NEUROPSYCHOPHYSIOLOGICAL EVALUATION OF 3 DOSES OF S-12024-2 IN MILD-TO-MODERATE ALZHEIMERS-DISEASE

This study was designed to obtain early evidence that S 12024-2 has po tential central pharmacological activity and cognition-enhancing prope rties in patients with Alzheimer's disease (AD). This was a single cen tre, double-blind, crossover study employing three oral doses of S 120 24-2 (50, 100, 200mg once daily) and placebo administered over 7 days (Latin square design). 12 outpatients with mild AD (Mini-Mental State Examination scores 18 to 26) were selected according to the National I nstitute for Neurological and Communication Disorders and Stroke-Alzhe imer's Disease and Related Disorders Association criteria. Clinical an d electrophysiological assessments were used as follows: Clinical asse ssment was performed using: (a) a semicomputerised battery assessing m emory and attention (VDL); (b) the Clinician Interview-Based Impressio n of Change (CIBIC); (c) an Activities of Daily Living scale filled in by the caregiver; Electrophysiological assessment was performed using Quantitative EEG (qEEG) and Event Related Potentials (ERPs). All meas ures at the end of each period (day 7) were compared with baseline mea sures (DO). No statistically significant treatment effect was shown in any clinical assessment. However, the CIBIC showed a trend in favour of active treatment (S 12024-2 100mg >200mg >50mg >placebo). qEEG show ed a significant increase in beta 1 and a decrease in delta activities at 200mg versus placebo (p = 0.01) indicating nonspecific stimulation of diurnal attention. ERPs showed significant treatment activity (p = 0.05) on two parameters: amplitude and latency of the Mismatch Negati vity and the Processing Negativity suggesting an improvement in automa tic processing. In conclusion, the study showed good clinical tolerabi lity of S 12024-2 and preliminary evidence of a central pharmacodynami c activity.