A Systematic Review of Effects of Cholinesterase Inhibitors and Memantine on Cognitive Domains in Alzheimer’s Disease
Anna Williams, Anish Bandalore Satheesha Reddy, Latha VelayudhanBackground
Alzheimer’s Disease (AD) is characterised by progressive cognitive decline. Cholinesterase inhibitors (ChEI) (donepezil, rivastigmine and galantamine) and memantine have been the mainstay treatment and have showed their effectiveness on total cognitive scores, but their effects on individual cognitive domains remain unclear. This systematic review examined their impact on individual cognitive domains.
Method
PubMed, Cochrane, MEDLINE, Web of Science and PsycINFO were searched (1st January 1999 - 31st March 2025) for studies evaluating the effects of ChEI and memantine on cognitive domains using standardised cognitive scales in individuals with AD. The review followed PRISMA guidelines. Risk of bias was assessed using the Cochrane ROB1 tool and a narrative synthesis was used to report the main findings.
Results
Sixteen studies were included. Rivastigmine demonstrated dose-dependent benefits across memory, language, and praxis domains, with higher-doses generally producing less cognitive decline and greater improvements than lower-dose patches or capsules. Donepezil yielded benefits in language, praxis, and visuospatial abilities. Galantamine showed significant improvements in memory, praxis, visuospatial function, and language, and was superior to donepezil in language in one comparative study. Memantine demonstrated benefits across memory, language, praxis, attention, and visuospatial domains, both as monotherapy and as an adjunct to donepezil, with adjunct therapy producing sustained improvements in language and praxis. Overall, higher treatment doses were consistently associated with greater preservation of cognitive function across domains.
Discussion
ChEIs and memantine provide domain-specific cognitive benefits beyond global cognitive improvement. Future studies should examine whether treatment tailored to domain-specific deficits improves patient outcome.
PROSPERO
CRD42024493998.