Estradiol and hormone therapy: Associations with cognitive and behavioural changes in postmenopausal females
Bibliographic record
Abstract
Abstract Background Estradiol is an ovarian hormone present during reproductive years. During menopause, estradiol decline may trigger or exacerbate pathological mechanisms of AD. Estrogen‐based hormone therapies (HT), may mitigate cognitive decline and AD, although findings are inconsistent. Alongside later‐life emergent and persistent cognitive changes, later‐life emergent and persistent behavioural and personality changes (i.e., mild behavioral impairment ‐ MBI), is an early marker of dementia, but its relationship with estradiol is unknown. This study examined relationships between postmenopausal estradiol levels, HT‐use, and cognitive and behavioural symptoms. Method Participant data were from the Comprehensive Assessment of Neurodegeneration and Dementia study, including 333 postmenopausal females ( n = 97 used HT) spanning the neurocognitive spectrum. Estradiol levels were measured from blood plasma samples. Cognition was assessed using the Montreal Cognitive Assessment (MoCA); scores ≥26 were considered normal cognition. MBI symptoms were measured with the Mild Behavioral Impairment Checklist (MBI‐C); higher scores denoted greater symptom severity. Associations between estradiol levels and MoCA and MBI‐C scores were analyzed using linear and negative‐binomial regressions, respectively, including an estradiol*HT‐use interaction term. All models were adjusted for age, education, race, HT‐use, age at menopause onset, and type of menopause (spontaneous, oophorectomy, hysterectomy, other reasons). Result Participants (mean age 71.3±6.8 years) included 27.0% cognitively normal, 23.7% with subjective cognitive decline, 34.5% with mild cognitive impairment, and 14.7% with dementia. Neurocognitive status did not predict estradiol levels. Estradiol levels were not associated with MoCA score (b=0.29, 95%CI [‐1.00, 0.42], p = 0.66) and the relationship was not modified by HT‐use (b int =1.41, 95%CI [‐0.11, 2.93], p = 0.16). HT‐use was not independently associated with MoCA score (b=0.79, 95%CI [‐0.24, 1.83], p = 0.2). However, higher estradiol levels were associated with lower (i.e., better) MBI‐C scores (b=0.51, 95%CI [0.28, 0.94], p = 0.05), independent of HT‐use (b int =0.96, 95%CI [0.22, 4.05], p = 0.95). Notably, HT‐use was independently associated with lower MBI‐C scores (b=0.24, 95%CI [0.11, 0.55], p <0.01). Conclusion Higher estradiol levels and HT‐use were independently associated with lower MBI symptom severity but not better MoCA scores, suggesting neuropsychiatric markers such as MBI may be more sensitive to postmenopausal estradiol changes than cognitive assessments. However, longitudinal biomarker studies are needed to elucidate underlying mechanisms.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".