Rivastigmine in subcortical vascular dementia: a comparison trial on efficacy and tolerability for 12 months follow‐up

Sir, In the Western world, vascular disease is thought to be the second most common cause of dementia, following Alzheimer's disease (Chui, 1989). It has long been known that cognitive de®cits may result from a stroke, yet only recently have reports demonstrated that dementia may occur in approximately one-fourth to onethird of stroke cases (Tatemichi et al., 1992). It is widely known that the prevalence of all forms of dementia increases with age; in Europe, the prevalence of vascular dementia (VaD) is estimated to be 1.5±4.8% for individuals between the ages of 70 and 80-year-old (Rocca et al., 1991). VaD has heterogeneous forms, amongst the more common are: subcortical VaD caused by small-vessel disease leading to lacunar infarcts and ischemic white matter changes; dementia caused by multiple cortical territorial or watershed infarcts; dementia as a result of single strategic infarcts seated in critical areas (particularly for cognition), such as hippocampus, thalamus and caudate nucleus and ®nally, dementia as a result of intracranial hematomas or mixed forms. Subcortical VaD incorporates the old entities, de®ned as `lacunar states' and is tightly related to small vessel disease and hypoperfusion, resulting in diuse ischemic white matter lesions and incomplete ischemic injury (Erkinjutti, 1987; Pantoni et al., 2000). We studied 16 patients, of both sexes (72.3  4.67 years old) with a diagnosis of probable VaD in complete accordance with NINDS-AIREN criteria (Roman et al., 1993). Brain CT-scans were available for all the patients randomized and reassessed by two neurologist, independently. A patient was de®ned as aected by subcortical VaD when his/her CT scan showed moderate to severe degree of ischemic white matter changes (Erkinjutti, 1997) and one or more lacunar infarct in the absence of non-lacunar territorial infarct and radiological signs of normal pressure hydrocephalus. We decided to divide the patients into two groups: group A, receiving rivastigmine (3±6 mg daily) associated to previously assumed therapy (antihypertensive, antidyslpidemic, antidiabetic drugs) and group B, receiving only cardioaspirin associated to the previously assumed therapy. All the patients were followed for 12 months, with periodical neurological and neuropsychological examinations. Visits were programmed after the ®rst month therapy, after 3, 8 and 12 months from the beginning of the treatment. A complete neuropsychological examination was conducted at the ®rst and at the last visit, and results were compared; during all the visits, we tested selectively some part of cognitive performances, and collected caregiver impression, in order to have a more complete, although not parametric clinical impression of the situation. Our aim was to de®ne if there are modi®cation in cognition, in daily living performance, in behaviour and social conduct, and in relative's stress between the two groups, from baseline situation and after 1 year of therapy. There was no drop out, in both of the groups. Patients were tested with Mini Mental State ± MMSE (Folstein et al., 1975), Ten point clock Drawing test ± TPC (Manos, 1997), Word ̄uency (semantic and phonological) ± WFs and WFp (Wechsler, 1981), Relative Stress Scale (Greene et al., 1982), Instrumental Activity of Daily Living-IADL (Lawton and Brody, 1969), Neuropsychiatric Inventory (Cummings et al., 1994) and with particular attention to new prescription of neurolectics and/or benzodiazepines. At the beginning, there were no dierence between the two groups in all the evaluation. After 1 year of therapy (and the results were also re ̄ected by the clinical impression obtained during the follow-up), group A remained stable in cognition, apart from a slight improvement in TPC test (P < 0.05), but there is an evident trend in reducing the caregiver's stress (RSS; P < 0.05) and a tendency to reduce behavioral discharge (P  0.09). None of the patient needs to assume benzodiazepine, hypnotics or neurolectic. On the contrary, group B demonstrate a trend in deteriorating all cognitive performances, although results were not statistical signi®cant, when compared with their baseline results. But, what strikes attention is that when the two groups are compared, group B TPC results were poorer than group A (P < 0.05), their caregivers resulted more stressed, as stated by RSS results (P < 0.05), their NPI score is higher (P < 0.01) and they have to use dierent sedative or neurolectic (P < 0.05), for social and behavioural alteration. Therefore, in our groups there is a general stable performance in cognitive tasks, with a slight better performances in executive functions, and generally a better behavioural response in the group treated with rivastigmine. Results obtained could be considered limited, because of the few patients enrolled; however, considering that clinical trials performed in patients with VaD have so far achieved unsatisfactory results (Sachdev et al., 1999), and that many drugs have been investigated, but no drug can be positively recommended at present, our data may be stimulating to enrol amore exhaustivenumberofpatients, follow them and try to de®ne an eventual role, for cholinergic drugs in the treatment of vascular cognitive impairment.