PON-1 and ferroxidase activities in older patients with mild cognitive impairment, late onset Alzheimer's disease or vascular dementia

Background: A large body of evidence suggests that not only cerebral but also systemic oxidative stress (OxS) might be involved in the pathogenesis of late onset Alzheimer's disease (LOAD) and vascular dementia (VAD), as well as of the prodromal phase of dementia, the so-called mild cognitive impairment (MCI). In the present study, we evaluated whether paraoxonase 1 (PON-1) and ferroxidase (FeOx) activities, because of their well acknowledged effectiveness as systemic antioxidants, might be associated with dementia and/or MCI. Methods: Serum arylesterase and paraoxonase of PON-1, along with FeOx I (ceruloplasmin-related) and II activities were assessed in 223 MCI, 162 LOAD, 65 VAD patients, and in 143 older normal cognitive controls. Results: Among the enzymatic activities examined, only arylesterase significantly changed across the groups (ANOVA: p<0.001), with similar lower levels in MCI, LOAD, and VAD compared to controls. By multivariate logistic regression analysis we showed that, in respect to controls, low levels (under the median value) of serum arylesterase were independently associated with an increase in the likelihood of being affected by LOAD [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.5-5.0], VAD (OR 2.7, 95% CI 1.2-6.2), or MCI (OR 2.3, 95% CI 1.3-3.8). Conclusions: Overall, our results suggest that depression of PON-1, and in particular, of arylesterase activity, in serum might be an early feature of dementia-related diseases. Further longitudinal exploration of the role of this enzyme in the onset and progression of these disorders are required.