Importance In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.

中文翻译：

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甲状腺功能障碍与认知功能的关联：个体参与者数据分析。

重要性 在临床指南中，明显和亚临床甲状腺功能障碍被认为是认知能力下降的原因和可治疗因素。然而，关于这些关联的科学文献显示出不一致的发现。目的评估基线甲状腺功能障碍与认知功能和痴呆的横断面和纵向关联。设计、设置和参与者 这项多队列个体参与者数据分析评估了 114267 人年（中位数，1.7-11.3 年）的认知功能随访和 525222 人年（中位数，3.8-15.3 年）的痴呆随访。 1989 年和 2017 年。认知功能分析包括 21 个队列，包括 38 144 名参与者。对痴呆症的分析包括 8 个队列，共有 2033 例痴呆症病例和 44 573 例对照组。数据分析于 2016 年 12 月至 2021 年 1 月进行。根据统一的促甲状腺激素截断值和研究特异性游离甲状腺素值，甲状腺功能分为明显甲状腺功能亢进、亚临床甲状腺功能亢进、甲状腺功能正常、亚临床甲状腺功能减退和明显甲状腺功能减退。主要结果和测量 主要结果是整体认知功能，主要使用简易精神状态检查进行测量。执行功能、记忆力和痴呆是次要结果。首先分别使用多变量线性回归和多变量 Cox 回归在研究水平上进行分析。这些研究与限制性最大似然荟萃分析相结合。为了克服使用不同量表的问题，将结果转换为标准化平均差。对于突发性痴呆，计算了风险比。结果 74 565 名参与者中，66 567 人（89.3%）甲状腺功能正常，577 人（0.8%）有明显甲亢，2557 人（3.4%）有亚临床甲亢，4167 人（5.6%）有亚临床甲减，697 人（0.9 %) 有明显的甲状腺功能减退。基线时特定研究的中位年龄从 57 岁到 93 岁不等；42 847 (57.5%) 名参与者是女性。甲状腺功能障碍与整体认知功能无关；显性甲状腺功能减退和甲状腺功能正常之间的差异最大：横断面（-0.06 标准化平均评分差；95% CI，-0.20 至 0.08；P = .40）和纵向（0.11 标准化平均差，每年下降幅度较大；95 % CI，-0.01 至 0.23；P = .09）。在甲状腺功能障碍与执行功能、记忆力或痴呆风险之间没有观察到一致的关联。结论和相关性 在这项对超过 74 000 名成年人的个体参与者数据分析中，亚临床甲状腺功能减退症和甲状腺功能亢进症与认知功能、认知能力下降或痴呆症无关。关于明显的甲状腺功能障碍在痴呆风险中的作用，无法得出严格的结论。这些发现不支持现行指南推荐的在老年人认知能力下降的情况下筛查亚临床甲状腺功能障碍的做法。亚临床甲状腺功能减退症和甲状腺功能亢进症与认知功能、认知能力下降或痴呆症无关。关于明显的甲状腺功能障碍在痴呆风险中的作用，无法得出严格的结论。这些发现不支持现行指南推荐的在老年人认知能力下降的情况下筛查亚临床甲状腺功能障碍的做法。亚临床甲状腺功能减退症和甲状腺功能亢进症与认知功能、认知能力下降或痴呆症无关。关于明显的甲状腺功能障碍在痴呆风险中的作用，无法得出严格的结论。这些发现不支持现行指南推荐的在老年人认知能力下降的情况下筛查亚临床甲状腺功能障碍的做法。