Alzheimer disease, attention, and the cholinergic system.

Recent neuropsychological studies suggest that, in addition to prominent mnemonic dysfunction, attentional impairments are a core feature of Alzheimer disease (AD). As is the case for memory, attention is not a unitary process, and only certain components of attention are disrupted in mild AD, particularly sustained and spatial attention. In this article we review evidence from both human and nonhuman neuropsychopharmacology that leads us to suggest that (at least some of) the attentional impairments seen in AD can be related to damage to the basal forebrain cholinergic system (BFCS), in particular the nucleus basalis of Meynert (nbM), which undergoes significant neuronal loss in AD. The BFCS provides the major cholinergic innervation to the cortex and innervates brain regions such as the thalamus, prefrontal cortex, and parietal lobes known to be involved in attentional operations. In addition, studies conducted by our group suggest that drugs acting to stimulate the cholinergic system, in particular tacrine and nicotine, can significantly improve attentional function in patients with AD as measured by improved performance on objective computerised cognitive tasks. Furthermore, cholinergic drugs may also have some utility in other disorders with attentional pathology, such as Parkinson's disease.