Patient populations in clinical trials of the efficacy and tolerability of donepezil in patients with vascular dementia.

There is increasing evidence to suggest that patients with vascular dementia (VaD) exhibit a cholinergic deficit. These patients may therefore benefit from treatment with cholinesterase (ChE) inhibitors such as donepezil. However, there are difficulties in accurately defining patients with VaD. Clinical trials to assess the efficacy and tolerability of donepezil in patients with VaD have been completed. National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria were used to establish inclusion and exclusion criteria: evidence of dementia (impaired memory and two other cognitive domains), and evidence of cerebrovascular disease (CVD) from neuroimaging and physical examination and a possible or probable relationship between dementia and CVD were required for enrollment. Patients with a diagnosis of Alzheimer's disease (AD) or dementia caused by other conditions not associated with the cardiovascular system (e.g., MS, chronic infections, hypothyroidism) were excluded. These criteria ensured that only patients with probable or possible VaD were enrolled. Enrolled patients had a mean Hachinski score of 9.7, with memory impairment the most prominent feature of their dementia. Sixty percent of patients had a history of at least one stroke and 18% of patients had a history of transient ischemic attack (TIA) pre-dementia. Cortical and subcortical infarcts were among the lesions observed on computer-assisted tomography and magnetic resonance imaging scans with significant white matter lesions also present in some patients. Placebo-treated patients demonstrated stable cognitive and global function over the 24 weeks of the study. These observations suggest that the patients enrolled in these trials have a broad range of CVD, and are different from those enrolled in AD trials.