Neurocognitive effects of subclinical thyroid disease

描述（由申请人提供）：该试点和可行性计划（R-21）申请代表了研究者Mary Samuels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（孤立的TSH升高）。因此，亚临床甲状腺疾病是否会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。这与老年人群尤其相关，因为老年人群的早期痴呆率很高，而轻度甲状腺疾病导致的认知缺陷可能会使痴呆症恶化。

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.