Một số các nghiên cứu kiểm tra giới tính như là một yếu tố nguy cơ AD tìm thấy một nguy cơ gia tăng ở phụ nữ, nhất là phụ nữ lớn tuổi, thậm chí sau khi kiểm soát mức độ giáo dục và các yếu tố khác, chẳng hạn như tỉ lệ sống sót khác biệt giữa các. | ALZHEIMER S DISEASE 197 VI. Estrogen Therapy A number of studies examining gender as a risk factor for AD find an increased risk in women especially older women even after controlling for education level and other factors such as differential survival rates. This led to the hypothesis that hormonal factors may play a role in determining susceptibility to AD. This suggestion is supported by the finding that postmenopausal women receiving hormone replacement therapy have a reduced risk of AD Paganini-Hill and Henderson 1994 1996 . A reduced risk of AD was also identified in the Baltimore Longitudinal Study of Aging a prospective study of the effect of estrogen replacement therapy on incident AD Kawas et al. 1997 . The mechanism by which estrogen protects from AD is unclear. It was suggested the mode of action is through estrogen-sensitive neurons in the hippocampus and cortex Maki and Resnick 2000 although evidence from ưansgenic mice showed that estrogen treatment increased the amount of the neuroprotective sAPP fragment but did not reduce the production of A 3 Vincent and Smith 2000 . Estrogen has also been shown to have antioxidant activity Niki and Nakano 1990 that may contribute to its protective role. Treatment of women with mild to moderate AD with estrogen for 1 year has not been found to improve cognitive function or slow the progression of the disease Mulnard et al. 2000 . Interestingly however nondemented subjects treated with estrogen have better cognitive performance and increased regional CBF than non treated subjects Maki and Resnick 2000 . This together with the epidemiological evidence of reduced risk of AD in subjects treated with estrogen suggests the benefits of estrogen are lost after the onset of AD. This is not surprising as the regions found to be sensitive to esưogen . hippocampus parahippocampus and temporal cortex Maki and Resnick 2000 are the areas of the brain that are damaged earliest and to the greatest degree in AD Braak and Braak .
