Growing evidence from in vitro and animal model experiments suggest a role of oxidative stress (OxS) in the pathogenesis of late Alzheimer’s disease (LOAD) and vascular dementia (VAD). However, the definitive appreciation of the involvement of OxS in these two most common forms of dementia-related diseases need a confirmation in a population-based study on a large sample. The aim of our study was to investigate the possible relationship between OxS and the onset and clinical progression of LOAD and VAD. To achieve this purpose a sample of 431 older individuals: 101 LOAD, 43 VAD, 188 mild cognitive impairment (MCI, pre-dementia condition) and 99 healthy controls were enrolled and assessed for serum levels of hydroperoxides (HY; i.e., by products of lipid peroxidation), total amount of non-enzymatic antioxidants (RAP), uric acid (UA), thiols (TH) and advanced oxidation protein products (AOPP). In addition, a subgroup (n=126) of MCI patients were followed-up for averagely 2 years to evaluate if baseline levels of OxS markers were either related or not to the conversion to LOAD or VAD. Multivariate analysis (covariates: age, gender, smoking and comorbidities) of our cross-sectional data showed a significant (p<0.01 for all) decrease of RAP levels compared to controls in MCI (-24.5%), LOAD (-24.2%) and VAD (-29%) patients. On the other hand, HY emerged as significantly higher (p<0.05) in LOAD patients (+30.6 %), (but not in MCI and VAD) with respect to healthy. Multivariate logistic regression highlighted the presence of a similar unfavourable oxidative balance (high HY and low RAP) in MCI (O.R.: 4.87; 95%CI: 1.02-23.55) and LOAD (O.R.: 6.99; 95%CI, 1.87-25.21). Noteworthy, no differences were found in OxS markers between MCI patients who converted to LOAD (n=29) or to VAD (n=15) and those that remained stable (n=82) after follow-up time. Overall, our results suggest that systemic redox imbalance might be a significant feature of early stage of dementia. Moreover, the similar (deranged) oxidative profile in MCI and LOAD, could account for the observed inability of OxS markers to predict the conversion from prodromal phase to dementia.

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Systemic oxidative stress might be in the path from normal cognitive function to dementia: data from cross-sectional and longitudinal study.

ROMANI, Arianna;CREMONINI, Eleonora;CERVELLATI, Carlo;BOSI, Cristina;MAGON, Stefania;SQUERZANTI, Monica;BERGAMINI, Carlo;ZULIANI, Giovanni
2014

Abstract

Growing evidence from in vitro and animal model experiments suggest a role of oxidative stress (OxS) in the pathogenesis of late Alzheimer’s disease (LOAD) and vascular dementia (VAD). However, the definitive appreciation of the involvement of OxS in these two most common forms of dementia-related diseases need a confirmation in a population-based study on a large sample. The aim of our study was to investigate the possible relationship between OxS and the onset and clinical progression of LOAD and VAD. To achieve this purpose a sample of 431 older individuals: 101 LOAD, 43 VAD, 188 mild cognitive impairment (MCI, pre-dementia condition) and 99 healthy controls were enrolled and assessed for serum levels of hydroperoxides (HY; i.e., by products of lipid peroxidation), total amount of non-enzymatic antioxidants (RAP), uric acid (UA), thiols (TH) and advanced oxidation protein products (AOPP). In addition, a subgroup (n=126) of MCI patients were followed-up for averagely 2 years to evaluate if baseline levels of OxS markers were either related or not to the conversion to LOAD or VAD. Multivariate analysis (covariates: age, gender, smoking and comorbidities) of our cross-sectional data showed a significant (p<0.01 for all) decrease of RAP levels compared to controls in MCI (-24.5%), LOAD (-24.2%) and VAD (-29%) patients. On the other hand, HY emerged as significantly higher (p<0.05) in LOAD patients (+30.6 %), (but not in MCI and VAD) with respect to healthy. Multivariate logistic regression highlighted the presence of a similar unfavourable oxidative balance (high HY and low RAP) in MCI (O.R.: 4.87; 95%CI: 1.02-23.55) and LOAD (O.R.: 6.99; 95%CI, 1.87-25.21). Noteworthy, no differences were found in OxS markers between MCI patients who converted to LOAD (n=29) or to VAD (n=15) and those that remained stable (n=82) after follow-up time. Overall, our results suggest that systemic redox imbalance might be a significant feature of early stage of dementia. Moreover, the similar (deranged) oxidative profile in MCI and LOAD, could account for the observed inability of OxS markers to predict the conversion from prodromal phase to dementia.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/2278227
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