Acetyl-l-carnitine for dementia: Cochrane systematic review
Assessed as up to date: 2007/11/07
Dementia is a common mental health problem affecting 5% of those over 65. Various pathological processes are linked to memory impairment in dementia, particularly those affecting the cholinergic neurotransmitter system. Acetyl-l-carnitine (ALC) is derived from carnitine and is described as having several properties which may be beneficial in dementia. These include activity at cholinergic neurons, membrane stabilization and enhancing mitochondrial function. Work on the effects of ALC has been ongoing since the 1980s yet the mechanism of efficacy of ALC in cognitive decline remains unclear. Early studies suggested a beneficial effect of ALC on cognition and behaviour in aging subjects. However, later, larger studies have not supported these findings. Some of the difficulties lie in the differences in methodology and assessment tools used in the early and later studies. They are therefore difficult to compare. ALC is not currently in routine clinical use.Objectives
To establish whether Acetyl-l-carnitine is clinically effective in the treatment of people with dementia.Search strategy
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, EMBASE, MEDLINE, CINAHL, PsycINFO and LILACS on 8 November using the terms acetyl-l-carnitine, l-carnitine acetyl ester, acetylcarnitine, ALC. The search in November 2007 revealed no new studies.Selection criteria
All double-blind, randomized, trials involving people with dementia in which treatment with ALC was compared with a placebo groupData collection and analysis
Data were extracted by a reviewer (SH) and entered into RevMan 4.2 software. Where possible intention-to-treat data were used, but most of the analyses were of completers (people who completed the study).Main results
There are sixteen included trials, all of which included participants with mild-moderate dementia or cognitive decline. All trials assessed the cognitive effects of ALC and in addition most considered severity of dementia, functional ability and clinical global impression.
When considering clinical global impression (CGI-I) as a dichotomous variable (numbers improved versus numbers unchanged or worse) there were statistically significant treatment effects in favour of ALC at 12 and 24 weeks, (Peto odds ratio (OR) 1.90, 95% Confidence Interval (CI) 1.31 to 2.76) and (OR 2.33, 95% CI 1.31 to 4.14) but not at 52 weeks (OR 0.91, 95% CI 0.58 to 1.43). There was also a statistically significant treatment effect on MMSE at 24 weeks (Weighted Mean Difference (WMD) 0.69, 95% CI 0.09 to 1.29, P = 0.02), but not at 12 or 52 weeks. There was no evidence of benefit of ALC in the areas of severity of dementia, functional ability or Clinical Global Impression as a continuous measure.
Various adverse events were reported, but from the meta-analyses there were no statistically significant differences between treated and placebo groups.
There is evidence for benefit of ALC on clinical global impression as a categorical measure and on MMSE at 24 weeks, but there is no evidence using objective assessments in any other area of outcome. Given the large number of comparisons made, the statistically significant results may be due to chance. At present there is no evidence to recommend its routine use in clinical practice. Many of the trials used rather vague descriptions of dementia and trials using more strictly defined groups may be informative. Individual patient data may add to the findings, as would trials including other outcomes (e.g. mood and caregiver quality of life). However, the evidence does not suggest that ALC is likely to prove an important therapeutic agent. More work on the pharmacokinetics of ALC in humans is also required.
Hudson Sheila A, Tabet Naji
No evidence of benefit of Acetyl-l-carnitine for dementia
Acetyl-l-carnitine (ALC) is derived from carnitine and is described as having several properties which may be beneficial in dementia. Early studies suggested a beneficial effect of ALC on cognition and behaviour in aging subjects. However, later, larger studies have not supported these findings. The early and later studies differ widely in methodology and assessment tools used, and are therefore difficult to compare. There is no evidence of benefit of ALC in the areas of cognition, severity of dementia, functional ability or Clinical Global Impression as a continuous measure. An apparent beneficial effect on Clinical Global Impression assessed as a dichotomous variable may be due to chance. There was also a significant treatment effect on the Mini Mental State Examination (MMSE) at 24 weeks, but this result must be interpreted with caution in the context of significant heterogeneity in these trials. ALC is not currently in routine clinical use.
Implications for practice
The evidence of benefit of ALC for people with Alzheimer's disease does not justify recommending its routine clinical use.
Implications for research
Although this review intended to assess all dementia groups, all included studies focused on Alzheimer's disease. Only one small, excluded, unpublished study examined vascular dementia but reported negative findings (Andrea Stracciari 2001 personal communication) so there may be scope for further trials in other types of dementia.
As discussed, there is a lack of data relating to ALC pharmacokinetics in humans and more research in this area is desirable. The criteria used for dose selection should be derived from a thorough oral bioavailability study that would guarantee a consistent increase in ALC plasma levels in all patients.
Most studies also concentrated on outcomes in the areas of cognition, severity of dementia and ability to perform activities of daily living. Further studies including other relevant outcomes such as mood and caregiver quality of life would be valuable in dementia. However, the evidence so far available does not suggest that ALC is likely to prove an important therapeutic agent for the treatment of people with dementia.Get full text at The Cochrane Library
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