Acetylcholinesterase inhibitors, neuropsychiatric symptoms, and Alzheimer's disease subtypes: An alternate hypothesis to global cognitive enhancement

Cholinergic neurons are extensively implicated in cognitive functioning. Cholinergic deficiency is a widely accepted hypothesis of cognitive decline in Alzheimer's disease (AD) and is the impetus for the development of cholinesterase inhibitors (ChIs). Studies on the efficacy of ChIs emphasize global cognitive improvement and the amelioration of neuropsychiatric symptoms associated with AD. The authors propose that the current perception of ChIs as global cognitive enhancers may be misleading. It is hypothesized that these drugs improve cognition in specific AD subtypes primarily through psychotropic properties that facilitate attentional processing. In effect, increased attentional capacity through diminished neuropsychiatric symptoms serves to augment results on global cognitive measures: in particular, AD subtypes.