Higher thyroid-stimulating hormone level may delay dementia progression in patients without thyroid dysfunction

Although thyroid dysfunction causes reversible cognitive impairment, the role of thyroid-stimulating hormone (TSH) variation within the normal range in dementia progression remains unclear.

To evaluate the association between baseline euthyroid TSH levels and cognitive decline rate in dementia patients.

We conducted a retrospective cohort study using Taiwan's Ditmanson Research Database (2015-2022). Dementia patients with normal thyroid function who initiated anti-dementia medication were included; those with overt thyroid disease, malignancy, or CNS infections were excluded. Baseline TSH (within 180 days prior to treatment) was stratified by the cohort median (1.392 μIU/mL) into Low and High TSH groups. Longitudinal cognitive outcomes were tracked via repeated Mini-Mental State Examination (MMSE) scores over 3 years. Generalized estimating equation (GEE) models evaluated the TSH-cognitive decline association, adjusting for age, sex, baseline MMSE, medication class, and vascular comorbidities.

A total of 402 patients (955 MMSE observations) were analyzed. Baseline characteristics were comparable between groups. In adjusted analyses, the Low TSH group declined by 1.44 MMSE points per year (95% CI: -1.90 to -0.97; p < 0.001). A significant time-by-TSH group interaction (beta = 0.76, 95% CI: 0.17 to 1.34; p = 0.011) indicated a slower annual decline in the High TSH group (-0.68 points/year).

Among euthyroid dementia patients, higher baseline TSH levels within the reference range were associated with significantly slower cognitive decline. These findings suggest physiological TSH variations may influence neurodegenerative progression, warranting further prospective research to clarify causality.