By Chris Berrie
PRAGUE, Czech Republic -- March 17, 2009 -- Addition of a defined antioxidants formulation (Formula F) to donepezil treatment of patients with mild Alzheimer's disease (AD) substantially reduces oxidative stress and provides significant benefits over treatment with donepezil alone, according to results of a randomised, controlled study.
Principal investigator Umberto Cornelli, MD, PhD, Cornelli Foundation and Loyola University Chicago School of Medicine, Maywood, Illinois, presented the results on March 14 here at the 9th International Conference on Alzheimer's and Parkinson's Diseases (ADPD).
As Dr. Cornelli indicated, oxidative stress in the brain arises due to various determining factors, including brain and blood-brain barrier vasculature, mitochondrial activity, homocysteine and proteoglycan levels, and beta-amyloid and erythrocyte function.
Dietary and supplemental antioxidants have been implicated in reduced risk of AD, and the defined antioxidant formulation Formula F has been shown to be active in reducing oxidative stress in the short-term. The present study was thus designed to determine the antioxidant and potentially beneficial effects of Formula F in patients with mild AD.
The study enrolled patients aged 65 to 85 years with mild disease, defined as a Mini-Mental State Examination (MMSE)-II score of 21 to 26, while receiving donepezil 5 mg/day for at least 3 months. Patients were permitted to receive concomitant therapies at stable doses for at least 3 months to require daily assistance for treatment and food preparation.
Following randomisation, 25 patients were randomised to treatment with donepezil 5 mg/day plus placebo (placebo group) and 23 patients to treatment with donepezil 5 mg/day plus Formula F at a dose of 1 ampoule daily (Formula F group). Treatment duration was 6 months.
According to the researchers, plasma hydroperoxide levels were used as a marker of oxidative stress and were measured using the determination of reactive oxygen metabolites (d-ROMS) test.
Patients' mean ages in the 2 treatment arms were 74 and 75 years, respectively, and men made up 40% and 39% of the 2 groups, respectively.
Baseline clinical characteristics across the placebo and Formula F groups were similar for the main assessments of MMSE-II score, d-ROMS test, homocysteine levels, glutathione levels, and elongated erythrocytes.
The primary outcome measure was the change in the d-ROMS plasma test at 6 months of treatment and saw little change in the placebo group but a significant reduction from both baseline (P < .05) and over placebo (P < .05) for the Formula F group.
Similarly, significant reductions (P < .05) were seen for Formula F over placebo for the secondary outcome laboratory assessment measures of plasma homocysteine (P < .05) and percentage elongated erythrocytes (P < .05). Both these and the erythrocyte glutathione measures also showed significant reductions only with the Formula F group for the baseline to 6-month reductions (P < .05 for all).
While the MMSE-II assessments saw benefits to both the control (+0.3) and Formula F (+1.1) treatment groups, these were not substantial. However, when analysed according to patients showing improvements, there was a significant benefit of Formula F addition to donepezil treatment (placebo, 4; Formula F, 12; P < .05).
Dr. Cornelli noted some interesting aspects of the correlations between MMSE-II and d-ROMS with erythrocyte glutathione (r = .881, .499, respectively) and elongation (r = .816, .489, respectively), which indicated that delaying of the MMSE-II deterioration seems to be related to the erythrocyte function recovery.
[Presentation title: Treatment of Alzheimer's Disease With Cholinesterase Inhibition Combined With Antioxidants. Abstract 1]
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