Fatigue was reported in 51.7% of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, according to a recent study.

In the study, published in Neurology, investigators found fatigue was nearly five times more common in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) compared with age-matched healthy controls (odds ratio [OR] = 4.99, 95% confidence interval [CI] = 2.28–10.95, P < .001). They analyzed 174 patients with genetically confirmed CADASIL and 50 controls using the Fatigue Severity Scale, and identified depression as the strongest predictor of fatigue, followed by cognitive impairment.

Logistic regression analysis showed that Geriatric Depression Scale score was associated with a higher likelihood of fatigue (OR = 1.11, 95% CI = 1.05–1.17, P = .0002). Mediation analysis confirmed that depression had a greater effect on fatigue prevalence than cognitive impairment, and path analysis demonstrated that this relationship was bidirectional.

Cognitive impairment, measured using the Brief Memory and Executive Test, was also a significant predictor of fatigue (OR = 0.86, 95% CI = 0.75–0.98, P = .02). While reduced executive functioning and processing speed were linked to depression, orientation and memory impairments had a stronger direct association with fatigue. The findings supported previous research that suggested fatigue may interfere with attention and memory processes, though the underlying mechanisms remain unclear.

Amy A. Jolly, of the Department of Clinical Neurosciences at the University of Cambridge in the United Kingdom, and colleagues further explained that the bidirectional relationship between depression and fatigue "suggests targeting depressive symptoms may have benefit in fatigue management."

However, they also noted that previous research has shown limited efficacy of antidepressants in fatigue treatment.

While past studies have linked fatigue in cerebrovascular disease to white matter damage, the investigators found no statistically significant association between fatigue and brain imaging markers. Comparisons of white matter hyperintensity (WMH) volume, lacune count, and cerebral microbleeds between fatigued and nonfatigued patients with CADASIL showed no statistically significant differences.

Limitations of the study included nonuniformity of equipment used for clinical MRI scans. The researchers suggested that a multidimensional fatigue scale is also needed to capture the many factors that contribute to fatigue.

They concluded that patients with CADASIL experienced fatigue at rates comparable to poststroke populations and emphasized the need for targeted interventions.

The research was funded by the British Heart Foundation Programme Grant and supported by the NIHR Cambridge Biomedical Research Center. No competing interests were disclosed.