ABSTRACT
References 480
Approved treatments for Alzheimer’s disease (AD) target biochemical abnormalities which occur as a consequence of nerve cell loss in forebrain nuclei and in the cerebral cortex. This mode of action addresses the final stretch of a complex pathological cascade (Hardy, 2009) and does not interfere with the mechanisms that induce neuronal degeneration. Cholinesterase inhibitors (ChEIs) partially restore the deficit in acetylcholine which arises from a significant deficit of neurones in the nucleus basalis of Meynert and in the central septal area which project to many cortical regions (Bartus et al., 1982). Memantine attenuates the toxic effects 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 effects has been widely debated, but never demonstrated in human studies (Lleo´ et al., 2006). Cholinesterase inhibitors and memantine may only be used for the treatment of patients with AD diagnosed with dementia. In subjects with subdiagnostic cognitive impairment, ChEIs did not achieve a clinically meaningful delay of progression to dementia (Raschetti et al., 2007). There are no published studies with memantine in this patient population.
