Apathy, characterized by a pronounced lack of enthusiasm, motivation, or interest, is a predictor of the future onset of some forms of dementia, say University of Cambridge researchers. These feelings of indifference and detachment occur during a critical “window of opportunity” for commencing clinical interventions during the very early stages of the disease.
“Apathy is one of the most common symptoms in patients with frontotemporal dementia. It is linked to functional decline, decreased quality of life, loss of independence, and poorer survival,” said Maura Malpetti, a neuroscientist from the University of Cambridge and first author of the study.
Frontotemporal dementia is an umbrella term that covers a spectrum of neurological disorders caused by the shrinkage and dysfunction in the brain’s frontal and temporal lobes—regions that control personality, behavior and language. This is one of the leading causes of dementia in younger adults, often diagnosed when they are between 45 and 65. The disease has a strong genetic component, with about a third of patients having a family history of dementia. Frontotemporal dementia can cause dramatic alterations in behavior, leading to uncharacteristic repetitive, impulsive, or socially inappropriate behaviors.
In a study published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, a team led by James Rowe have demonstrated that apathy can start many years before the onset of other behavioral changes, making it a powerful predictor of future problems.
The team followed over 300 healthy adults who tested positive after a genetic screen for the gene that is responsible for frontotemporal dementia, alongside around 300 of their relatives without the gene signature. None of these individuals had been diagnosed with dementia and the majority of them were not aware of their genetic status.
The scientists tracked mood changes, in particular apathy, and also performed a battery of memory tests. They also performed brain scans using MRI.
“By studying people over time, rather than just taking a snapshot, we revealed how even subtle changes in apathy predicted a change in cognition, but not the other way around,” said Malpetti.
"We also saw local brain shrinkage in areas that support motivation and initiative, many years before the expected onset of symptoms.”
Individuals who harbored the genetic mutations associated with dementia indeed experienced apathy significantly more than their healthy family members. This steadily progressed over a period of around two years and culminated with the onset of dementia symptoms.
“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,” explained Rogier Kievit from the MRC Cognition and Brain Sciences Unit at Cambridge.
“At the start, even though the participants with a genetic mutation felt well and had no symptoms, they were showing greater levels of apathy. The amount of apathy predicted cognitive problems in the years ahead.”
As Rowe points out, drawing a line between apathy and dementia is not always straightforward from a clinical perspective. “There are many reasons why someone feels apathetic,” said Rowe.
“It may well be an easy to treat medical condition, such as low levels of thyroid hormone, or a psychiatric illness such as depression. 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.”
Nonetheless, when it comes to dementia treatment, the sooner it can begin, the better. There is a small window of opportunity to maximize the benefits of interventions to slow or stop the progress of this devastating disease. At least now, we know what to look out for.