Growing in vitro and animal evidence suggests a crucial role of oxidative stress (OxS) in the neurodegenerative process occurring in late Alzheimer’s disease (LOAD) and Vascular Dementia (VAD). However, thus far, in vivo studies conducted onliving humans failed to definitely proved the implication of oxidative mechanisms in the onset and progression of these two major forms of dementia. In the attempt to address this issue we evaluated a pattern of multiple peripheral markers of OxS in large sample including 223 mild cognitive impairment (MCI), 162 LOAD, 65 VAD and 143 older normal cognitive controls. Methods:The sample subjects were evaluated for serum markers of biomolecular oxidative damage (lipid hydroperoxides and advanced oxidation protein products) along with enzymatic (arylesterase and paraoxonase activities of PON-1 and Ferroxidase I and II activities) and non-enzymatic [residual antioxidant power (RAP)], protein thiols and uric acid) antioxidants. Results: Multivariate analysis (covariates: age, gender, smoking and comorbidities) of our data showed a significant increase (p<0.05) of hydroperoxides in LOAD patients (+30.6 %), (but not in MCI and VAD) with respect to controls. Moreover, residual antioxidant power emerged as significantly lower in MCI (-24.5%), LOAD (-24.2%) and VAD (-29%) patients, compared to controls (p<0.01 for all). The trend towards a worse oxidative balance in demented patients was further confirmed by the results obtained with the assessment of arylesterase activity, which was independently associated with the likelihood of having MCI [odds ratio (OR): 2.3; 95% confidence intervals (CI): 1.3-3.8], LOAD (O.R.: 2.8; 95% CI: 1.5 – 5.0) or VAD (O.R.: 2.7; 95% CI: 1.3 – 3.8). Conclusions: Overall, our data indicate that a dysregulation of systemic antioxidant defences may play a role in the onset of dementia-related diseases. Indeed, a significant derangement in redox balance imbalance appears to be already present in the prodromal stage of dementia. If confirmed by other studies, our results might indirectly support the use of dietary antioxidants in order to rebalance the altered redox homeostasis in patients affected by MCI and LOAD.

P3-087: Late-onset Alzheimer disease and vascular dementia are precociously associated with a derangement in systemic oxidative balance

Romani, Arianna
Primo
;
Cremonini, Eleonora
Secondo
;
Cervellati, Carlo;Bosi, Cristina;Squerzanti, Monica;Bergamini, Carlo
Penultimo
;
Zuliani, Giovanni
Ultimo
2015

Abstract

Growing in vitro and animal evidence suggests a crucial role of oxidative stress (OxS) in the neurodegenerative process occurring in late Alzheimer’s disease (LOAD) and Vascular Dementia (VAD). However, thus far, in vivo studies conducted onliving humans failed to definitely proved the implication of oxidative mechanisms in the onset and progression of these two major forms of dementia. In the attempt to address this issue we evaluated a pattern of multiple peripheral markers of OxS in large sample including 223 mild cognitive impairment (MCI), 162 LOAD, 65 VAD and 143 older normal cognitive controls. Methods:The sample subjects were evaluated for serum markers of biomolecular oxidative damage (lipid hydroperoxides and advanced oxidation protein products) along with enzymatic (arylesterase and paraoxonase activities of PON-1 and Ferroxidase I and II activities) and non-enzymatic [residual antioxidant power (RAP)], protein thiols and uric acid) antioxidants. Results: Multivariate analysis (covariates: age, gender, smoking and comorbidities) of our data showed a significant increase (p<0.05) of hydroperoxides in LOAD patients (+30.6 %), (but not in MCI and VAD) with respect to controls. Moreover, residual antioxidant power emerged as significantly lower in MCI (-24.5%), LOAD (-24.2%) and VAD (-29%) patients, compared to controls (p<0.01 for all). The trend towards a worse oxidative balance in demented patients was further confirmed by the results obtained with the assessment of arylesterase activity, which was independently associated with the likelihood of having MCI [odds ratio (OR): 2.3; 95% confidence intervals (CI): 1.3-3.8], LOAD (O.R.: 2.8; 95% CI: 1.5 – 5.0) or VAD (O.R.: 2.7; 95% CI: 1.3 – 3.8). Conclusions: Overall, our data indicate that a dysregulation of systemic antioxidant defences may play a role in the onset of dementia-related diseases. Indeed, a significant derangement in redox balance imbalance appears to be already present in the prodromal stage of dementia. If confirmed by other studies, our results might indirectly support the use of dietary antioxidants in order to rebalance the altered redox homeostasis in patients affected by MCI and LOAD.
Oxidative stress, Alzheimer, Vascular Dementia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/2419106
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