Alzheimer's dementia is associated with the loss of cholinergic neurons, specialised brain cells that produce an important messenger protein called acetylcholine. Acetylcholinesterase inhibitors (ChEI) like Donepezil constitute one of the two main classes of approved drugs for the treatment of Alzheimer's dementia, and work by maximising the availability of acetylcholine in the brain. Whether ChEI drugs have a substantial effect on cognition is a hotly-contested topic. In addition, few studies have addressed the question of whether ChEI are beneficial for people with Alzheimer's dementia in the long term.
In this study, recently published in the Neurology journal, a team of researchers led by Prof. Maria Eriksdottir (Karolinska Institute, Sweden) set out to investigate whether the long-term use of ChEI is associated with slower cognitive decline, decreased severity and death in Alzheimer's dementia. Analysing data from over 17,000 participants in the Swedish Dementia Registry (SveDem) study, the researchers evaluated the cognitive and clinical outcomes of 11,652 people who had started using ChEI within 3 months of diagnosis, compared with 5,862 non-users of ChEI. Over an average of 5 years, 255 people progressed to severe dementia, and over 6,000 died. Statistical analyses showed that people with Alzheimer's dementia who used ChEI had slightly higher cognitive test (MMSE) scores than those who didn't use ChEI, equivalent to an average increase of 0.13 points/year. Use of ChEI was associated with a 27% reduction in mortality, with Galantamine having the strongest effects on cognitive decline and death. Of the three ChEI studied (donepezil, rivastigmine and galantamine), only galantamine significantly reduced the risk of developing severe dementia.
https://n.neurology.org/content/early/2021/03/19/WNL.0000000000011832