دانلود رایگان مقاله انگلیسی اپیدمیولوژی استروژن و زوال عقل در زنان مبتلا به سندرم داون - الزویر 2018

ABSTRACT

Several lines of investigation have shown a protective role for estrogen in Alzheimer's disease through a number of biological actions. This review examines studies of the role of estrogen-related factors in age at onset and risk for Alzheimer's disease in women with Down syndrome, a population at high risk for early onset of dementia. The studies are consistent in showing that early age at menopause and that low levels of endogenous bioavailable estradiol in postmenopausal women with Down syndrome are associated with earlier age at onset and overall risk for dementia. Polymorphisms in genes associated with estrogen receptor activity and in genes for estrogen biosynthesis affecting endogenous estrogen are related to age at onset and cumulative incidence of dementia, and may serve as biomarkers of risk. To date, no clinical trials of estrogen or hormone replacement therapy (ERT/HRT) have been published for women with Down syndrome. While findings from clinical trials of ERT or HRT for dementia have generally been negative among women in the neurotypical population, the short interval between menopause and onset of cognitive decline, together with a more positive balance between potential benefits and risks, suggests an opportunity to evaluate the efficacy of ERT/HRT for delaying or preventing dementia in this high risk population, although questions concerning the optimal formulation and timing of the hormone therapy are not yet resolved.

7. Estrogen or hormone replacement therapy

Among women in the neurotypical population, epidemiologic studies have shown that estrogen replacement therapy or hormone replacement therapy more generally (ERT/HRT) was associated with slower declines in cognitive function in postmenopausal women, particularly in verbal memory, and decreased risk of AD has also been shown in some studies [27,131–141], but others have not shown a benefit [142,143]. The association between ERT/HRT and risk of AD may vary depending on both the formulation and timing of usage [118,144]. A recent analysis of HRT use among women in the Finnish population from 1995 to 2011 found that use of estrogen plus progestogen was associated with an increased risk of AD, while long term use of estrogen alone was associated with reduced risk [145] and this difference in formulation may be related to the inconsistent results in the epidemiologic studies. The Cache County Study of women in the neurotypical population found evidence that use of HRT in the perimenopausal period protected against AD, while use of HRT among elderly women did not protect against AD unless initiated before age 63 [118,141], suggesting that there may be a critical period during which HRT provides protective effects on cognitive function, possibly early in the perimenopausal period or just after menopause [37,146–148].