P3-139: association between esr1 and cognition in adni cohort

Whilst women are more likely to develop dementia than age matched men, the role of estrogen on cognition is more complex than first observed. Most recent hypotheses indicate the timing of estrogen supplementation is important and with the positive results from hormone therapy in the ELITE trial [1]It is important to better understand the relationship between estrogen and cognition. Our prior research suggests that estrogen receptor (ESR1) polymorphisms are associated with memory impairment and cognitive decline [2]. All data for this project were sourced from the ADNI LONI database. ESR1 polymorphism data was extracted from WGS data. The WGS was searched for rs2234693 snip and classified positive if rs2234693 = TT or negative if TC or CC combination was observed. Cognitive changes were measured by memory and executive function composite scores at each follow-up. Mixed effect multilevel model was created to determine the impact of ESR1 polymorphism on cognitive changes while controlling for potential confounders. 577 participants (mean age 75.6±7.5 years, 45% female, 66% had AD/MCI) had data on ESR polymorphism (rs2234693) and cognitive function. 175 were found to be ESR1 Positive and 402 were ESR1 negative. While no associations were observed between ESR and cognitive decline in male (any age) or female age 70 and above, strong positive relationships were observed between ESR and cognitive changes in female age 69.9 and younger (β=0.36, 95%CI (0.02-0.70), p=0.039 for memory composite and β= 0.43, 95%CI (0.03-0.83), p=0.036 for executive function), while controlling for participants age and education level. Similar results were observed in a sub-cohort of female age 69.9 and younger who were diagnosed with AD/MCI. Our findings support the hypothesis that positive ESR1 plays an important protective role on cognitive decline in women under 70. It is important this relationship is further explored in the context of potential treatment.