Abstract
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. 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. 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. 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. Both indices were more associated with vascular involvement and the severity of brain atrophy or ischemia rather than with degree of cognitive decline.
Highlights
Progressive degeneration of neurons, a hallmark of neurodegenerative disorders, leads to serious deficits in cognitive performance and general functioning.[1]
We demonstrated an increase in MDA/ TBARS accompanied by a drop in Paraoxonase 1 (PON1) activity in patients with dementia, these with vascular involvement, which was related to the severity of brain atrophy or ischemia rather than to the degree of cognitive decline
Some authors have reported the lack of a significant difference in MDA between controls and MCI patients[37] or its gradual increase along the sequence from healthy individuals to MCI and Alzheimer’s disease (AD),[32] we and others found serum MDA/TBARS to accumulate in MCI and AD patients to a similar extent,[33] substantiating the notion that lipid peroxidation is a phenomenon that occurs early in the progression of dementia.[34]
Summary
Progressive degeneration of neurons, a hallmark of neurodegenerative disorders, leads to serious deficits in cognitive performance and general functioning.[1]. Alzheimer’s disease (AD) is the main cause of dementia in the elderly population, followed by vascular dementia (VaD). Alzheimer’s disease is estimated to account for 60–80% of cases and is characterized by the accumulation of extracellular β-amyloid plaques and intracellular neurofibrillary tangles.[1] Vascular dementia is the result of the blockage or damage of the cerebral blood vessels, leading to infarcts, bleeding and/or ischemia and to brain injury. It was initially considered to be the sole form of dementia attributable to vascular lesions; several studies have demonstrated that the development of cardiovascular risk factors play a substantial role in AD. The co-existence of AD and VaD pathologies is observed in the vast majority of mixed dementia (MD) cases.[1]. Impaired antioxidative capacity and enhanced lipid peroxidation (reflected by malondialdehyde rise) accompany dementias
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