Cholinesterase inhibitors may treat Neuropsychiatric symptoms in Alzheimers and Parkinson's Disease patients: JAMA

Recently Neuropsychiatric symptoms such as depression, apathy, aggression, and psychosis are now recognized as core features of Alzheimer's disease (AD) and Parkinsons Disease (PD), and there is a general consensus that greater symptom severity is predictive of faster cognitive decline, loss of independence, and even shorter survival.

Psychotic symptoms greatly increase the burden of disease for people with neurodegenerative disorders and their caregivers and need for its management has led to several studies recently.

An individual patient data meta-analysis in JAMA Neurology examined the results of treatment with Cholinesterase inhibitors (ChEIs) from 17 randomized clinical trials. The findings of the study suggest that ChEI therapy significantly ameliorates delusions and hallucinations in Alzheimer disease and Parkinson disease.

Researchers performed a systematic in PubMed (MEDLINE), Embase, and PsychInfo, without year restrictions. Studies were selected if they presented the results of placebo-controlled randomized clinical trials, including at least 1 donepezil, rivastigmine, or galantamine treatment arm in patients with AD, PD, or DLB; if they applied at least 1 neuropsychiatric measure including hallucinations and/or delusions; and if a full-text version of the study was available in the English language. Study selection was performed and checked by multiple reviewers.

Primary outcomes were hallucinations and delusions; secondary outcomes included all other individual neuropsychiatric subdomains as well as the total neuropsychiatric score.

The key findings of the study are

• In total, 34 eligible randomized clinical trials were selected. Individual participant data on 6649 individuals (3830 [62.6%] women; mean [SD] age, 75.0 [8.2] years) were obtained from 17 trials (AD: n = 12; PD: n = 5).

• An association with ChEI treatment was shown in the AD subgroup for delusions (−0.08; 95% CI, −0.14 to −0.03; P = .006) and hallucinations (−0.09; 95% CI, −0.14 to −0.04; P = .003) and in the PD subgroup for delusions (−0.14; 95% CI, −0.26 to −0.01; P = .04) and hallucinations (−0.08, 95% CI −0.13 to −0.03; P = .01).

The researchers concluded that “The results of this individual participant data meta-analysis suggest that ChEI treatment improves psychotic symptoms in patients with AD and PD with small effect sizes.”

Reference: 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. Published online June 26, 2023. doi:10.1001/jamaneurol.2023.1835.