An open-label pilot study comparing rivastigmine and low-dose aspirin for the treatment of symptoms specific to patients with subcortical vascular dementia

Abstract

Background: Patients with vascular dementia (VaD) show cholinergic deficits that may result in characteristic clinical syndromes for different subtypes of the condition. In addition to executive function, subcortical VaD is characterized by behavioral and emotional problems, reflecting deterioration of the frontal lobe. Objective: The purpose of this study was to determine the effect of rivastigmine on the specific symptoms of subcortical VaD. Methods: Patients received rivastigmine 3 to 6 mg/d (n = 8) or low-dose aspirin (cardioaspirin) 100 mg/d (n = 8) for 22 months in an open-label study design. Rivastigmine-treated patients began therapy with the lower dosage of rivastigmine 3 mg/d, which was increased to the higher dosage of 6 mg/d after 4 weeks. Disease severity was assessed using the Clinical Insight Rating Scale. Behavior was assessed using the NeuroPsychiatric Inventory (NPI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Cornell Scale for Depression in Dementia (CSDD). The main results of this study, including executive function, NPI, and caregiver stress scores, have been presented elsewhere. Results: Sixteen patients were enrolled. Patients receiving rivastigmine showed statistically significant improvements in their BEHAVE-AD and CSDD scores ( P = 0.001 and P = 0.02, respectively, versus cardioaspirin). Comparison of individual items on the BEHAVE-AD scores of the rivastigmine group with the cardioaspirin group indicated statistically significant improvements in activity disturbance, affective disturbance, aggressiveness, anxiety/phobia, hallucinations, and paranoia/delusions ( P = 0.007, P = 0.035, P = 0.008, P = 0.003, P = 0.006, and P = 0.001, respectively). Similarly, comparison of the NPI scores of the 2 groups showed that the rivastigmine group experienced significantly greater improvements in anxiety, hallucinations, and wandering ( P = 0.001, P = 0.005, and P = 0.014, respectively). Side effects in both groups were tolerable and there were no study withdrawals. Conclusions: In this preliminary study, rivastigmine treatment was well tolerated and effective. Improvements in the symptoms that characterize subcortical VaD were observed, suggesting that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population. A large, double-blind, placebo-controlled study of rivastigmine in patients with VaD is warranted.