Peripheral reductive capacity is associated with cognitive performance and survival in Alzheimer's disease
Journal of Neuroinflammation
Department of Cell Biology and Neurosciences, Section of Degenerative and Inflammatory Neurological Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; Neurology Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; The Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, Radcliffe Infirmary, Oxford, United Kingdom; Oxford Centre for Gene Function, Department of Physiology Anatomy and Genetics, Parks Rd., Oxford OX1 3PT, United Kingdom
Background: Oxidative stress is believed to be an early event and a key factor in Alzheimer's disease (AD) pathogenesis and progression. In spite of an intensive search for surrogate markers to monitor changes related to oxidative stress in the brain, there is as yet no consensus about which markers to use in clinical studies. The measurement of peripheral anti-oxidants is an alternative way of evaluating the involvement of oxidative stress in the course of the disease. Given the complexity of peripheral anti-oxidant defence, variations in the levels of individual anti-oxidant species may not fully reflect the overall capacity to fight oxidant conditions. We therefore chose to evaluate the total reductive capacity (herein defined as anti-oxidant capacity, AOC) in serum from control subjects and AD patients in order to study the association between peripheral antioxidant defence, cognitive impairment and patient survival. Methods: We measured the levels of AOC in serum samples from 26 cognitively normal controls and 25 AD patients (12 post-mortem confirmed) who completed the Cambridge Cognitive Assessment. Cognitive decline was assessed in a subgroup of 19 patients who underwent a second cognitive assessment 2 years after the initial visit. Results: Serum AOC levels were lower in AD patients than in controls and were correlated with their cognitive test scores, although AOC levels were unrelated to cognitive decline assessed two years later. On the other hand, AOC levels were predictive of the length of patients' survival, with higher levels giving longer survival. Conclusion: This study indicates that peripheral anti-oxidant defences are depleted in AD patients. The results suggest that serum AOC is a good index of the general health status and prognosis of patients but does not necessarily reflect the extent to which vulnerable neuronal populations are protected from oxidant processes. Further studies are required to establish whether peripheral AOC measurements may be useful in identifying asymptomatic individuals or those with early symptoms at high risk of developing significant cognitive impairment or dementia. © 2006 Minghetti et al; licensee BioMed Central Ltd.
antioxidant; adult; aged; Alzheimer disease; article; cognitive defect; controlled study; correlation analysis; disease association; disease course; disease marker; female; follow up; health status; high risk patient; human; major clinical study; male; mental performance; mental test; neuroprotection; oxidative stress; pathogenesis; prediction; prognosis; risk assessment; scoring system; serology; survival time