Prevalence of Fatigue and Associations With Depression and Cognitive Impairment in Patients With CADASIL

Fatigue is a common and disabling symptom in cerebrovascular disease and has been associated with white matter damage, but the underlying disease mechanisms are poorly understood. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic form of stroke and causes a cerebral small vessel disease arteriopathy with white matter ischemia. We determined the prevalence of fatigue in CADASIL, the factors associated with it, and its relationship with both depression and cognitive impairment.

Prospectively recruited genetically confirmed patients with CADASIL were assessed using the Fatigue Severity Scale. The prevalence of fatigue in CADASIL was compared with that of healthy controls from the community. We determined associations between fatigue and clinical features, cardiovascular risk factors, MRI parameters, cognition, and depression. Cognition was measured using the Brief Memory and Executive Test (BMET) and depression using the Geriatric Depression Scale (GDS). Mediation and path analyses were performed to determine relationships between fatigue, depression, and cognitive impairment.

One hundred seventy-four patients with CADASIL (mean age [SD] of 51.3 [12.30] years, 59.66% female) and 50 healthy controls were included in the analysis (mean age [SD] of 51.42 [12.58] years, 38.0% female). Fatigue was present in 51.7% of patients with CADASIL and was almost 5 times more common than in controls (OR: 4.99, 95% CI [2.28-10.95], p < 0.001). There was no association of fatigue with history of stroke or MRI parameters including white matter hyperintensity lesion volume. Logistic regression showed both GDS total score (OR: 1.11 [1.05-1.17], p = 0.0002) and BMET total score (OR: 0.86 [0.75-0.98], p = 0.02) to be predictors of fatigue. Fatigue, depression, and cognition were frequently comorbid. Mediation analysis showed depression to have a greater effect on fatigue prevalence than cognitive impairment. Path analysis confirmed depression to be the largest predictor of fatigue and found this relationship to be bidirectional.

Fatigue was present in over half of the patients with CADASIL. Depression and cognition were the main predictors of fatigue, and all 3 symptoms were frequently comorbid. The relationship between depression and fatigue was the strongest and was bidirectional. This suggests targeting depressive symptoms may have benefit in fatigue management.