Pharmacological approaches in the treatment of senile dementia.

The pathogenesis of primary degenerative dementia is still unknown and current therapeutic approaches can aim only at ameliorating some of the symptoms associated with this brain disease. At present, most approaches, attempt to correct a cholinergic deficit. Although the therapeutic benefits obtained so far with currently available cholinergic drugs are generally modest, it appears that there exists a subgroup of responders. This offers some hope that more potent and more selective cholinergic drugs might be more effective. Recent findings suggest that the neurochemical pathology in degenerative dementia is not restricted to the cholinergic system but also includes pathways using monoamines as transmitters. Alternative strategies should therefore include drugs able to correct disturbances in monoaminergic systems. Hydergine and the novel drug CBM 36-733 are suitable candidates. Hydergine is approved by the FDA as being effective for the treatment of selected symptoms of cognitive decline in the elderly. Preliminary results of a 2-month study indicate that CBM 36-733 has beneficial effects in patients with mild to moderate degrees of degenerative dementia. Interestingly, CBM 36-733 also counteracts age-related decreases in choline acetyltransferase, a marker for cholinergic nerve terminals in experimental animals. It will therefore be of interest to clinically evaluate in long-term studies the potential of this drug to slow down the progression of neurodegenerative processes.