Review: The potential for estrogens in preventing Alzheimer's disease and vascular dementia

Simpkins, James W.; Perez, Evelyn; Wang, Xiaofei; Yang, Shaohua; Yi, Wen; Singh, Meharvan

doi:10.1177/1756285608100427

Cited by 73 publications

(45 citation statements)

References 242 publications

(338 reference statements)

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“…Therefore, females experience higher age-specific AD death rates [49]. It is reported that estrogen has a profound effect on altering AD progression [50] with nearly complete loss of estrogen following menopause related to AD in women [51]. Lower levels of estrogen in women with AD have been reported during the various endocrinological evaluations [52, 53].…”

Section: Endocrinal Dysregulations In the Ad Pathophysiologymentioning

confidence: 99%

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

Ahmad

Fatima

Mondal³

2019

Neuropsychobiology

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Alzheimer’s disease (AD), the commonest progressive neurodegenerative disorder of the brain, is clinically characterized by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Recent studies suggest a relationship between the endocrinal dysregulation and the neuronal loss during the AD pathology. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis regulating circulating levels of glucocorticoid hormones has been implicated in the pathophysiology of AD. Likewise, dysregulated insulin signaling, impaired glucose uptake and insulin resistance are some of the prime factors in the onset/progression of AD. In this review, we have discussed the changes in HPA and HPG axes, implicated insulin resistance/signaling and glucose regulation during the onset/progression of AD. Therefore, simultaneous detection of these endocrinal markers in the early or presymptomatic stages may help in the early diagnosis of AD. This evidence for implicated endocrinal functions supports the fact that modulation of endocrinal pathways can be used as therapeutic targets for AD. Future studies need to determine how the induction or inhibition of endocrinal targets could be used for predictable neuroprotection in AD therapies.

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Section: Endocrinal Dysregulations In the Ad Pathophysiologymentioning

confidence: 99%

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

Ahmad

Fatima

Mondal³

2019

Neuropsychobiology

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“…In general, although not always, CPS increases depressive and anxious behavior to a greater extent in female offspring, but impairs cognition more in the males [38,39]. Further, estrogens could prevent the processing of A␤PP into A␤ and reduce the tau hyperphosphorylation [22]. Which is why male offspring were used in this study.…”

Section: Discussionmentioning

confidence: 99%

“…7D for more details). Two-way ANOVA analyses showed that both CPS and COS significantly increased A␤ 42 protein (F (1,22) = 7.307, p = 0.013 for CPS; F (1,22) = 25.202, p < 0.001 for COS). Post hoc analyses revealed a significant increase in hippocampal A␤ 42 in the CPS + COS group, compared to all other groups (p < 0.001 for Control, p = 0.020 for COS-treated, p = 0.001 for CPS-treated).…”

Section: Expression Of Aβ 42 Protein Detected By Elisamentioning

confidence: 98%

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The Synergistic Roles of the Chronic Prenatal and Offspring Stress Exposures in Impairing Offspring Learning and Memory

Tang

Cheng

Wang

et al. 2016

JAD

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Abstract. In Alzheimer's disease (AD), extensive experimental studies have demonstrated a negative impact of chronic stress during various stages of life (including prenatal phase) on some aspects of AD pathology. Nevertheless, presently, few studies have been involved in the learning and memory impairments, as well as neuropathology elicited by the chronic prenatal stress (CPS) and the chronic offspring stress (COS) exposures simultaneously, particularly for the adult male APPswe/PS1dE9 murine offspring. Therefore, the aim of the present study was to investigate the influence of CPS on learning and memory impairments induced by COS in 6-month-old male APPswe/PS1dE9 offspring mice and the related mechanism. Our study firstly demonstrates that 14-day exposure to CPS could exacerbate the learning and memory impairments, as well as neuropathological damages in the CA3 regions of the hippocampus and cortex neurons, which is induced by the 28-day exposure to COS in 6-month-old male APPswe/PS1dE9 offspring mice. In addition, CPS could potentiate the production of A␤PP, A␤ 42, and corticosterone in 6-month-old male APPswe/PS1dE9 offspring that also suffer COS. In conclusion, our novel findings strongly implicate the synergistic roles of the CPS and COS exposures in impairing offspring learning and memory. Moreover, CPS potentiating the production of A␤ 42 might be mediated by glucocorticoids through increasing the expression of APP and BACE1 gene.

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“…Prior to publications of the Women’s Health Initiative (WHI) and Women’s Health Initiative Memory Study (WHIMS) (39)(40) (41)(42), hormone therapy (HT) was thought to be neuroprotective and a large body of basic science and generally supportive epidemiological evidence suggested that HT reduced the risk of Alzheimer’s Disease (AD) by approximately 50% (see reviews (43) (44)). Approach to hormone therapy (HT) changed radically however, following the results of the WHI and WHIMS.…”

Section: Implications Of the Whims Studymentioning

confidence: 99%

Effects of hormone therapy on cognition and mood

Fischer

Gleason

Asthana

2014

Fertility and Sterility

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Objective Results of the Women’s Health Initiative (WHI) and Women’s Health Initiative Memory Study (WHIMS) suggested that hormone therapy (HT) may be detrimental to cognitive health. This article reviews clinical studies which address issues relevant to those results. Design A search of PubMed and Web of Science was conducted using the search terms HT and cognition, HT and mood. Clinical and observational studies were selected if they were published after the year 2000. Theories of HT mechanisms of action, pharmacology, biology, and observational and clinical trials are discussed. Results While observational and clinical trials show conflicting findings, methodological considerations must be acknowledged. HT formulation and dose, route of administration, timing of initiation, length of treatment, and health of participants all contribute to inconsistencies in results. Transdermal estradiol and micronized progesterone administered at time of menopause are generally associated with cognitive and affective benefit. Conclusions At the present time, results from existing studies are equivocal regarding the benefits of HT on cognition and affect. Future studies, such as the Kronos Early Estrogen Prevention Study (KEEPS) should address methodological inconsistencies in order to provide clearer answers to this important question.

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Review: The potential for estrogens in preventing Alzheimer's disease and vascular dementia

Cited by 73 publications

References 242 publications

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

The Synergistic Roles of the Chronic Prenatal and Offspring Stress Exposures in Impairing Offspring Learning and Memory

Effects of hormone therapy on cognition and mood

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