The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well established. Randomised trials have shown them to be associated with a reduction in the rate of cognitive decline. Exploring how well these drugs perform in a real world scenario, Nemanja Vaci et al have shown that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate. The study was recently published in The British Journal of Psychiatry.
The evidence for cholinergic loss in dementia that correlates with severity of disease led to the development inhibitors of the enzyme acetylcholinesterase. Three acetylcholinesterase inhibitor (AChEI) agents have been approved (donepezil, rivastigmine and galantamine) for the treatment of mild to moderate forms of Alzheimer's disease.
Memantine is the fourth available option which is thought to counteract some of the neurotoxicity in Alzheimer's disease through antagonism of the glutamate N-methyl-D-aspartate (NMDA) receptor. In contrast to AChEIs, memantine is approved for the treatment of the more advanced forms of Alzheimer's disease.
In this study relevant medications information was extracted and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10 year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling.
The results of this study can be summarised as following:
1. The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated.
2. Medication prescription stabilises cognitive performance for the ensuing 2–5 months.
3. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics.
4. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment.
This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. It was found that more than two-third individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate.
Source: The British Journal of Psychiatry: doi: 10.1192/bjp.2020.136