ABSTRACT
Approved treatments for Alzheimer’s disease (AD) target biochemical abnormalities, which are a consequence of nerve cell loss in forebrain nuclei and in the cerebral cortex. eir mode of action thus addresses the nal stretch of a complex pathological cascade (Hardy, 2009) but does not interfere with the mechanisms that induce neuronal degeneration. Cholinesterase inhibitors (ChEIs) partially restore the decit in acetylcholine, which arises from a signicant decit of neurones in the nucleus basalis of Meynert and in the central septal area, both of which project to cortical regions (Bartus et al., 1982). Memantine attenuates the toxic eects of glutamate, which is released in excess from degenerating cortical neurones, but preserves physiological glutamate-mediated signalling (Greenamyre et al., 1988). Whether these therapies confer additional neuroprotective potential in addition to purely symptomatic eects, has been widely debated, but has not been demonstrated in human studies (Lleó et al., 2006). ChEIs and memantine may only be used for the treatment of patients with AD diagnosed with dementia. In subjects with pre-dementia AD, ChEIs did not achieve a clinically meaningful slowing of progression in the disease (Raschetti et al., 2007). e potential of memantine for the secondary prevention of dementia has not been explored.
