Vitamin E and donepezil for the treatment of mild cognitive impairment.
ABSTRACT Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease.
In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function.
A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers.
Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo.
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ABSTRACT: Vitamin E is an important antioxidant that primarily protects cells from damage associated with oxidative stress caused by free radicals. The brain is highly susceptible to oxidative stress, which increases during ageing and is considered a major contributor to neurodegeneration. High plasma vitamin E levels were repeatedly associated with better cognitive performance. Due to its antioxidant properties, the ability of vitamin E to prevent or delay cognitive decline has been tested in clinical trials in both ageing population and Alzheimer's disease (AD) patients. The difficulty in performing precise and uniform human studies is mostly responsible for the inconsistent outcomes reported in the literature. Therefore, the benefit of vitamin E as a treatment for neurodegenerative disorders is still under debate. In this review, we focus on those studies that mostly have contributed to clarifying the exclusive function of vitamin E in relation to brain ageing and AD.Nutrients 12/2014; 6(12):5453-5472. · 3.15 Impact Factor
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ABSTRACT: It is estimated that >90% of Americans do not consume sufficient dietary vitamin E, as α-tocopherol, to meet estimated average requirements. What are the adverse consequences of inadequate dietary α-tocopherol intakes? This review discusses health aspects where inadequate vitamin E status is detrimental and additional vitamin E has reversed the symptoms. In general, plasma α-tocopherol concentrations <12 μmol/L are associated with increased infection, anemia, stunting of growth, and poor outcomes during pregnancy for both the infant and the mother. When low dietary amounts of α-tocopherol are consumed, tissue α-tocopherol needs exceed amounts available, leading to increased damage to target tissues. Seemingly, adequacy of human vitamin E status cannot be assessed from circulating α-tocopherol concentrations, but inadequacy can be determined from “low” values. Circulating α-tocopherol concentrations are very difficult to interpret because, as a person ages, plasma lipid concentrations also increase and these elevations in lipids increase the plasma carriers for α-tocopherol, leading to higher circulating α-tocopherol concentrations. However, abnormal lipoprotein metabolism does not necessarily increase α-tocopherol delivery to tissues. Additional biomarkers of inadequate vitamin E status are needed. Urinary excretion of the vitamin E metabolite α-carboxy-ethyl-hydroxychromanol may fulfill this biomarker role, but it has not been widely studied with regard to vitamin E status in humans or with regard to health benefits. This review evaluated the information available on the adverse consequences of inadequate α-tocopherol status and provides suggestions for avenues for research.Advances in Nutrition 09/2014; 5(5):503-14. · 3.20 Impact Factor
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ABSTRACT: Mild cognitive impairment and mild dementia are common problems in the elderly. Primary care physicians are the first point of contact for most patients with these disorders and should be familiar with their diagnosis, prognosis, and management. Both mild cognitive impairment and mild dementia are characterized by objective evidence of cognitive impairment. The main distinctions between mild cognitive impairment and mild dementia are that in the latter, more than one cognitive domain is invariably involved and substantial interference with daily life is evident. The diagnosis of mild cognitive impairment and mild dementia is based mainly on the history and cognitive examination. The prognosis for mild cognitive impairment and mild dementia is an important motivation for diagnosis because in both, there is a heightened risk for further cognitive decline. The etiology of mild cognitive impairment and mild dementia can often be established through the clinical examination, although imaging and other laboratory tests may also contribute. Although Alzheimer disease is the most common cause of both, cerebrovascular disease and Lewy body disease make important contributions. Pharmacological treatments are of modest value in mild dementia due to Alzheimer disease, and there are no approved pharmacological treatments for mild cognitive impairment of any etiology. Nonetheless, new-onset cognitive impairment is a worrisome symptom to patients and families that demands answers and advice. If a patient is having difficulties managing medications, finances, or transportation independently, diagnosis and intervention are necessary to ensure the health and safety of the patient.Mayo Clinic Proceedings 10/2014; 89(10):1452-1459. · 5.81 Impact Factor