Depression and anxiety in vascular dementia: an update.

Depression with a prevalence between 20% and 86% and anxiety with a prevalence up to 72% most frequently coexist with vascular dementia (VaD) and reciprocally increase disease risks. Both psychopathological disorders are usually more frequent and more severe in patients with VaD than in those with Alzheimer disease (AD). Although there is a significant association between depression and all-cause dementia, VaD with depression has more comorbidities and higher mortality than without depression. A history of depression prior to dementia is more common than in AD, while its pre-disease state is a matter of discussion. Although the diagnosis of depression related to cerebrovascular disorders is based on the criteria of DSM-V, VaD/depression has been suggested to be a distinct subtype differing from late-life depression and major depressive disorder, whereas others reported broadly similar depressive symptom profiles across VaD, AD, and AD plus VaD. Depression in the course of VaD, which is frequently underdiagnosed and undertreated, has been related to a variety of pathogenic mechanisms, in particular cerebral small vessel disease (CSVD), cerebral white matter lesions, damage to fronto-subcortical brain circuits, neuroinflammation, impaired neurotrophic support, and imbalance of neurotransmitter/kynurenine pathways. Multimarkers, like high CSVD and white matter hyperintensity burden, the presence of visible perivascular spaces, inflammatory markers, neurofilament light chain levels, and other biomarkers may support clinical diagnosis of VaD/depression. Treatment planning should consider a modest response to antidepressants, while treatment of vascular and metabolic comorbidities may provide promising targets for its prevention and treatment. Electroconvulsive therapy and transcranial direct current stimulation as augmentation treatment of an adequate pharmacotherapy are potential strategies in the management of VaD/depression that is known to be often unresponsive to antidepressants only. However, their effectiveness needs further investigation to assess which interventions are appropriate and effective in clinical practice.