A 1-year controlled trial of acetyl-L-carnitine in early-onset AD

Objective: To determine the efficacy of acetyl-L-carnitine (ALCAR) on the r ate of decline in early-onset AD patients. Methods: A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were 45 to 65 years old, with a diagnosis of probable AD according to Natio nal Institute of Neurological Communicative Disorders-Alzheimer's Disease a nd Related Disorders Association criteria and had a Mini-Mental State Exami nation (MMSE) score between 12 and 26. They were treated with ALCAR (1 g ti d) or placebo. Primary outcome measures were the Alzheimer's Disease Assess ment Scale-Cognitive Component and the Clinical Dementia Rating Scale. Seco ndary measures included the ADAS Non-Cognitive Subscale, the MMSE, an Activ ities of Daily Living Scale (ADL), and a Clinician-Based Impression of Chan ge (CIBIC). Results: Two-hundred twenty-nine patients were enrolled and ran domized to drug treatment, with 117 taking placebo and 112 taking ALCAR. Th ere were no significant differences between the two groups at baseline. For the primary outcome measures, there were no significant differences betwee n the treatment groups on the change from baseline to endpoint in the inten t-to-treat analysis. In the completer sample only, there was less deteriora tion in the MMSE for the ALCAR-treated subjects. There was no difference in rate of decline on the CIBIC and the ADL scale. There were no significant differences in the incidence of adverse events by treatment arm. Conclusion : Overall, in a prospectively performed study in young-onset AD patients, A LCAR failed to slow decline. Less decline was seen on the MMSE in the compl eter sample only, with the difference being mediated by reducing decline in attention. A combination of ALCAR and a cholinesterase inhibitor should be tested for additivity.