Acetyl-cholinesterase-inhibitors reconsidered. A narrative review of post-marketing studies on Alzheimer’s disease

The real efficacy of Acetyl-cholinesterase-inhibitors (AChEI) has been questioned. In this narrative review we evaluated their effect on cognitive decline, measured by Mini Mental State Examination (MMSE), and on total mortality rates in patients with Alzheimer's disease (AD) recruited into post-marketing open/non-randomized/retrospective studies. In AD patients treated with AChEI, the mean MMSE loss ranged from 0.2 to 1.37 points/years, compared with 1.07-3.4 points/years in non-treated patients. Six studies also reported data about survival; a reduction in total mortality relative risk between 27% and 42% was observed, over a period of 2-8 years. The type of studies and the use of MMSE to assess cognitive decline, may have introduced several biases. However, the clinical effects of AChEI seem to be of the same order of magnitude as the drugs currently used in most common chronic disorders, as regards progression of the disease and total mortality. In the absence of long-term randomized trials on "standard" unselected AD outpatients, open/retrospective studies and health databases represent the best available evidence on the possible effect of AChEI in the real-word setting. Our data support the clinical benefit of AChEI in older patients affected by AD.