Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease
Introduction
Mild cognitive impairment (MCI) can be defined as an isolated deficit in recent memory [32] and it is frequently associated with decline to Alzheimer’s disease (AD) [27]. This type of cognitive decline is commonly observed in a large number of elderly patients, and other definitions of this tail end of the normal cognitive range have included terms such as aging-associated cognitive decline [18], or age-related cognitive decline [1].
A critical step in establishing a specific therapy in the earliest stage of a dementing disorder is the identification of subjects at risk. Therefore, neuroimaging, neuropsychological and biological methods are applied in this field with the purpose of determining the mechanisms by which MCI develops to AD, suggesting a common pathogenesis between these two clinical syndromes.
Many studies support the hypothesis that impaired energy metabolism and oxidative stress play an important role in the pathogenesis of AD [9]. Impaired mitochondrial function in AD may lead to an increased free radical-related damage affecting critical cellular key components [37], [39]. Cerebral tissue appears to be particularly vulnerable to free radical damage because of its low content of antioxidants, high content of polyunsaturated fatty acids of neuronal membranes and high oxygen requirements for its metabolism [9].
An increase in DNA, lipid and protein oxidation products has been found in blood and in post-mortem brain samples obtained from AD patients in comparison with controls [19]. The β-amyloid protein itself has been suggested as causing oxidative damage to neurons [7], [20]. Particularly high levels of isoprostanes, a marker of lipid peroxidation, were found in brain, plasma and urine of a transgenic mouse model of AD amyloidosis, showing a clear relationship between central and peripheral markers of oxidative stress [35].
A three-fold increase in 8-hydroxy-2-deoxyguanosine (8-oxo-dG) was found in mtDNA isolated from cortical tissue of AD patients in comparison to nuclear DNA (nDNA) [22]. An increased 8-oxo-dG lymphocyte DNA content has also been found in AD donors as compared to control subjects [24]. Interestingly, this increase has been found to be inversely correlated to plasma levels of several carotenoids, which are hydrophobic antioxidant micronutrients, in AD patients [23].
The measurement of peripheral antioxidants is considered an appropriate way of looking at oxidative stress in various disease states in humans [33]. Also in light of the scarce data regarding the role of oxidative stress and antioxidants in MCI, the present study was conducted to evaluate peripheral levels and activities of a broad spectrum of non-enzymatic and enzymatic antioxidants in elderly subjects with MCI. In this context, levels and activities of antioxidants were evaluated in normal elderly subjects and patients with AD for comparison.
Section snippets
Subjects
Twenty-five free-living subjects with MCI (11 males, 14 females; mean age 75.8±4.8 years) defined as a subjective complaint of defective memory, normal activities of daily living, normal general cognitive functioning, abnormal memory for age as demonstrated by a performance of at least 1.5 S.D. below the age norm, absence of dementia and a Clinical Dementia Rating (CDR) scale of 0.5 [31] and 63 free-living subjects with AD (17 males, 46 females; mean age 76.8±6.9 years) according to
Results
Demographic and clinical characteristics of the population studied are presented in Table 1. There was no significant difference between groups regarding age, years of education, BMI and MNA scores. Biochemical indexes of nutritional status and dietary intake did not differ among groups (data not shown). Table 1 also shows apolipoprotein E (ε4) allele distribution.
MCI and AD patients showed lower mean levels of non-enzymatic antioxidants and lower activities of antioxidant enzymes as compared
Discussion
A large body of evidence shows that the risk of MCI patients to develop AD increases every year after the diagnosis [31]. Thus, it is fundamental to understand whether MCI is a prodromal stage of AD, and whether a common pathogenesis among the two forms does exist.
In this study, the modification of several components of the antioxidant defense system of the organism in relation to the presence of MCI is shown. Our main finding is that plasma antioxidants are similarly depleted in MCI and AD.
Acknowledgements
This research was supported by a grant from the University of Perugia to P.M. M.C.P. is an EU Marie-Curie Fellow for the programme “Quality of Life and Management of Living Resources”, project entitled “Nutritional health-sustaining factors and determinants of healthy aging: oxidative stress-related biomarkers of successful aging and age-related diseases”.
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