Review: Cholinesterase inhibitors do not reduce progression to dementia from mild cognitive impairment

In adults with mild cognitive impairment, what are the efficacy and safety of cholinesterase inhibitors (ChEIs)?

Included studies compared ChEIs (donepezil, rivastigmine, galantamine, or tacrine) with placebo for ≥ 1 month in adults with mild cognitive impairment (as defined by each study but including subjective memory complaint and relatively preserved daily functioning). Primary outcomes were progression to dementia, which included Alzheimer disease (National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria); vascular dementia (consensus criteria); and Lewy body dementia (consensus criteria) assessed at 12, 24, and 36 months; or dementia syndrome (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, or World Health Organization International Statistical Classification of Diseases and Related Health Problems, 10th revision); and adverse events. Secondary outcomes included mortality.

Cochrane Dementia and Cognitive Improvement Group Specialised Register (ALOIS), which includes search results from MEDLINE, EMBASE/Excerpta Medica, CINAHL, PsycINFO, LILACS, trial registers, Cochrane Central Register of Controlled Trials, and gray literature; and reference lists were searched for double-blind, randomized, controlled trials (RCTs). 9 RCTs (n = 5149, age range 45 to 90 y, follow-up range 16 wk to 3 y) met selection criteria. All RCTs had adequate randomization, blinding, and intention-to-treat analysis; 8 were funded by pharmaceutical manufacturers. Donepezil was studied in 3 RCTs, galantamine in 4, and rivastigmine in 2.

The main results are in the Table.

In adults with mild cognitive impairment, cholinesterase inhibitors do not differ from placebo for progression to dementia at 1 and 3 years but increase nonserious adverse events.