Relevant clinical outcomes in probable vascular dementia and Alzheimer's disease with cerebrovascular disease

Abstract 

Two important prerequisites for assessing therapeutic benefits in patients with vascular dementia (VaD), or Alzheimer's disease (AD) with cerebrovascular disease (CVD), are the inclusion of appropriate patients and the use of relevant outcome measures. There is substantial overlap in the clinical symptomatology, risk factors, imaging changes, pathophysiology and neurochemical mechanisms between VaD, AD and AD with CVD. While validated and acceptable clinical criteria suitable for clinical trials have been developed for VaD, there is still debate as to how mixed cases (i.e. AD with CVD) are best conceptualized. As with AD, there is consensus that outcome measures in studies of patients with VaD, or AD with CVD, should include assessments of cognitive and global function, of ability to perform activities of daily living (ADL) and of behavioral symptoms. Other measures, e.g., caregiver burden, would be desirable. Care must be taken in extrapolating AD-specific evaluations to VaD, however, because different specific domains are affected and the disease course is different. In clinical trials, cognitive performance and global function decline steadily in patients with untreated AD compared with smaller changes in patients with untreated VaD, while behavior and ADL deteriorate over 6 months in patients with either untreated AD or untreated VaD. Such differences in untreated outcome need to be considered when interpreting trial results using outcome measures that were largely designed for studies of patients with AD.

Keywords:  Vascular dementia, Alzheimer's disease, Cerebrovascular disease, Clinical outcomes, Trial design