Drug treatments for cognitive impairment due to ageing and disease: Current and future strategies

Abstract

SUMMARYAs the pathological changes in Alzheimer dementia include degeneration of cholinergic neurones, several strategies have been used to enhance the activity of remaining cholinergic neurones, including the administration of anticholinesterases. Other drugs which have been claimed to have a beneficial effect on cognitive impairment in the aged and in various diseases include dihydroergotoxine (the most widely used in clinical practice), bufluomedil, piracetam and centrophenoxine. These drugs, and the many other compounds which have been investigated, have a wide variety of actions. However, drugs which improve the function of neuronal populations affected by pathogenic mechanisms can only be palliative. Future strategies for drug treatments will be directed towards reducing the adverse effects of the ageing process (which may include an increased susceptibility to a range of diseases) and neutralizing the pat'hogenic mechanisms related to genetic factors, infections, toxins, trauma, anoxia and diet. One mechanism which may operate in ageing and in some pathological changes is the production of 'free radicals', which can cause cellular damage. Prophylactic administration of drugs with antioxidant activity can reduce adverse effects of this process in animal models, and such treatments may also protect the brain from the effects of anoxia and other pathogenic mechanisms. Other drugs with therapeutic potential include antagonists of the excitatory effects of glutamate and aspartate.