Serum paraoxonase and arylesterase activities of paraoxonase‐1 ( PON ‐1), mild cognitive impairment, and 2‐year conversion to dementia: A pilot study

Converging lines of evidence suggest that paraoxonase‐1 (PON‐1) may confer protection against inflammatory and oxidative challenge which, in turn, plays a key‐role in the onset and progression of dementia. The aim of this study was to evaluate whether serum PON‐1 paraoxonase/arylesterase activities might predict the clinical conversion of mild cognitive impairment (MCI) to late‐onset Alzheimer's disease (LOAD) or vascular dementia (VAD). Serum paraoxonase and arylesterase activities were measured by spectrophotometric assays at baseline in 141 MCI patients (median age: 77 years; interquartile range 71–81) and in 78 healthy controls (median age: 76 years; interquartile range 73–79). After 2 years of follow‐up, 86 MCI remained stable (MCI/MCI), 34 converted to LOAD (MCI/LOAD), whereas 21 converted to VAD (MCI/VAD). Baseline arylesterase activity was lower in all MCI groups compared with controls (all p < 0.01), whereas paraoxonase activity was lower in MCI/VAD group compared to controls (p < 0.05) and MCI/MCI patients (p = 0.009). Low paraoxonase and arylesterase activities (I quartile) were associated to higher risk of conversion to VAD (OR: 3.74, 95% CI: 1.37–10.25 and OR: 3.16, 95% CI: 1.17–8.56, respectively). Our results suggest that in MCI patients low PON‐1 activity might contribute to identify individuals susceptible to develop vascular dementia. image Our study showed that in patients with mild cognitive impairment (MCI) low serum levels of paraoxonase‐1 (PON‐1) activity is associated with a higher likelihood of developing Vascular Dementia, but not Alzheimer's Disease. The observed connection might be explained by the ability of PON‐1 to retard low‐density lipoprotein (LDL) oxidation, decrease oxidative stress, attenuate inflammation, and increase cholesterol efflux.