Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review

Abstract

The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as dementia, deserves deep investigation for the detection of novel disease-modifying approaches. Several drugs belonging to different classes were suggested to be effective in managing Alzheimer’s disease (AD) by means of autophagy induction. Useful autophagy inducers in AD should be endowed with a direct, measurable effect on autophagy, have a safe tolerability profile, and have the capability to cross the blood–brain barrier, at least with poor penetration. According to the PRISMA 2020 recommendations, we propose here a systematic review to appraise the measurable effectiveness of autophagy inducers in the improvement of cognitive decline and neuropsychiatric symptoms in clinical trials and retrospective studies. The systematic search retrieved 3067 records, 10 of which met the eligibility criteria. The outcomes most influenced by the treatment were cognition and executive functioning, pointing at a role for metformin, resveratrol, masitinib and TPI-287, with an overall tolerable safety profile. Differences in sample power, intervention, patients enrolled, assessment, and measure of outcomes prevents generalization of results. Moreover, the domain of behavioral symptoms was found to be less investigated, thus prompting new prospective studies with homogeneous design. PROSPERO registration: CRD42023393456.

Basic, Translational, and Clinical Research on Dementia

“…Useful autophagy inducers in AD should be endowed with a direct, measurable effect on autophagy, have a safe tolerability profile, and have the capability to cross the BBB, at least with poor penetration. According to the PRISMA 2020 recommendations, Corasaniti et al [38] have conducted a systematic review to appraise the measurable effectiveness of autophagy inducers in the improvement of cognitive decline and neuropsychiatric symptoms in clinical trials and retrospective studies. The outcomes most influenced by the treatment were cognition and executive functioning, pointing at a role for metformin, resveratrol, masitinib and TPI-287, with an overall tolerable safety profile.…”

“…Differences in sample power, intervention, patients enrolled, assessment, and measure of outcomes prevent the generalization of results. Moreover, the domain of behavioral or neuropsychiatric symptoms has been found to be less investigated, thus prompting new prospective studies with homogeneous design [38] since the latter affect some 99% of patients over the course of the disease [39] and they are managed with potentially harmful antipsychotics [40]. Belardo et al [41] have attempted a preclinical approach to the development of novel non-pharmacological control of AD and associated neuropsychiatric symptoms.…”