P4-344: Oral curcumin for the treatment of mild-to-moderate Alzheimer's disease: Tolerability and clinical and biomarker efficacy results of a placebo-controlled 24-week study

Abstract

Background: Curcumin is phenolic compound with anti-inflammatory and antioxidant properties that has been shown to have anti-amyloid activity in transgenic mice. The purpose of this study was to obtain tolerability and preliminary efficacy data of 2 gm/day and 4 gm/day of Curcumin C3 Complex in mild-to-moderate AD patients in a 24-week, randomized, double-blind study. Methods: Thirty-six patients were randomized to receive placebo, 2 gm, or 4 gm per day of curcumin in two divided doses. The MMSE, ADAS-Cog, NPI, and ADCS-ADL scales were performed at baseline and at 24 weeks’ time. Plasma and cerebrospinal fluid (CSF) samples were obtained at baseline and 24 weeks and Abeta40, Abeta42 measured in plasma and CSF and total tau and p-tau181 measured in CSF. Baseline and 24-week values were compared between groups using repeated measures ANOVA. Adverse events were recorded and the frequency of any adverse event at each visit compared between groups by chi-square. Results: Subjects’ age (mean 74 years), gender (62% female), baseline MMSE (mean 22.6), ADAS-Cog, NPI, and ADCS-ADL scores did not differ between treatment groups. 11 subjects on placebo, 9 on 2 grams and 10 on 4 grams of curcumin completed the study. In completer analyses, there were no differences or favorable trends between placebo and treatment groups on clinical measures. No difference in plasma or CSF biomarkers were found between groups except for a tendency (p 0.14) towards a lesser degree of increase in plasma Abeta42 in the combined group on 2 and 4 gm/day of curcumin. There were no differences between placebo and all treated patients’ change in laboratory values nor in the frequency of adverse events at any treatment visit. Conclusions: Orally administered Curcumin C3 Complex is safe in elderly persons treated for 24 weeks at doses up to 4 gm/day. Our data do not provide evidence for a large effect of curcumin on clinical and biochemical measures in mild-tomoderate AD patients at doses up to 4 gm/day. Limitations of this study include the small sample, short duration of treatment, and uncertain bioavailability of this curcumin formulation. Further analyses of clinical, pharmacokinetic, and biomarker data are pending.