Cognitive impairment and Alzheimer's disease: Links with oxidative stress and cholesterol metabolism

Abstract

Oxidative stress has be en implicated in the progression of a number of neurodegenerative diseases, inc1uding Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis. We carried out a~ in-depth study of cognitive impainnent and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP), plasma malondialdehyde and total antioxidative capacity (T AC), as well as cholesterol parameters, in two subsets ofsubjects, AD patients (n = 59) and a control group ofneurologically normal subjects (n = 29), attending thc University Hospital Salvador in Santiago, Chile. Cognitivc impairment was assessed by a sct of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitatíoll, Semantic Verbal Fluency of animals or words with initial A, Test ofMcmory Alteration, Frontal Asscssmcnt Battcry), whilc the levels ofthose oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol) of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC) ofpatients. In this context, the subset of subjects exhibiting cognitive impairment were divided into two subgroups according with their Global Dementia Scale performance: a subgroup with mild AD and a subgroup with moderate to severc AD. Significant differences in AOC were found between subgroups. The different correlations between cognitive impainnent of subgroups of subjects with the oxidative stress profilc are discussed in the context of AD pathogenesis.