Subcortical vascular dementia: Therapeutical aspects

Abstract

Summary A large number of drugs have been or are being currently tested in vascular dementia (VaD) but so far no conclusive evidence has been achieved. Secondary prevention measures, such as control of arterial hypertension and other risk factors, still appear to be the sole approach with some efficacy. Unsuccessful results of trials testing agents aimed at improving the cognitive function and to ameliorate the disease course may stand, at least in part, on the heterogeneity of pathophysiological mechanisms underlying VaD. Therefore, trials testing drugs presumed to be active in VaD should focus on specific pathological subgroups of patients, such as those with subcortical forms. These latter are mainly caused by small intraparenchymal vessel changes leading to focal ischemic damage (lacunar infarcts) in the deep hemisphere structures and to diffuse suffering of subcortical white matter. Calcium-antagonists are drugs that inhibit the intracellular influx of calcium. The alteration of calcium homeostasis is believed to be involved in both cerebral ischemia and aging, hence the possible role of these compounds in the therapy of age-related forms of dementia. The best known calcium-antagonist that crosses the blood-brain barrier and is active in the central nervous system is nimodipine. The rationale for the use of nimodipine in subcortical VaD stems on its action on small vessels. We recently evaluated in a preliminary open trial the efficacy and safety of nimodipine in thirty-one patients with dementia and brain computed tomography images consistent with subcortical VaD. A significant improvement in the total score and in all the items of the San doz clinical assessment geriatric scale (SCAG) was observed throughout the study period. A multi-center, international, randomized, placebo-controlled trial with nimodipine in subcortical VaD is in progress.