Summary: In older adults with cerebral small vessel disease (SVD), higher levels of apathy at baseline and increases in apathy over time were linked to a greater risk of developing dementia. By contrast, baseline depression and increases in depressive symptoms did not show a clear association with later dementia diagnoses.
Source: University of Cambridge
Apathy, not depression, appears to be a meaningful early indicator of dementia in people with cerebrovascular small vessel disease, according to new research led by the University of Cambridge.
While late-life depression has often been considered a potential risk factor for dementia, this study suggests that previous findings may have been confounded by measurement tools that do not clearly separate apathy from depressive symptoms. Researchers from the universities of Cambridge, King’s College London, Radboud, and Oxford examined whether apathy or depression better predicts dementia among patients with cerebral small vessel disease.
Published on 11 July in the Journal of Neurology, Neurosurgery & Psychiatry, this is the first study to directly compare apathy and depression as predictors of dementia in SVD. Cerebral small vessel disease affects about one in three older adults, contributes to roughly a quarter of strokes, and is the most common vascular cause of dementia.
The research analyzed two independent cohorts of patients with MRI-confirmed SVD—one from the UK and one from the Netherlands. Across both groups, people with higher apathy scores at the start of the study, and those whose apathy increased over time, had a higher likelihood of progressing to dementia. Conversely, neither initial depression levels nor changes in depression scores were associated with dementia risk.
These relationships held true even after accounting for established dementia risk factors, including age, education, and baseline cognitive performance, and despite differences in symptom severity between the cohorts. That consistency suggests the findings may be generalizable across a broad range of SVD cases.
Lead author Jonathan Tay of the Department of Clinical Neurosciences at the University of Cambridge commented that inconsistent results in previous studies linking depression to dementia could reflect the conflation of apathy and depression on some clinical rating scales. He emphasized that distinguishing these conditions is important for accurate risk assessment.
Apathy—characterized by diminished motivation and reduced goal-directed behavior—is a common neuropsychiatric feature of SVD and is distinct from depression, although the two can overlap symptomatically. Prior MRI research has linked apathy, but not depression, to disruption in white matter networks, which are critical for motivation and cognitive function in SVD.
Tay suggests that tracking apathy over time could provide clinicians with an early signal of increasing dementia risk. Patients identified with persistently high apathy or with notable increases in apathy could be prioritized for more detailed clinical assessment, monitoring, or targeted interventions.
The study included more than 450 participants with MRI-confirmed SVD, recruited from three hospitals in South London and Radboud University Medical Center in the Netherlands. All participants underwent repeated assessments of apathy, depression, and cognitive status over several years.
In the UK cohort, nearly 20% of participants progressed to dementia during follow-up, compared with 11% in the Dutch cohort—a difference likely reflecting a higher burden of SVD in the UK sample. In both cohorts, people who later developed dementia had higher baseline apathy but similar baseline depression levels compared with those who did not develop dementia.
The findings support further investigation into the mechanisms linking apathy, vascular cognitive impairment, and dementia. Recent neuroimaging work points to overlapping white matter networks that support both motivation and cognitive processes; damage to these networks from cerebrovascular disease—often related to hypertension or diabetes—may produce early motivational and cognitive changes that progress to dementia as the pathology advances.
Tay notes that apathy likely represents an early symptom of underlying white matter network damage rather than an independent causal risk factor for dementia. Better understanding and measurement of apathy could therefore improve early identification of patients at risk and guide clinical decision-making.
About this dementia research article
Source: University of Cambridge
Media Contact: Tom Almeroth-Williams – University of Cambridge
Image Source: Public domain image.
Original Research: Open access. DOI: 10.1136/jnnp-2020-323092 — “Apathy, but not depression, predicts all-cause dementia in cerebral small vessel disease” by J. Tay et al., Journal of Neurology, Neurosurgery & Psychiatry.
Abstract
Apathy, but not depression, predicts all-cause dementia in cerebral small vessel disease
Objective
To determine whether apathy or depression better predicts all-cause dementia in patients with cerebral small vessel disease.
Methods
Analyses combined data from two prospective SVD cohorts: St. George’s Cognition and Neuroimaging in Stroke (SCANS; n=121) and the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC; n=352). Multivariate Cox regression models examined whether baseline apathy and depression scores predicted dementia in both datasets. Change in apathy and depression over time was evaluated in a longitudinal SCANS subset (n=104). All models adjusted for age, education, and cognitive function.
Results
Baseline apathy predicted dementia in SCANS (HR 1.49, 95% CI 1.05 to 2.11, p=0.024) and RUN DMC (HR 1.05, 95% CI 1.01 to 1.09, p=0.007). Increasing apathy over time was associated with dementia in SCANS (HR 1.53, 95% CI 1.08 to 2.17, p=0.017). By contrast, baseline depression and changes in depression did not predict dementia in either cohort. Including apathy in predictive models improved model performance.
Conclusions
Apathy, but not depression, may serve as a prodromal symptom of dementia in SVD and could help identify individuals at increased risk for progression to dementia.