A prospective PMS study to validate the sensitivity for change of the D-scale in advanced stages of dementia using the NMDA-antagonist memantine

The present postmarketing surveillance (PMS) study is the first large scale systematic and prospective clinical trial of pharmacotherapeutic intervent ion in advanced stages of dementia. Within a validation program this study aimed at demonstrating the sensitivity of the D-Scale of change (DS-C) for measuring ADL-function. Efficacy of treatment with the NMDA-antagonist mema ntine(1) was investigated in 531 patients with advanced dementia employing a parallel group design that stratified patient cohorts by severity accordi ng to GDS stages (Reisberg, 1992). Efficacy was determined on two independe nt levels: by the assessment of the physicians' Clinical Global Impression of Change (CGI-C) at the end of a 6-week observation period, and by the ass essment of change in elementary ADL-functions by the caregivers using the D -Scale-of-Change. With the D-Scale-of-Change the caregivers can assess a ch ange in broad functional items, i.e. cognitive and motor functions and also elementary functions of daily life. The effect size of this improvement in creased constantly during the observation period. Even in patients of GDS s tage 7 an improvement could be measured. These results were also seen by th e physicians, who recorded an overall clinical improvement in 75.5% of the patients after 6 weeks. Tolerability evaluations resulted in the ratings "v ery well" by 59.5% or "well" by 35.0% of the patients. No serious adverse d rug reactions occurred. A correlation analysis demonstrated a high congruen cy of both assessments. Furthermore, the observed time course of these impr ovements paralleled with the time course of symptomatic benefit by effects of memantine that had been repeatedly demonstrated in randomised, double-bl ind, placebo-controlled studies in mild to moderate dementia. Together with the evaluation of the scale-properties of the D-Scale for assessment of se verity the D-Scale and the D-Scale-of-Change can be regarded as validated.