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

Cervellati, Carlo; Trentini, Alessandro; Romani, Arianna; Bellini, Tiziana; Bosi, Cristina; Ortolani, Beatrice; Zurlo, Amedeo; Passaro, Angelina; Seripa, Davide; Zuliani, Giovanni

doi:10.1111/jnc.13240

Cited by 46 publications

(42 citation statements)

References 43 publications

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“…Therefore, a total of 46 papers were eventually included in this study ( Figure 1) and the main findings are summarized in Table 1. More in details, 8 studies deal with serum biomarkers [9][10][11][12][13][14][15][16], 10 with cerebrospinal fluid (CSF) [17][18][19][20][21][22][23][24][25][26], 4 with neuroimaging [27][28][29][30], 6 with histopathology [31][32][33][34][35][36], and 14 with transcranial magnetic stimulation (TMS) [37][38][39][40][41][42][43][44][45][46][47][48][49][50]; 4 studies included more than one technique: one studied both serum and CSF markers [51], two both serum and neuroimaging [52,53], and one both CSF and neuroimaging…”

Section: Resultsmentioning

confidence: 99%

“…For instance, pro-inflammatory metabolites (such as NO-related molecules), cytokines (including IL-1β, TNF-α, IFN-γ, IL-4, IL-5, IL-8, G-CSF, and MIP-1b), and markers of endothelial dysfunction (e.g., homocysteine) were found to be increased in VaD patients [11,16,[51][52][53]. Furthermore, an altered systemic redox balance was demonstrated in VCI, in which reduced antioxidant enzymes, such as the activity of arylesterase and paraoxonase, were associated with the risk of developing dementia [13,14]. In addition, the concentrations of some CSF proteins can also help to distinguish among different forms of dementia.…”

Section: Summary Of Findingsmentioning

confidence: 93%

“…The anti-inflammatory and antioxidant functions of high-density lipoprotein, assessed through the dosage of the catalyzing enzyme, showed that low serum arylesterase levels were significantly associated with a higher probability of VaD [14]. Significant low arylesterase and paraoxonase activities were also observed in patients with mild cognitive impairment (MCI) who developed VaD, also predicting the risk of conversion after two years [13]. Additionally, simultaneously high levels of homocysteine and uric acid were associated with higher probability to develop VaD [9].…”

Section: Serummentioning

confidence: 99%

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Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

Vinciguerra

Lanza

Puglisi

et al. 2020

IJMS

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In the last years, there has been a significant growth in the literature exploring the pathophysiology of vascular cognitive impairment (VCI). As an "umbrella term" encompassing any degree of vascular-related cognitive decline, VCI is deemed to be the most common cognitive disorder in the elderly, with a significant impact on social and healthcare expenses. Interestingly, some of the molecular, biochemical, and electrophysiological abnormalities detected in VCI seem to correlate with disease process and progression, eventually promoting an adaptive plasticity in some patients and a maladaptive, dysfunctional response in others. However, the exact relationships between vascular lesion, cognition, and neuroplasticity are not completely understood. Recent findings point out also the possibility to identify a panel of markers able to predict cognitive deterioration in the so-called "brain at risk" for vascular or mixed dementia. This will be of pivotal importance when designing trials of disease-modifying drugs or non-pharmacological approaches, including non-invasive neuromodulatory techniques. Taken together, these advances could make VCI a potentially preventable cause of both vascular and degenerative dementia in late life. This review provides a timely update on the recent serological, cerebrospinal fluid, histopathological, imaging, and neurophysiological studies on this "cutting-edge" topic, including the limitations, future perspectives and translational implications in the diagnosis and management of VCI patients.

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Section: Resultsmentioning

confidence: 99%

Section: Summary Of Findingsmentioning

confidence: 93%

Section: Serummentioning

confidence: 99%

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Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

Vinciguerra

Lanza

Puglisi

et al. 2020

IJMS

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“…Others, like us, have found it to be lowered in dementias with vascular involvement. 26,27,29 Moreover, Cervellati et al 30 reported low PON1 activity to be associated with an increased risk of MCI progression to VaD rather than AD. Even though the difference in PON1 activity between patients with dementia with and without vascular involvement in our cohort did not reach statistical significance, the enzyme association with vascular involvement seems to be confirmed by the negative correlation between PON1 activity and HIS index, reflecting the degree of ischemia.…”

Section: Discussionmentioning

confidence: 99%

Paraoxonase 1 decline and lipid peroxidation rise reflect a degree of brain atrophy and vascular impairment in dementia

