Mechanism Of Cognitive Dysfunction And Replacement Therapy In Patient With Subclinical Hypothyroidism

Background Subclinical hypothyroidism (SCH) refers to patients with normal serum levels of thyroxine, but the plasma thyroid stimulating hormone(TSH) increased, around the world in the general population incidence of subclinical hypothyroidism reports vary. Canaris made a large epidemiological survey in Colorado of USA which randomly selected large sample of 25000 people,and observed their TSH levels and measured their symptoms. Canaris found in the sample 2,336 people was diagnosed with subclinical hypothyroidism about 3%～10.4% ,and the trend has increased.,especially in women, the elderly , those with other autoimmune diseases and the crowd in higher IDD areas. Subclinical hypothyroidism, the incidence increased with increasing age. It has been reported incidence rate is about 5% -10% in the elderly population. In women over 60 years old it is up to 20% (200% increase), and more than 16% of men 74 years of age.Subclinical hypothyroidism results in the cognitive impairment, including the impairment of learning and memory, selective attention during childhood and young adulthood. In addition, the older patients with Subclinical hypothyroidism show the reduced the capacity of learning, language fluency, attention and exercise. Subclinical hypothyroidism can also result in dyslipidemia, such as higher level of total cholesterol (TC),low-density lipoprotein (LDL) and lipoprotein-a, lower level of high-density lipoprotein (HDL) and damage to the cardiovascular system, which becomes one of the risk factors to the old artery atherosclerosis and myocardial infarction.Methods To systematic analysis the effect of Subclinical hypothyroidism on the cognitive function and the value of thyroid hormone replacement therapy, we selected children, the middle-aged and elder patients, with the same age, sex, education level as the patients screened for good general health. The subjects were evaluated for thyroid function, neuropsychological and functional magnetic resonance imaging test before and after 6 months 'treatment,Results 1.30 children patients who were frist diagnosed as SCH (1.1 boys and 19 girls,14 from city, 16 from rural, age between 8 to 16) had lower plasma thyroid hormone than the normal subjects before treatment,although thyroxines were in normal ranges. SCH children showed a significant and extensive C-WISC lower score on all tests in baseline than the same age and education controls.2.11 adult patients who were frist diagnosed as SCH (10 women and one man, all right-handed, aged between 18～47) had lower plasma T3, FT3, FT4 level than the 12 normal subjects (11 women and one man, all right-handed, aged between 20 and 40) before treatment, although thyroxines were in normal ranges. SCH patients showed no difference in total score by WMS-CR assessment of the memory ., SCH patients were lower accuracy rate than the normal subjects by the n-back task..3.50 elderly patients who were frist diagnosed as SCH had lower plasma FT3, FT4 level than the 25 volunteers with normal thyroid function for control, although thyroxines were in normal ranges. SCH patients was significantly lower total scores and attention, memory, and perception sub-scores than the control group by CAMCOG test.4.N-back tasks: before each condition, two seconds reminder show each load conditions in n-back (Repeat the current immediately: 0-back; Repeat the before one number: 1-back; Repeat the before two number: 2-back). Internal Group comparison indicate that in the normal group, the hyperthyroidism group and the adult SCH patients before treatment the accuracy rate decline as memory load increased. In normal bilateral interest areas (M/IFG, DLPFC, PreMA, SMA/ACC, and PA) we discover BOLD signal changes related to memory load, which showed the effects of load indicators can be used to analyze patient data. In the group of the SCH patients before treatment the BOLD signal which related to memory load appears only in the bilateral PreMA and bilateral parietal lobe, which is not found in other areas of interest (DLPFC, M/IFG, SMA/ACC; GLM) .5.Therapeutic efficacy: After 6 months' treatment, SCH children patients showed no difference in plasma FT3, FT4 level compared with the control.(1)The children SCH patients' scores of classification, comprehend, coding, knowledge, mapping, speech total scores and the entire total score improvement was significantly better than placebo group,, replacement therapy group' scores of operating scale and understanding are still lower than the normal group.(2).the adult SCH patients exhibited the same accuracy rate as the euthyroid subjects in N-back task. SCH patiens have shown a normal trend in the five regions of interest.(3) elderly SCH patients with TSH>10 mIU/ L has significantly increased in total scores, memory, thinking and language scores by CAMCOG test. The patiens with TSH<10 mIU/ L has improved significantly superior to placebo treatment in total scores, memory and thinking scores by CAMCOG test scores in the L-thyroxine group is close to the normal control group. Conclusions: The children with SCH have broader scope of damage in cognitive impairment, which have significantly improved especially the language ability after replacement therapy. After proper treatment, SCH patients's corresponding neural basis of working memory capacity can be restored. The elderly patients with SCH have mild cognitive impairment.These findings suggested that cognitive impairment is often seen symptoms in thyroid hormone diseases, the frontal cortext is the main neural network involved in the cognitive disoders in SCH patients. The early thyroid hormone replacement therapy improves the cognitive function and the life quality in patients with thyroid hormone diseases.