ROLE OF REDUCED GLUTATHIONE, NITRIC OXIDE AND SOME TRACE ELEMENTS IN ALZHEIMERS DISEASE AND VASCULAR DEMENTIA

Dementia is an acquired impairment of intellectual and memory functioning. Oxidative stress is thought to be associated with the majority subtypes of dementia; Alzheimer s disease (AD) and vascular dementia (VaD), as well as type II diabetes mellitus. The current study was performed to investigate the hypothesis of decreased activity of antioxidant defense system protecting tissues from free radical damage in patients with AD and VaD by measuring the levels of reduced glutathione, nitric oxide, and some trace elements neurotoxicity, also to evaluate the association of diabetes mellitus as a risk for Alzheimer s disease. This study included 20 healthy subjects as control group (group I, consisted of 14 males and 6 females; mean age 75.8 ± 0.78 years), 20 patients were diagnosed as Alzheimer disease (group II, consisted of 8 males and 12 females; mean age 74.45 ± 0.44 years), 10 patients has Alzheimer disease with type II diabetes (group III, consisted of 7 males and 3 females; mean age 74.3 ± 1.02 years) and 10 patients were diagnosed as having vascular dementia (group IV, consisted of 4 males and 6 females; mean age 75.4 ± 1.77 years). The following plasma parameters were measured and compared among subject groups: reduced glutathione (GSH), nitric oxide (NO), copper, zinc, iron and blood hemoglobin. The results showed that GSH concentration was significantly decreased in the dementia groups compared to control group, whereas level of NO was significantly increased in dementia groups in comparison to controls, however, the level was markedly increased in Alzheimer disease with type II diabetes mellitus. Furthermore, the copper level was significantly increased in AD and VaD than control group at P 0.001. The results revealed non-significant elevation in plasma content of Zn in dementia groups versus controls. Plasma iron concentration was significantly lower in dementia groups when compared to the controls (P 0.0001), and its level was positively correlated with hemoglobin level (r = 0.722, P = 0.019) in VaD. It can be concluded that, the reduced levels of GSH, hemoglobin and iron along with the elevated levels of NO and copper are significantly associated with the development of AD which supports the hypothesis that decreased activity of antioxidant defense system is associated with excessive free radical production that has the potential of augmenting neuron degradation observed in this disease. Also, anemia and diabetes mellitus increase the risk of dementia, particularly in VaD and the disturbance in trace elements are all involved in the disease pathogenesis. Therefore, we may suggest that die administration of free radical scavengers and iron could provides a therapeutic inroad in the fight against dementia.