Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update.

Manuela Pennisi,Giuseppe Lanza,Giulia Malaguarnera,Luisa Vinciguerra,Enzo Vicari,Francesco Fisicaro,Rita Bella,Mariagiovanna Cantone,Emanuele D’Amico,Valentina Puglisi

doi:10.3390/nu12051389

Manuela Pennisi, Giuseppe Lanza + Show 8 more

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https://doi.org/10.3390/nu12051389

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Abstract

Several studies explored the effects of acetyl-L-carnitine (ALC) in dementia, suggesting a role in slowing down cognitive decline. Nevertheless, in 2003 a systematic review concluded there was insufficient evidence to recommend a clinical use, although a meta-analysis in the same year showed a significant advantage for ALC for clinical scales and psychometric tests. Since then, other studies have been published; however, a critical review is still lacking. We provide an update of the studies on ALC in primary and secondary dementia, highlighting the current limitations and translational implications. Overall, the role of ALC in dementia is still under debate. The underlying mechanisms may include restoring of cell membranes and synaptic functioning, enhancing cholinergic activity, promoting mitochondrial energy metabolism, protecting against toxins, and exerting neurotrophic effects. The effects of ALC on the gut–liver–brain axis seem to identify the category of patients in which the new insights contribute most to the mechanisms of action of ALC, likely being the liver metabolism and the improvement of hepatic detoxifying mechanisms the primary targets. In this framework, our research group has dealt with this topic, focusing on the ALC-related cross-talk mechanisms. Further studies with homogeneous sample and longitudinal assessment are needed before a systematic clinical application.

Highlights

We provide an update of the studies on ALC in primary and secondary dementia, highlighting the current limitations and translational implications
Other findings are a widespread loss of neuronal cells and synaptic dysfunction, which might be the result of free radical release and abnormal energy processes
The purpose of this review is to provide an update on the existing literature dealing with ALC effects and tolerability in primary and secondary dementia

Summary

Introduction

Dementia is a common and disabling neurological disorder worldwide. Report of 2015 underlined that over forty-six million individuals across the globe have dementia, with the number expected to rise to over seventy-four million by 2030 and a further increase to over a hundred and thirty-one million individuals by 2050 [1]. Typical clinical features include an acquired impairment of cognitive functions and changes in mood, behavior, and personality, eventually leading to loss of functional independence. Neuropathological findings highlight differences in the existing types of dementia, clinically, memory impairment is observed in most cases and has been linked with the degeneration in cholinergic neurons and reduced levels of brain choline acetyltransferase [2]. Other findings are a widespread loss of neuronal cells and synaptic dysfunction, which might be the result of free radical release and abnormal energy processes

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