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Treatment of Alzheimer’s Disease with a Cholinesterase Inhibitor Combined with Antioxidants

Cornelli U.
Loyola University Chicago School of Medicine, Maywood, Ill., USA Neurodegenerative Dis 2010;7:193–202 (DOI:10.1159/000295663)


A formula (formula F) was prepared to counteract oxidative stress (OS) in the brain. The formula contained the most common antioxidants and was intended to: (a) protect proteins, lipids, DNA and proteoglycans from oxidation (carnosine, coenzyme Q10, vitamin E, vitamin C, β-carotene, selenium, L-cysteine and ginkgo biloba); (b) reduce homocysteine (HCy) blood levels (vitamins B6, B9 and B12), and (c) sustain the pentose phosphate cycle in circulating cells (vitamins B1, B2 and B3). Formula F contained low doses of each antioxidant component and was administered in a two-phase ampoule. A cohort of 52 patients (21 males and 31 females) affected with moderate probable AD (according to NINCDS-ARDA and NINCS-AIREN criteria) already being treated with donepezil (5 mg/day for at least two months) was randomly divided into two groups, and followed for 6 months. A double-blind design was used in which 26 cases were treated once a day with formula F plus donepezil, and the other 26 with placebo plus donepezil. The level of OS was measured on the basis of a d-ROMs test (which measures plasma hydroperoxides), plasma HCy and glutathione, and percentage of sickle erythrocytes. The two patient groups were comparable for all variables (age, sex, concomitant diseases, ApoE ε4, MMSE II score, OS, antioxidant reserve and sickle erythrocytes). Forty-eight subjects completed the trial. Significant decreases in OS and HCy were only observed when there was an increase in glutathione (in erythrocytes) and a decrease in sickle erythrocytes in patients treated with formula F. The MMSE II score remained almost the same in the group treated with donepezil and placebo, whereas some significant improvements were found in the group treated with donepezil plus formula F.


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