Neurocognitive effects of subclinical thyroid disease

亚临床甲状腺疾病的神经认知影响

• 批准号: 6683420
• 负责人: MARY H SAMUELS
• 金额: $ 15.1万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6683420
• 关键词: age difference; clinical research; clinical trials; cognition; disease /disorder model; dosage; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; human therapy evaluation; hypothyroidism; memory; model design /development; neuropsychological tests; outcomes research; patient oriented research; quality of life; thyroid disorder; thyroxine; young adult human (21-34)

DESCRIPTION (provided by applicant): This Pilot and Feasibility Program (R-21) application represents a new research direction for the investigator, Dr. Mary Samuels, in the field of cognitive effects of mild (or "subclinical") thyroid disease in the adult human. 5% of the general population has subclinical thyroid disease, as defined by isolated TSH abnormalities, and 20% of older women have mild hypothyroidism (isolated TSH elevations). Therefore, the question of whether subclinical thyroid disease alters cognition has important public health implications. If subclinical thyroid disease were associated with cognitive deficits, this would be an important treatment indication. This is especially relevant to the older population, which has high rates of incipient dementia that could be worsened by the addition of cognitive deficits due to mild thyroid disease. In order to investigate this question, the investigator has designed a new model of experimentally-induced subclinical thyroid disease, and proposes a series of experiments to test and refine this model. Subjects who are currently taking L-thyroxine (L-T4) for chronic replacement therapy will be randomized to their usual doses of L-T4, vs. slightly lower doses (to induce mild subclinical hypothyroidism), or slightly higher doses (to induce mild subclinical hyperthyroidism). Treatment assignment is randomized, placebo-controlled, and double-blinded. Each treatment arm is designed to last 3 months. At the beginning and end of each arm, a battery of cognitive tests is administered. The specific cognitive outcome measures have been chosen to target cognitive domains most likely to be affected by mild thyroid disease. Throughout the studies, subjects are also monitored for safety, quality of life, mood, and other effects of altered thyroid function. The broad specific aims of this application are: 1) To develop and refine a model of experimentally-induced subclinical thyroid disease by testing dose increments of L-T4 in subjects receiving L-T4 replacement therapy; 2) To utilize the model to obtain pilot data on cognitive effects induced by subclinical hypothyroidism in younger and older human subjects; and 3) To utilize the model to obtain pilot data on cognitive deficits induced by subclinical hyperthyroidism in older subjects. Based on these pilot studies, it is the long-term goal of the investigator to investigate specific cognitive effects of altered thyroid status in the adult human.

描述（由申请人提供）：本试点和可行性计划（R-21）申请代表了研究者玛丽塞缪尔博士在成人轻度（或“亚临床”）甲状腺疾病认知影响领域的新研究方向。5%的普通人群有亚临床甲状腺疾病，定义为孤立的TSH异常，20%的老年妇女有轻度甲状腺功能减退症（孤立的TSH升高）。因此，亚临床甲状腺疾病是否改变认知的问题具有重要的公共卫生意义。如果亚临床甲状腺疾病与认知缺陷相关，这将是一个重要的治疗指征。这与老年人尤其相关，老年人早期痴呆症的发病率很高，由于轻度甲状腺疾病导致的认知缺陷可能会恶化。 为了研究这个问题，研究者设计了一个新的实验诱导的亚临床甲状腺疾病模型，并提出了一系列的实验来测试和完善这个模型。目前正在服用L-甲状腺素（L-T4）进行长期替代治疗的受试者将随机分配至其L-T4的常规剂量，与略低剂量（诱导轻度亚临床甲状腺功能减退）或略高剂量（诱导轻度亚临床甲状腺功能亢进）相比。治疗分配是随机、安慰剂对照和双盲的。每个治疗组设计持续3个月。在每组开始和结束时，进行一系列认知测试。选择特定的认知结局指标，以针对最有可能受轻度甲状腺疾病影响的认知领域。在整个研究过程中，还监测受试者的安全性、生活质量、情绪和甲状腺功能改变的其他影响。本申请的广泛具体目的是：1）通过在接受L-T4替代疗法的受试者中测试L-T4的剂量增量，开发和完善实验诱导的亚临床甲状腺疾病的模型; 2）利用该模型获得关于亚临床甲状腺功能减退症在年轻和老年人类受试者中诱导的认知效应的初步数据;利用该模型获得老年人亚临床甲状腺功能亢进症所致认知功能障碍的初步数据。基于这些初步研究，研究者的长期目标是研究成年人甲状腺状态改变的特定认知影响。