Treatment of vascular dementia: evidence from trials with non-cholinergic drugs

A considerable number of therapeutic trials have been performed in vascular dementia (VaD). The results of these trials have generally been considered as disappointing and no drug treatment has been so far approved for the treatment of VaD by regulatory agencies. The aim of the present paper is to critically review the results of randomized clinical trials performed with non-cholinergic drugs in VaD. The conclusions of the present review are that: (1) some drugs such as nicergoline, memantine, posatirelin, propentofylline, and pentoxifylline have shown some, although partly limited, benefits in VaD patients; (2) besides a lack of efficacy of the tested drugs, possible causes of the negative results of many randomized clinical trials in VaD are the enrollment of patients with heterogeneous subtypes of VaD, the small sample size, and the use of end-points and cognitive tests inadequate for the VaD setting because derived from previous experience in the field of Alzheimer disease. Preliminary analyses show that focusing therapeutic trials on specific forms of VaD such as the subcortical type may lead to results different from those obtained in a heterogeneous VaD group. This selective focus seems to be better suited for disclosing specific treatments in the field of VaD.