Meta-analysis of efficacy of cholinesterase inhibitors on individual neuropsychiatric symptoms in Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies.

Meta-analysis of efficacy of cholinesterase inhibitors on individual neuropsychiatric symptoms in Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies.

Alzheimer's disease (AD) is the most prevalent type of dementia, affecting approximately 24 million people globally [1]. It is estimated that Parkinson's disease (PD) and dementia with Lewy bodies (DLB) together affect an additional 10 million people globally (~1.5% of the elderly population [1]). Besides cognitive deficits, such as problems with memory, planning and reasoning, also neuropsychiatric disturbances are an important feature of these diseases. Neuropsychiatric disturbances may result from mental and emotional disorders attributable to the diseases of the nervous system. Examples of neuropsychiatric disturbances are depression, anxiety and hallucinations. Cholinesterase inhibitors (ChEIs), such as donepezil and rivastigmine, form a type of drug that aims to increase communication between certain nerve cells to stabilize or improve dementia symptoms. They have a well established effect on cognitive deficits in the mentioned diseases.By increasing communication between these nerve cells, ChEIs may also have a beneficial effect on neuropsychiatric disturbances. However, this effect is much less clear [2,3]. A possible explanation for the inconsistent results of ChEIs on neuropsychiatric disturbances is that the definition of 'neuropsychiatric' is too broad, as it includes symptoms such as hallucinations and delusions, but also depression, anxiety and irritability, among others.Therefore, we want to conduct a meta-analysis on the efficacy of ChEIs on all individual items of neuropsychiatric outcome measures, to assess which subdomains benefit from treatment and which do not. Individual trials are usually not powered for this subanalysis, which is why we want to pool all the available data.We believe that this meta-analysis will form the basis for a more targeted approach for treating neuropsychiatric symptoms in PD, AD and DLB.However, the beneficial effect on neuropsychiatric disturbances is much less clear [2,3]. A possible explanation for the inconsistent results of ChEIs on neuropsychiatric disturbances is that the definition of 'neuropsychiatric' is too broad, as it includes symptoms such as hallucinations and delusions, but also depression, anxiety and irritability, among others.Therefore, we want to conduct a meta-analysis on the efficacy of ChEIs on all individual items of neuropsychiatric outcome measures, to assess which subdomains benefit from treatment and which do not. Individual trials are usually not powered for this subanalysis, which is why we want to pool all the available data.We believe that this meta-analysis will form the basis for a more targeted approach for treating neuropsychiatric symptoms in PD, AD and DLB.

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d'Angremont E, Begemann MJH, van Laar T, Sommer IEC. Cholinesterase Inhibitors for Treatment of Psychotic Symptoms in Alzheimer Disease and Parkinson Disease: A Meta-analysis. JAMA Neurol. June 26, 2023.
DOI: 10.1001/jamaneurol.2023.1835