Cholinesterase inhibitors and vascular dementia: another string to their bow?

Abstract

Two of the four licensed cholinesterase inhibitors, galantamine and donepezil, have recently featured in published work showing how they act in dementia associated with cerebrovascular disease (CVD). It is timely to review this new evidence and place it within the current consensus understanding of what makes up a clearly heterogeneous dementia population. To do this, the current review explores the relationship between Alzheimer's disease, for which this group of compounds originally received licensing approval, and vascular pathology within the brain, highlighting the significant overlap in risk factors and the frequent coexistence of the two conditions in the patients that are studied. Whether they are inter-related or separate entities is discussed, followed by a description of the current classifications of Alzheimer's disease with CVD, and the three subtypes of 'pure' vascular dementia - subcortical, cortical and strategic infarct. Understanding these entities allows more accurate diagnostic and prognostic information to be given to patients, and leads towards matching the published clinical evidence discussed with more predictable clinical syndromes. This distinction is particularly relevant in terms of the studies conducted thus far. Galantamine has been studied in a placebo-controlled study of patients with Alzheimer's disease and CVD as well as patients with vascular dementia, whereas donepezil was studied exclusively in patients with vascular dementia. Differences in the way the placebo groups acted in these studies confirmed the fact that these actually are two distinct groups. Galantamine showed efficacy across the combined groups studied, with placebo deterioration similar to previous Alzheimer's disease studies, while donepezil produced a positive effect in vascular dementia - with this placebo group relatively unchanged. The symptomatic improvements seen were not really surprising, as cholinergic deficits are a common factor across all of these syndromes. Wherever this is the predominant biological finding, it would be expected that cholinesterase inhibitors would have a similar effect, whatever the condition causing it.