Therapeutic issues in vascular dementia: studies, designs and approaches.

Vascular dementia (VaD) is a heterogeneous disorder resulting from various cerebrovascular diseases (CVD) causing cognitive impairment that reflects severity and location of damage. Epidemiological studies suggest VaD is the second commonest cause of dementia, but autopsy series report that pure VaD is infrequent, while combined CVD and Alzheimer's Disease(AD) is likely the commonest pathological-dementia correlate. Both diseases share vascular risk factors and benefit from their treatment. The most widely used diagnostic criteria for VaD are highly specific but not sensitive. Vascular Cognitive Impairment (VCI) is a dynamic, evolving concept that embraces VaD, Vascular Cognitive Impairment No Dementia (VCIND) and mixed AD and CVD. Clinical trials to date have focused on probable and possible VaD with beneficial effects evident for different drug classes, including cholinergic agents and NMDA agonists. Limitations have included use of cognitive tools suitable for AD that are insensitive to executive dysfunction. Disease heterogeneity has not been adequately controlled and subtypes require further study. Diagnostic VaD criteria now 13 years old need updating. More homogeneous subgroups need to be defined and therapeutically targeted to improve cognitive-behavioural outcomes including optimal control of vascular risk factors. More sensitive testing of executive function outlined in recent VCI Harmonization criteria and longer trial duration are needed to discern meaningful effects. Imaging criteria must be well-defined, with centralized review and standardized protocols. Serial scanning with quantification of tissue atrophy and lesion burden is becoming feasible, and cognitive interventions, including rehabilitation pharmacotherapy, with drugs strategically coupled to cognitive -behavioural treatments, hold promise and need further development.