Bednarz−Misa¹,

Berdowska²,

Zboch³

et al. 2020

Adv Clin Exp Med

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Bednarz-Misa I, Berdowska I, Zboch M, et al. Paraoxonase 1 decline and lipid peroxidation rise reflect a degree of brain atrophy and vascular impairment in dementia. AbstractBackground. Paraoxonase 1 (PON1) is an enzyme with the capability to protect against lipid oxidation and atherosclerotic lesions formation. Impaired antioxidative capacity and enhanced lipid peroxidation (reflected by malondialdehyde rise) accompany dementias.Objectives. The aim of this study was to discern the possible differences in the activity and phenotype distribution of PON1, and lipid peroxidation level in dementias of neurodegenerative and vascular pathology, to assess whether they reflect structural changes in the brain, and to evaluate their potential as dementia markers.Material and methods. Paraoxonase 1 arylesterase activity and polymorphisms (dual-substrate method), and malondialdehyde/thiobarbituric acid reactive substances (MDA/TBARS) levels were determined spectrophotometrically in 257 serum samples derived from 136 dementive patients (with Alzheimer's disease (AD; n = 63), vascular dementia (VaD; n = 40) and mixed-type dementia (MD; n = 33), as well as from 121 non-dementive individuals. The results were analyzed with reference to dementia type and severity (assessed with Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scales), structural brain changes (estimated with magnetic resonance imaging (MRI) -Global Cortical Atrophy (GCA), Medial Temporal lobe Atrophy (MTA) and Fazekas scales)) and brain ischemia (Hachinski Ischemic Scale (HIS) index), and evaluated using receiver operating characteristic (ROC) analysis.Results. Malondialdehyde/thiobarbituric acid reactive substances were increased in dementia (more in VaD than AD). In patients with vascular involvement, MDA/TBARS elevation reflected a degree of global cortical atrophy. Paraoxonase 1 activity was decreased in patients with dementia, especially in patients with severe cognitive deficits. In VaD, a drop in PON1 reflected a degree of MTA and brain ischemia. MDA/TBARS displayed 75% accuracy as a general dementia marker, but, similarly to PON1, were a poor differential marker.Conclusions. Both indices were more associated with vascular involvement and the severity of brain atrophy or ischemia rather than with degree of cognitive decline.

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“…PON1 activity varies widely among individuals, up to 40-fold (10,11) , and it is influenced by genetic, developmental, environmental and pathologic determinants (1,(12)(13)(14) . Low PON1 and AE activities have been associated with a variety of health outcomes (15)(16)(17) . For instance, low PON1 activity has been suggested as a predictor for coronary events (15) , and both low PON1 and AE activities have been associated with an increased risk of vascular dementia (16) .…”

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confidence: 99%

Association between alcohol consumption and serum paraoxonase and arylesterase activities: a cross-sectional study within the Bavarian population

et al. 2016

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High alcohol consumption is an important risk factor for chronic disease and liver degeneration. Paraoxonase (PON1) and arylesterase (AE) are functions of the enzyme paraoxonase, which is synthesised by the liver. Paraoxonase circulates in plasma bound to HDL and hydrolyses lipid peroxides, protecting lipoproteins against oxidative modification. It has been shown that excessive alcohol consumption leads to a reduction of serum PON1 and AE activities; however, studies investigating the association with low and moderate alcohol consumption are scarce. We investigated the cross-sectional association between alcohol consumption and serum activities of PON1 and AE using data from the population-based Bavarian Food Consumption Survey II survey. PON1 and AE activities were quantified in serum samples of 566 male and female study participants (aged 18-80 years), and dietary intake including alcohol consumption was estimated from three 24-h dietary recalls. The association between alcohol consumption and PON1 and AE activities was analysed using linear regression, adjusted for age, sex and socio-economic status. There was no strong association between alcohol consumption and enzymatic activities of PON1 and AE in the Bavarian population. PON1 activity was seen to be lowest in non-drinkers (0 g/d) and highest in people who consumed 15·1-30 g of alcohol/d. AE activity increased across alcohol consumption categories, with a mean maximum difference of 14 U/ml (P for linear trend 0·04). These associations were attenuated after adjustment for blood concentrations of HDL. The results of this study do not support the hypothesis that alcohol consumption is related to important alterations in PON1 and AE activities.

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

Cited by 46 publications

References 43 publications

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

Paraoxonase 1 decline and lipid peroxidation rise reflect a degree of brain atrophy and vascular impairment in dementia

Association between alcohol consumption and serum paraoxonase and arylesterase activities: a cross-sectional study within the Bavarian population

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