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SUMMARY
Acetyl-L-carnitine (ALC) is a compound acting as an intracellular carrier of acetyl groups across inner mitochondrial membranes. It also appears to have neuroprotective properties and it has recently been shown to reduce attention deficits in patients with Alzheimer's disease (AD) after long-term treatment. We performed an open study to evaluate the effect of ALC (2 g/day orally for 3 months) in association with donepezil or rivastigmine in 23 patients with mild AD who had not responded to treatment with acetylcholinesterase inhibitors (AChE-I). Clinical effects were evaluated by assessing cognitive functions, functional status and behavioural symptoms. The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of ALC, indicating that the combination of these two drugs may be a useful therapeutic option in AD patients. These data do not permit a conclusion as to the possible mechanism of action of the association of the two treatments.
Key words: Acetyl-L-carnitine - Alzheimer's disease - Acetylcholinesterase inhibitors - Therapy
Introduction
Acetylcholine (ACh) is an important neurotransmitter associated with memory, and abnormalities in cholinergic neurones (including cell loss) are among the many neurological and neurochemical abnormalities that develop in Alzheimer's disease (AD)1.
Different strategies have been developed to boost the cholinergic system, including increased acetylcholine production with cholinergic precursors (choline and lecithin), prevention of synaptic acetylcholine destruction with acetylcholinesterase inhibitors (AChE-I), such as tacrine, donepezil, rivastigmine and galantamine, or direct stimulation of postsynaptic muscarinic receptors with receptor agonists2.
The widespread use of AChE-I has demonstrated that only 30-40% of AD patients respond to the treatment, raising the question as to the biological mechanism underlining such different responses. The clinical and social relevance of this phenomenon encourages the search for methods to increase the rate of response to AChE-I treatment, i.e. by combining it with nonpharmacological therapies or with drugs acting with different mechanisms3.
Acetyl-L-carnitine (ALC) is a naturally occurring compound acting as an intracellular carrier of acetyl groups across inner mitochondrial membranes. Several studies indicate that ALC promotes ACh synthesis and release4. In vitro, ALC protects rat cortical neurones from the neurotoxic effects of amyloid fragments and peroxidase (possibly by correcting defects of mitochondrial oxidative metabolism), thus suggesting a potential use of ALC as a neuroprotective agent in neurodegenerative diseases such...