Hogervorst Eef, Huppert Felicia, Matthews Fiona E, Brayne Carol
Department of Human Sciences, Brockington building, Loughborough University, LE11 3TU Loughborough, UK.
Psychoneuroendocrinology. 2008 Aug;33(7):1013-22. doi: 10.1016/j.psyneuen.2008.05.008. Epub 2008 Jul 21.
Hypothyroidism and subclinical hyperthyroidism have both been associated with cognitive impairment and dementia. The association between thyroid stimulating hormone (TSH), free thyroid hormone or thyroxine (FT4) levels and cognition was investigated at baseline and after a 2 year follow-up in 1047 participants over 64 years of age, without physical frailty or severe cognitive impairment at baseline. Results indicated that high log transformed TSH levels were associated with lower MMSE performance (B=-0.24 (S.E.=0.09), 95% CI=-0.41 to -0.07) at baseline, independent of FT4, age, sex, education and mood, and, in separate analyses, cardiovascular (risk) factors. Importantly, half of all hypothyroid cases were untreated and unaware of having this disorder. In analyses which excluded cases with thyroid disorders, stroke and those suspected of possible dementia/cognitive impairment (MMSE less than 25) or psychiatric mood disorders at baseline, high-normal FT4 levels were associated with worse MMSE performance and a greater risk for a drop of at least 4 points on the MMSE after 2 years (per pmol/l O.R.=1.13, 95% C.I.=1.03-1.22). In conclusion, elderly patients with cognitive impairment should always be assessed for hypothyroidism. It is unclear why high normal FT4 levels were independently associated with accelerated cognitive decline in those without overt thyroid disease. Other studies found that thyroxine can generate oxidative stress and damage neurons. Treatment with thyroxine in those without thyroid disease (as is sometimes done in anti-ageing clinics) is thus not recommended on the basis of these data and the optimal therapeutic level in the elderly may be lower than is assumed.
甲状腺功能减退症和亚临床甲状腺功能亢进症均与认知障碍和痴呆有关。在1047名64岁以上的参与者中，于基线期及2年随访后，对促甲状腺激素（TSH）、游离甲状腺激素或甲状腺素（FT4）水平与认知之间的关联进行了研究。这些参与者在基线期无身体虚弱或严重认知障碍。结果表明，在基线期，经对数转换的高TSH水平与较低的简易精神状态检查表（MMSE）评分相关（B=-0.24（标准误=0.09），95%置信区间=-0.41至-0.07），独立于FT4、年龄、性别、教育程度和情绪，且在单独分析中独立于心血管（风险）因素。重要的是，所有甲状腺功能减退病例中有一半未接受治疗且未意识到自己患有该疾病。在排除基线期患有甲状腺疾病、中风以及疑似可能患有痴呆/认知障碍（MMSE低于25）或精神情绪障碍的病例的分析中，高正常FT4水平与较差的MMSE评分相关，且在2年后MMSE至少下降4分的风险更大（每皮摩尔/升，比值比=1.13，95%置信区间=1.03-1.22）。总之，认知障碍的老年患者应始终接受甲状腺功能减退症的评估。目前尚不清楚为何在无明显甲状腺疾病的人群中，高正常FT4水平会独立与加速的认知衰退相关。其他研究发现，甲状腺素可产生氧化应激并损害神经元。基于这些数据，不建议在无甲状腺疾病的人群中使用甲状腺素进行治疗（抗衰老诊所有时会这样做），且老年人的最佳治疗水平可能低于目前的认知。
