Cambridge Study Finds Apathy, Not Depression, Is An Early Sign Of Dementia

Apathy is a reduction in goal-directed behaviour, which is a common neuropsychiatric symptom in SVD.

A new study, led by neuroscientists from the University of Cambridge, has identified apathy as an important early sign of dementia. The research finds apathy is distinct from depression, and offers a more accurate longitudinal association with the onset of dementia.

Cerebral small vessel disease (SVD) is the leading vascular cause of dementia and plays a major role in cognitive decline and mortality. SVD affects the small vessels of the brain, leading to damage in the subcortical grey and white matter. The resulting clinical presentation includes cognitive and neuropsychiatric symptoms.

Apathy is a reduction in goal-directed behaviour, which is a common neuropsychiatric symptom in SVD.

Importantly, apathy is dissociable from depression, another symptom in SVD for which low mood is a predominant manifestation.

Although there is some symptomatic overlap between the two, research using diffusion imaging reported that apathy, but not depression, was associated with white matter network damage in SVD.

Many of the white matter pathways underlying apathy overlap with those related to cognitive impairment, and accordingly apathy, rather than depression, has been associated with cognitive deficits in SVD. These results suggest that apathy and cognitive impairment are symptomatic of prodromal dementia in SVD.

The researchers tested the hypothesis that apathy, but not depression, predicts all-cause dementia using two independent cohorts of SVD patients: the St. George’s Cognition and Neuroimaging Study (SCANS) and Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC).

The researchers had three primary predictions: that baseline apathy, but not depression, predicts dementia after controlling for SVD-related cognitive impairment; that longitudinal changes in apathy, but not depression, would also predict dementia; and that the inclusion of apathy would improve dementia prediction models without apathy.

However, there is still debate over whether the link between depression and dementia is causal. This new research suggests the debate, and discordant data on the topic, may be underpinned by a blurring of the distinction between apathy and depression in many clinical studies.

“There has been a lot of conflicting research on the association between late-life depression and dementia,” says lead author on the study, Jonathan Tay. “Our study suggests that may partially be due to common clinical depression scales not distinguishing between depression and apathy.”

“It is easy to think about apathy as a borderline between laziness and depression,” Di Santo writes, “considering them as a part of the same continuum. It is worthwhile to consider that depression may cause apathy but not all depressed patients are apathetic and not all apathetic patients are depressed.”

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