Translational and Clinical Research Institute, International Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom.
Endocrinology Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
Thyroid. 2021 Aug;31(8):1182-1191. doi: 10.1089/thy.2020.0596. Epub 2021 Jul 2.
Low serum thyrotropin (TSH) has been associated with an increased risk of cognitive impairment in observational studies of older individuals, but the mechanism underlying this is unclear. We investigated the association between changes in thyroid status and cognitive impairment in very old adults, using prospective data from the Newcastle 85+ study. A cohort of 85-year-old individuals was assessed for health status and thyroid function. Complete data from a comprehensive multidimensional measure of health and repeat thyroid function were available for 642 participants with normal free thyroid hormones and TSH levels ranging between 0.1 and 10 mU/L. Cognitive performance, assessed using Mini-Mental State Examination (MMSE) and Cognitive Drug Research battery was examined by using linear mixed, logistic regression, and Cox proportional hazard models in relation to baseline and 3-year changes in serum TSH, free thyroxine (fT4), and free triiodothyronine (fT3). Over 3 years, declining serum TSH was associated with reductions in fT4 and fT3, and an increased risk of incident cognitive impairment by 5 years (odds ratio1.77 [95% confidence interval: 1.19-2.61]; = 0.004). A greater reduction in MMSE score was associated with larger TSH decline, at 3 ( = 0.001) and 5 years ( < 0.001), respectively. Steady fT4 concentrations were found in participants with rising TSH. In contrast to physiological expectation, in this group of 85-year-olds, a declining serum TSH was associated with reductions in free thyroid hormones over time. A decreasing serum TSH trajectory over time anticipated cognitive decline in later life. Declining TSH concentrations are a biomarker for cognitive impairment in later life.
血清促甲状腺激素（TSH）水平降低与观察性研究中老年个体认知障碍风险增加相关，但其中的机制尚不清楚。我们使用纽卡斯尔 85+研究的前瞻性数据，研究了甲状腺状态变化与非常老年成年人认知障碍之间的关系。
对 85 岁的个体进行健康状况和甲状腺功能评估。共有 642 名游离甲状腺激素和 TSH 水平正常的参与者（游离甲状腺激素水平在 0.1 至 10 mU/L 之间），可获得全面多维健康测量和重复甲状腺功能的完整数据。使用 Mini-Mental State Examination (MMSE) 和 Cognitive Drug Research 电池评估认知表现，使用线性混合、逻辑回归和 Cox 比例风险模型，根据基线和 3 年 TSH、游离甲状腺素（fT4）和游离三碘甲状腺原氨酸（fT3）的变化，评估其与认知障碍的关系。
在 3 年内，血清 TSH 下降与 fT4 和 fT3 减少以及 5 年内发生认知障碍的风险增加相关（比值比 1.77 [95%置信区间：1.19-2.61]； = 0.004）。TSH 下降幅度越大，MMSE 评分下降幅度越大，分别在 3 年（ = 0.001）和 5 年（ < 0.001）。在 TSH 升高的参与者中发现 fT4 浓度稳定。
与生理预期相反，在这组 85 岁的老年人中，随着时间的推移，血清 TSH 降低与游离甲状腺激素减少相关。随着时间的推移，血清 TSH 下降轨迹预示着晚年认知能力下降。TSH 浓度下降是晚年认知障碍的生物标志物。
