Sex-, and neurodegeneration-dependent effect modification in the association between thyroid function and cognitive impairment in non-depressed, non-demented elderly
DOI: 10.1101/2024.07.04.24309827
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Summary
This study investigates the association between thyroid function and cognitive impairment in non-depressed, non-demented elderly individuals, specifically examining whether sex and neurodegenerative status modify this relationship. Motivated by the complex, often controversial literature regarding thyroid-brain interactions and the higher prevalence of thyroid disorders in women, the authors sought to clarify if thyroid stimulating hormone (TSH) levels correlate with cognitive decline differently across sexes and diagnostic groups. The researchers conducted a cross-sectional analysis using baseline data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The final cohort included 1,845 participants (median age 73; 48% female) diagnosed as either healthy controls (HC) or having mild cognitive impairment (MCI). Participants with overt hypothyroidism (TSH ≥ 10 µIU/mL) or significant depression (Geriatric Depression Scale score ≥ 5) were excluded. Cognitive status was assessed using the Alzheimer’s Disease Assessment Scale–13-item (ADAS13) score. Statistical analyses included linear and logistic regression models, adjusted for age, sex, education, race, APOE ε4 status, and BMI. The study tested for non-linearity and stratified results by sex and neurodegenerative status. The results revealed no significant association between TSH levels and overall cognition in the total population. However, significant associations were observed exclusively in males. In men, higher TSH levels were significantly associated with lower ADAS13 scores (indicating better cognition), with an adjusted regression coefficient of -0.40 (95% CI: -0.74, -0.07; p=0.019). Conversely, no such association was found in females. Logistic regression indicated that higher TSH levels were associated with decreased odds of being diagnosed with MCI in the total population (adjusted OR: 0.87; p=0.002) and specifically in males (adjusted OR: 0.80; p=0.001). Sensitivity analyses using restricted cubic splines identified the median TSH value as a significant cutoff point for this association. The study concludes that the link between thyroid function and cognitive decline in the elderly is subject to sex-driven effect modification, with lower TSH levels associated with poorer cognitive outcomes only in men. These findings suggest that sex-specific biological mechanisms may influence how thyroid hormones affect cognition. The authors emphasize the need for separate analysis of males and females in future research and call for randomized longitudinal studies to establish causality and explore potential therapeutic interventions.
Provenance
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| Stage | Outcome | Tool | Model | Prompt | Attempts | Completed |
|---|---|---|---|---|---|---|
| discover | success | Crossref | — | — | 1 | 2026-06-18 |
| archive | success | unpaywall | — | — | 2 | 2026-06-25 |
| extract | success | cached | — | — | 2 | 2026-06-26 |
| clean | success | clean | — | — | 1 | 2026-06-18 |
| chunk | success | chunk | — | — | 1 | 2026-06-18 |
| embed | success | embed | Qwen/Qwen3-Embedding-8B | — | 1 | 2026-06-18 |
| promote | success | — | — | — | 1 | 2026-06-18 |
| summarize | success | llm | qwen3.6-27b-prismaquant | summ-v5 | 1 | 2026-06-26 |
| tag | success | vector_similarity | — | — | 6 | 2026-06-18 |
| verify | success | — | — | — | 1 | 2026-06-26 |
Summary generated by qwen3.6-27b-prismaquant on 2026-06-26; verification: verified.
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