Therapeutic trials and Dementia with Lewy bodies: a systematic review of the literature

Geriatr Psychol Neuropsychiatr Vieil. 2021 Dec 16. doi: 10.1684/pnv.2021.0981. Online ahead of print.

Abstract

Background: Cognitive diseases with Lewy bodies occur in two forms: dementia with Lewy bodies (DLB) and Parkinsonian dementia (PD), which follows the evolution of Parkinson disease. There is currently no curative treatment for these cognitive diseases with Lewy bodies. Therapeutic trials in DLB are rare, due to the fact that the disease has only recently been described and the first international diagnostic criteria have only recently been published (1996).

Method: This article proposes a synthesis of the therapeutic trials carried out into DLB in the last five years, including PD patients, using the Clinicaltrials.gov and Pubmed.gov databases.

Results: We identified 35 therapeutic trials on ClinicalTrials.gov and 14 on PubMed. In line with our temporal criteria, 21 trials were analysed. Of the 11 completed trials with reported results, two drugs showed positive results: two trials with zonisamide (phases 2 and 3) showed improvements in Parkinsonian syndrome and one trial with neflamapimod (phase 2) showed improvements in cognition and walking.

Conclusion: In recent years, there has been an increase in therapeutic research into DLB, which is consistent with the prevalence of this disease - approximately 200,000 patients in France. Compared to other cognitive neurodegenerative diseases, therapeutic research is largely insufficient, although the proportion of positive trials is significant. Effective treatment to modify the course of the disease would have significant consequences for patients and their relatives.

Keywords: Clinical trials; Lewy body diseases; Parkinsonian dementia; Pharmacology; dementia with Lewy bodies; α-synuclein.