INTRODUCTION

Treatment of cognitive impairment of neurodegenerative diseases has developed late in comparison to treatment of motor impairment. Many reasons apply. Cognitive impairment in Parkinson's disease (PD) has not been regarded as an intrinsic feature of the disease, probably because of Parkinson's original dictum, until relatively recently in the English language literature. Furthermore, also until relatively recently, cognitive impairment has not been studied widely or rigorously enough to permit ready or valid comparisons among investigators. Therapy of cognitive impairment has been neglected perhaps also because it had been indulgently regarded as the universal heritage of age and not as a result of pathological processes which can be compensated, halted or reversed by treatment. While therapeutic nihilism now appears in abeyance, clinical experience has tempered recent enthusiasm.

In this chapter, we offer clinical perspectives of current pharmacological treatment and its effects, intended and otherwise, on cognition and especially memory, in Age-Associated Memory Impairment, Alzheimer's disease (AD) and PD. We speculate about future therapies.

GENERAL PHARMACOLOGICAL PRINCIPLES OF THERAPY

Current pharmacological theory posits that the most specific agents offer the greatest likelihood of efficacy and the least likelihood of adverse effects. To design a highly specific drug requires not only technical knowledge about structure–activity relations, (i.e. molecular structure, biological activity) but also the specific identification of the biochemical defect which is to be corrected by the drug. Development of potent specific agents for dementia (a potentially undifferentiated clinical state) is limited at a crucial juncture by our lack of identification of specific defects which cause dementia. Many (e.g. Growdon 1993) believe that current agents treat dementia epiphenomena poorly and fundamental causes not at all.