Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Medical School, University of Western Australia, Perth, Western Australia, Australia.
JAMA Intern Med. 2021 Nov 1;181(11):1440-1450. doi: 10.1001/jamainternmed.2021.5078.
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.
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.
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.
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.
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.
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.
在临床指南中，显性和亚临床甲状腺功能障碍被认为是认知能力下降的因果和可治疗因素。然而，关于这些关联的科学文献显示出不一致的结果。
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、地点和参与者：这项多队列个体参与者数据分析了 1989 年至 2017 年期间认知功能的 114267 人年（中位数，1.7-11.3 年）和痴呆的 525222 人年（中位数，3.8-15.3 年）随访。认知功能分析包括 21 个队列，共包含 38144 名参与者。痴呆分析包括 8 个队列，共有 2033 例痴呆病例和 44573 例对照。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，甲状腺功能被分类为显性甲状腺功能亢进、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显性甲状腺功能减退。
主要结局是全球认知功能，主要通过简易精神状态检查来衡量。次要结局是执行功能、记忆和痴呆。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了分析。这些研究通过受限极大似然法荟萃分析进行了合并。为了克服使用不同量表的问题，结果被转化为标准化均数差。对于新发痴呆，计算了风险比。
在 74565 名总参与者中，66567 名（89.3%）参与者甲状腺功能正常，577 名（0.8%）参与者患有显性甲状腺功能亢进，2557 名（3.4%）参与者患有亚临床甲状腺功能亢进，4167 名（5.6%）患有亚临床甲状腺功能减退，697 名（0.9%）患有显性甲状腺功能减退。基线时各研究的中位年龄从 57 岁到 93 岁不等；42847 名（57.5%）参与者为女性。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与甲状腺功能正常之间的差异最大（评分的 0.06 个标准化均数差；95%CI，-0.20 至 0.08；P=0.40）和纵向（每年认知功能下降 0.11 个标准化均数差异；95%CI，-0.01 至 0.23；P=0.09）。甲状腺功能障碍与执行功能、记忆或痴呆风险之间没有一致的关联。
在这项对超过 74000 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和甲状腺功能亢进与认知功能、认知能力下降或新发痴呆无关。对于显性甲状腺功能障碍在老年人大脑认知能力下降中的痴呆风险作用，不能得出严格的结论。这些发现不支持当前指南中建议的在认知能力下降的老年人群中筛查亚临床甲状腺功能障碍的做法。
