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

Abstract

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.

Redox State in Professional Cyclists Following Competitive Sports Activity

“…This was the case of athletes treated with large doses of both Vitamin E and Vitamin C during high-intensity endurance exercise training where it was clearly shown that MDA and carbonylated proteins were increased. This fact witnesses that a pro-oxidant effect was achieved instead of reducing the oxidative burden [11] This suggests using a combination of physiological modulators [22] in low doses, since there are specific modulators that protect cell membranes, increase cytosol antioxidant capacity, support the production of antioxidant enzymes, and improve circulating antioxidant capacity [15] and the efficiency of erythrocytes [23].…”

β-Alanyl-L-Histidine Rescues Cognitive Deficits Caused by Feeding a High Fat Diet in a Transgenic Mouse Model of Alzheimer's Disease

“…The accumulation of peroxidized lipids would also impart a certain level of neurological deficits on the offspring of female mice fed with an HFD, implying that the oxidative stress caused by this diet is widespread throughout the body [8]. A recent pivotal study [9] has shown that treatment with antioxidants concomitantly with the administration of donepezil, an acetylcholinesterase inhibitor commonly prescribed for the treatment of early-stage AD, yields a significant improvement in the cognitive function of patients when compared to those treated only with donepezil. The results of this study, taken together with other studies on oxidative stress, have given rise to the hypothesis that treatment with antioxidants is beneficial in the treatment of early-onset AD.…”

Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders

“…In a double-blind placebo-controlled study addressing the therapeutic potential of carnosine in AD, it was assessed the efficacy of a combination of carnosine plus other antioxidants (formula F) in volunteers receiving donepezil (n = 26), in comparison to patients receiving donepezil plus placebo (n = 26) [90]. Using the Mini-Mental State Examination II (MMSE II) score, Cornelli [90] observed a significantly improvement of cognition in the group receiving donepezil plus formula F, as compared to those receiving donepezil plus placebo.…”

“…Using the Mini-Mental State Examination II (MMSE II) score, Cornelli [90] observed a significantly improvement of cognition in the group receiving donepezil plus formula F, as compared to those receiving donepezil plus placebo.…”