synthesis) and indices of cortical pyramidal neurone degeneration (neuronal loss, synapse loss and tangles) correlate with severity of dementia. Note the lack of correlation with the structural marker of cholinergic neurones, ChAT activity. Loss of enzyme exceeded that of acetylcholine synthesis (Sims et al. , 1983a), suggesting a compensatory increase in synthesis in the few remaining neurones. Data derived from Palmer (1987) and Terry et al. (1991). emission tomography (PET) and magnetic resonance, may some day pro­ vide routine insight into differences in brain functioning. Success in developing rapid and reliable diagnostic procedures, perhaps based on changes in body fluid that reflect specific alterations in brain protein metabolism, should ultimately play an important role in the clinical development of new therapeutic agents.