Table 1.
Overview of results of clinical studies investigating the relationship between ERα and pathological and non-pathological age-related cognitive decline
| Relationship | Authors | Reported Population | Measures | Summary of findings | PMID/doi |
|---|---|---|---|---|---|
| Studies supporting an association between ERα/Esr1 and cognitive outcomes | Bojar et al. 2016 | Middle-aged women without dementia | Cognitive tests; E2 levels; Esr1 polymorphisms | Esr1 polymorphism modulated the effect of E2 on cognitive function | PMID: 27680398 |
| Cheng et al. 2014 | Meta-analysis of other studies | Esr1 SNPs Pvull and Xbal; AD risk | Esr1 Pvull SNP significantly increases risk of AD in Caucasian, but not Asian women | PMID: 25061285 | |
| Corbo et al. 2006 | AD patients and age-matched controls (men and women) | Esr1 SNPs Pvull and Xbal; APOE plasma levels | Esr1 SNPs Pvull and Xball increased risk of AD in men only; in women those SNPs increased rate of cognitive decline | PMID: 16699281 | |
| Hu et al. 2003 | AD patients and age-matched controls (women) | ERα localization in hippocampus | Decreased nuclear ERα staining in CA1 and CA2 of AD brains | PMID: 12819990 | |
| Ishunina et al. 2007 | AD patients and age matched controls (women) | Esr1 mRNA and aromatase activity in hippocampus | Decreased Esr1 mRNA (normal and splice variant) and decreased aromatase expression in AD hippocampi | PMID: 17010478 | |
| Kelly et al. 2008 | AD patients (men and women) | Cognitive tests; ERα protein levels | Increased nuclear ERα in frontal cortex associated with better cognitive performance | PMID: 18288931 | |
| Ma et al. 2009 | AD patients and age-matched controls (men and women) | Esr1 SNPs; AD risk | Several Esr1 SNPs associated with AD risk and age of onset | PMID: 19586561 | |
| Ma et al. 2014 | Elderly men and women | Esr1 SNPs; Cognitive tests | Several Esr1 polymorphisms associated with cognitive decline | PMID: 23567436 | |
| Pinkas et al. 2018 | Post-menopausal women | Esr1 and APOE polymorphisms; cognitive tests | Interactive effects with certain Esr1 and APOE polymorphisms on memory | doi.org/10.5114/aoms.2018.72972 | |
| Ryan et al. 2014 | Elderly men and women | Esr1 polymorphisms; Risk of AD and dementia | Esr1 polymorphism slightly assoc. with increased AD risk in women, but Esr1 polymorphism + APOE ε4 allele increased risk of AD | PMID: 23491264 | |
| Yaffe et al 2002 | Elderly women | Cognitive tests; Esr1 SNPs | Esr1 SNPs increase risk of cognitive impairment, independent of estrogen use | PMID: 11955468 | |
| Yaffe et al. 2009 | Elderly men and women without dementia | Cognitive tests; Esr1 and Esr2 SNPs | Esr1 and Esr2 SNPs increased risk of cognitive impairment | PMID: 17889406 | |
| Studies not supporting an association between ERα/Esr1 and cognitive outcomes | Fehsel et al. 2016 | Elderly women without dementia | Cognitive tests; Esr1, Esr2, APOE SNPs | No association of Esr1 SNPs with cognitive effects but did see effects for Esr2 and some interaction of Esr2 with APOE SNPs | PMID: 27629499 |
| Goumidi et al. 2011 | AD patients and age-matched controls (men and women) | Esr1 and Esr2 SNPs; late onset AD risk | No association of Esr1 or Esr2 SNPs with late onset AD risk | PMID: 21673408 | |
| Ryan et al. 2013 | Elderly women without dementia | Cognitive tests; Esr1 and Esr2 polymorphisms | Five common Esr1 polymorphisms not associated with cognitive impairment, but some effect of Esr2 polymorphisms | PMID: 23932494 |