Oestrogen Alpha-Receptor Variant and Two-Year Memory Decline in Midlife Australian Women

Bousman, Chad A.; Szoeke, Cassandra; Chen, Karren; Dennerstein, Lorraine; Henderson, Victor W.; Everall, Ian

doi:10.1159/000341879

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…In addition the results of our early work have highlighted the importance of longitudinal studies in cognitive research as timing and duration of exposures is relevant to outcomes for blood pressure [140], lipids [141], hormones [142–146] and other modifiable risk factors [142]. Genomic associations with early cognitive decline have been examined with the influence of estrogen polymorphism published [147]. There is an absence of published normative data in Australia and the first published normative papers came from the WHAP data set for memory [148] and executive function [149].…”

Section: Resultsmentioning

confidence: 99%

Cohort profile: Women’s Healthy Ageing Project (WHAP) - a longitudinal prospective study of Australian women since 1990

Szoeke

Coulson

Campbell

et al. 2016

womens midlife health

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Background: The cohort was commenced to examine women's health from midlife (45-55 years) before the menopausal transition and into ageing. Methods: Randomised selection and assessment of 2,001 women living in the Melbourne metropolitan area was conducted by the Roy Morgan Centre in 1990/91. Of the 779 women who met the entry criteria for the longitudinal follow-up (aged 45-55 years, menstruating, having a uterus and at least one ovary and not taking hormone therapy) 438 agreed to be seen annually across the menopausal transition from 1992 to 1999. Longitudinal prospective follow-up since 2000 has continued intermittently (2002/03, 2004/05, 2012/13, 2014/15). Data collection has included fasting biomarkers in each year since 1992, clinical assessment, lifestyle and quality of life data, physical measures and validated questionnaire data. Participants have consented to data linkage and, to date, mammogram and BioGrid data have been accessed. Biobank storage including serum, deoxyribonucleic acid (DNA) storage and PAXgene tubes are maintained. Discussion: The WHAP has contributed to over 200 published research findings, several books, and book chapters in a variety of areas, including: health and wellbeing; mental and cognitive health; bone health; lifestyle, vascular risk and prevention; women's health and hormonal transition; and cross-cultural research. With all participants now aged over 70 years, the cohort is ideally placed to answer key questions of healthy ageing in women. With more than 25 years of longitudinal prospective follow-up this Australian dataset is unique in its duration, breadth and detail of measures including clinical review and specialized disease-specific testing and biomarkers. Ongoing follow-up into older ages for this long-running cohort will enable the association between mid to late-life factors and healthy ageing to be determined. This is particularly valuable for the examination of chronic diseases which have a 20-30 year prodrome and to provide knowledge on multiple morbidities. The dataset has a unique opportunity to improve our understanding of temporal relationships and the interactions between risk factors and comorbidities.

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Section: Resultsmentioning

confidence: 99%

Cohort profile: Women’s Healthy Ageing Project (WHAP) - a longitudinal prospective study of Australian women since 1990

Szoeke

Coulson

Campbell

et al. 2016

womens midlife health

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“…A study by Bousmann, which included women aged 56–67, showed that the carriers of TT PvuII obtained the worst results for logical memory, compared to those with CC PvuII, who obtained the best results. The researcher postulates the necessity for further studies in order to prove the hypothesis that the T PvuII allele is the genetic marker of memory disorders [ 46 ]. Yaffe found a significant relationship between A Xbal and/or T PvuII polymorphisms, and lower results for cognitive functions in the Modified Mini-Mental Status Examination (3MS).…”

Section: Discussionmentioning

confidence: 99%

Cognitive Functions, Concentration of Endogenous Estradiol, Estrogen Receptor α (ERα) Polymorphism in Postmenopausal Women

et al. 2016

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BackgroundThe goal of this study was to investigate the relationship between cognitive functions and the level of endogenous estradiol in postmenopausal women, according to which estrogen receptor α (ERα) polymorphism the woman carries.Material/MethodsThe study group consisted of 210 women. The inclusion criteria were: minimum 2 years after the last menstruation, FSH concentration 30 U/ml, and no dementia signs on Montreal Cognitive Assessment (MoCA). A computerized battery of Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. Genotyping of the ERα polymorphism was performed using a polymerase chain reaction and restriction enzymes (PCR-RFLP). Blood plasma was tested for FSH and estradiol (E2). Statistical analysis was performed using STATISTICA software.ResultsA relationship was confirmed between standard scores for 3 cognitive functions: general memory, verbal memory, and processing speed, and the XbaI polymorphism in the women in the study. In the group of women with genotype TT PvuII, significant positive relationships were observed between the concentration of E2 and the standard scores of 3 cognitive functions: general memory, verbal memory, and processing speed. In the group of women with genotype TC PvuII, significant negative correlations were found between the concentration of E2 and the standard scores of 4 cognitive functions: NCI, general memory, verbal memory, and processing speed.ConclusionsERα polymorphism exerted an effect on the interaction between the concentration of estradiol and the results for cognitive functions. The concentration of estradiol did not depend on Xba1 and PvuII polymorphisms. The results for cognitive functions depended on which Xba1 polymorphism the woman carried.

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“…The results obtained depended on demographic factors, concomitant diseases, presence of APOE e*4, cigarette smoking and alcohol consumption. In the researcher’s opinion, they are also evidence indicating the need for further studies to confirm that the presence of the T allele of PvuII is a genetic marker of the risk of memory disorders among postmenopausal women [ 80 ]. Sundermann conducted a comprehensive meta-analysis including 14 studies of this issue.…”

Section: Cognitive Functions According To Erα Polymorphisms – Effect mentioning

confidence: 99%

Does genetic testing for ERα gene polymorphisms provide new possibilities of treatment for cognitive function disorders in postmenopausal women?

Gujski

Pinkas

Wierzbińska-Stępniak

et al. 2017

aoms

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It is commonly considered that cognitive abilities decrease with age, especially with respect to processing and psychomotor speed. It is an interesting issue whether, apart from the ageing process, the undergoing of menopause itself deteriorates cognitive functions, compared to women at reproductive age. Hopes for improvement of cognitive functions were pinned on the use of menopausal hormone therapy. However, the results of studies concerning the effect of hormone replacement therapy on cognition proved to be contradictory. It seems that the essence of the problem is more complicated than only estrogen deficiency. It is suggested that estrogen receptor α (ERα) polymorphism may be responsible for the differences in the effect of estrogens on cognitive processes. The article presents current knowledge concerning the effect of estrogens on the central nervous system, especially the role of ERα polymorphism, with respect to foreseeing benefits from the use of exogenous estrogens for cognitive functions. At the present stage of research, ERα appears to be poorly specific; nevertheless, it may be an important instrument for the classification of peri- and post-menopausal patients in the group where therapy with the use of estrogens may bring about benefits in terms of prevention and treatment of cognitive disorders. It also seems necessary to conduct prophylactic, screening examination of cognitive functions in post-menopausal women, in order to identify those at risk of the development of dementia.

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Oestrogen Alpha-Receptor Variant and Two-Year Memory Decline in Midlife Australian Women

Cited by 4 publications

References 56 publications

Cohort profile: Women’s Healthy Ageing Project (WHAP) - a longitudinal prospective study of Australian women since 1990

Cohort profile: Women’s Healthy Ageing Project (WHAP) - a longitudinal prospective study of Australian women since 1990

Cognitive Functions, Concentration of Endogenous Estradiol, Estrogen Receptor α (ERα) Polymorphism in Postmenopausal Women

Does genetic testing for ERα gene polymorphisms provide new possibilities of treatment for cognitive function disorders in postmenopausal women?

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