White Matter Changes in Brain May Be Marker of Apathy in Patients, Study Says

The severity of small vessel disease in the brains of Parkinson’s disease patients is significantly associated with apathy, and may serves as a marker to predict its progression in these people, a recent study found.

It might also be useful in distinguishing apathy from depression, which have similar clinical manifestations.

The study, “White matter hyperintensities: a marker for apathy in Parkinson’s disease without dementia?,” was published in Annals of Clinical and Translational Neurology.

Apathy, which describes a lack of interest, enthusiasm, or motivation, is a common non-motor manifestation of Parkinson’s disease and one that significantly affects quality of life. Apathetic patients are less inclined to follow their medication schedules or to participate in beneficial activities, like exercise and social interaction.

While often accompanied by depression, apathy is not the same as depression. Yet, effective markers that help to distinguish one from the other are  lacking. Factors predicting apathy and its progression in Parkinson’s patients are also not well known.

Changes in the brain’s white matter, made up of nerve fibers, have been linked to apathy in recent studies. But the magnetic resonance imaging (MRI) methods used in these studies are often not available at clinics monitoring Parkinson’s patients. Researchers at Shanghai Jiao Tong University School of Medicine in China investigated whether more common MRI scans could be used instead.

They focused particularly on white matter hyperintensities (WMH), which are small vessel lesions in the brain that show up with increased brightness on MRI scans. The severity and location of these lesions can be easily measured with the Fazekas visual scale.

Their study included 141 patients without dementia, recruited from the Department of Neurology at Xin Hua Hospital from December 2014 to April 2017. At study start, patients were assessed for multiple motor and non-motor symptoms, including WMH severity and location, as well as apathy. Apathy was again assessed 2.5 years later.

Apathy was scored using the Lille apathy rating scale (LARS), a semistructured interview that provides a global score of apathy, as well as subscores for its different domains, including cognition, behavior, and self-awareness. Those with scores above –7 are considered to be apathetic.

Overall, 68 patients were identified as having apathy and 73 as not. These two groups were generally similar in terms of age at disease onset, disease duration, cognitive impairment, medication use, initial symptom presentation, wearing off, and sleep problems.

However, the apathy group included significantly more males, had worse motor symptoms, higher depression scores, worse non-motor symptom scores, and their daily life activities were more affected by the disease. Fazekas scores of white matter hyperintensities were also higher in this group, suggesting greater WMH severity.

Statistical analysis showed that WMH severity was significantly associated with apathy, but not depression, in these patients. The location of WMH, however, was not associated with either apathy or depression.

Notably, the association between WMH severity and apathy remained after accounting for multiple confounding factors, including sex, age, age at disease onset, disease duration, educational level, smoking and alcohol consumption, initial symptoms, medication, and severity of motor symptoms. No association was found between WMH severity and depression after accounting for the same factors.

After 2.5 years of follow-up, 70 patients showed progression in their apathy, and 71 were stable or showed lesser apathy. Compared with those who had no worsening in apathy, progressors were generally older, had developed the disease at later ages, and had greater WMH severity at baseline.

Researchers again found an association between WMH severity at a study’s start and apathy: the greater the WMH severity, the faster apathy progressed. This association was kept after accounting for a number of confounding factors.

The team also found that a score of 3 or greater on the WMH Fazekas scale could be used to diagnose apathy in patients, without yielding false positives. “Such a tool would be extremely useful for differentiating apathy from depression to facilitate better clinical management,” the team wrote.

These findings also shed some light on the disease processes of apathy, which appears to be “tied to organic factors, especially cerebral small vessel factors, while depression is not.”

Overall, the study shows that “WMH severity may be a suitable marker for diagnosing and monitoring apathy. We recommend its regular use in screening for apathy in PD [Parkinson’s] patients that do not exhibit signs of dementia,” the researchers wrote.

“Our results also suggest that cerebral small vessel disease may be at least part of the cause of apathy in PD and may represent a future therapeutic target,” they concluded.