the greater our window of opportunity to try and intervene and slow or stop its progress."

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