|Year : 2013 | Volume
| Issue : 1 | Page : 15-19
Chronoscopic reading in whole body reaction times can be a tool in detecting cognitive dysfunction in hypothyroidism: A case-control study
Vitthal Khode1, Shambhulingaiah1, Umesh Rajoor2, Santosh Ramdurg3, Komal Ruikar1
1 Department of Physiology, SDM College of Medical Sciences, Sattur, Dharwad, Karnataka, India
2 Department of General Medicine, SDM College of Medical Sciences, Sattur, Dharwad, Karnataka, India
3 Department of Psychiatry, SDM College of Medical Sciences, Sattur, Dharwad, Karnataka, India
|Date of Web Publication||10-Jan-2013|
Department of Physiology, SDM College of Medical Sciences, Sattur, Dharwad, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Hypothyroidism investigated as a risk factor for cognitive decline. It is known that difference between simple and choice reaction time (RT) implies time required for cognition. Though delayed RTs indicate involvement of cognition, they cannot quantify how much time is required for cognition. In whole body choice reaction time (WBCRT), RT is split into two chronoscopic readings, Chronoscope-1 (C1) and Chronoscope-2 (C2). C1 measures time required for central processing, which requires cognition and C2 measures total RT. C2-C1 measures time required for the peripheral motor response. We hypothesized that WBCRT C1will be delayed in hypothyroidism, and WBCRT C1 will have predictive value in detecting cognitive dysfunction. Settings and Design: Hospital based case control study. Materials and Methods: Study was conducted on 99 subjects using visual and whole body reaction timers having criteria of age (20-60years) and hypothyroidism, compared with an equal number of age and sex matched controls. Statistical analysis was done by Independent t-test and duration of hypothyroidism was correlated with cognition times (WBCRT C1) using Pearson's correlation. Predictive value of WBCRTC1 was calculated by using receiver operating characteristic curve. Results: Delayed visual simple reaction time (VSRT), Visual choice reaction time (VCRT), Whole body simple reaction time (WBSRT), and WBCRT observed among subjects of hypothyroidism when compared with controls. Choice RTs were more delayed compared to simple RTs. WBCRT C1 (578±110 ms) was more delayed than WBSRT C1 (396 ± 87.1 ms) among hypothyroid patients indicating cognitive dysfunction. There was no significant correlation between duration of hypothyroidism with cognition. The best cut-off value for WBCRTC1, when predicting cognitive dysfunction in hypothyroidism was 527 ms. (sensitivity 48% specificity 40.8%). Conclusions: WBCRT C1 can be used as a tool to detect cognitive dysfunction.
Keywords: c0 ognition, hypothyroidism, reaction times
|How to cite this article:|
Khode V, Shambhulingaiah, Rajoor U, Ramdurg S, Ruikar K. Chronoscopic reading in whole body reaction times can be a tool in detecting cognitive dysfunction in hypothyroidism: A case-control study. Thyroid Res Pract 2013;10:15-9
|How to cite this URL:|
Khode V, Shambhulingaiah, Rajoor U, Ramdurg S, Ruikar K. Chronoscopic reading in whole body reaction times can be a tool in detecting cognitive dysfunction in hypothyroidism: A case-control study. Thyroid Res Pract [serial online] 2013 [cited 2021 Oct 28];10:15-9. Available from: https://www.thetrp.net/text.asp?2013/10/1/15/105841
| Introduction|| |
Thyroid hormone plays a critical role in adult brain, influencing both mood and cognition. , It is well accepted that hypothyroidism is related to pathological alterations of thyroid hormone distributions, and functioning in both hippocampus and cerebral cortex. ,, There are various adverse effects of hypothyroidism on cerebral-dependent neurocognitive functions ,,,, including working memory, , which are the executive and attentional control of short-term memory providing for temporal storage and online manipulation of information. 
Reaction time (RT) is time taken from the onset of stimulus to an appropriate response which includes, rate of processing of sensory stimuli by central nervous system and its execution by motor response. It is known that difference between simple and choice RT implies cognition. , Investigators have shown cognition is delayed in hypothyroidism. Although delayed RTs indicate involvement of cognition, they cannot quantify how much time is required for cognition.
In whole body choice reaction time (WBCRT), RT is split into two chronoscopic readings, whole body choice reaction time Chronoscope-1(WBCRTC1) and whole body choice reaction time Chronoscope-2(WBCRTC2). WBCRTC1 is time required from visual stimuli to subject lifts his leg from starting platform, which measures time required for central processing or cognition. WBCRTC2 is time required from visual stimuli to end task. WBCRTC2-C1 is time required for the peripheral response. The purpose of this study is whether reaction times particularly WBCRTC1 can be a measure of cognitive dysfunction in hypothyroidism. The hypothesis of the present study was that WBCRTC1 in hypothyroidism without overt cerebrovascular disease would be delayed. We determined visual reaction and whole body RTs both simple and choice, so cognitive performance in hypothyroidism and in controls without cerebrovascular disease, target organ damage, or other vascular risk factors. We tried to find the predictive value of WBCRTC1 in detecting cognitive dysfunction in them.
| Materials and Methods|| |
After getting approval of the Ethical clearance committee of the institution, this cross-sectional case-control study was carried out over 6months (August 2010 to January 2011), with purposive sample with the criteria of age and hypothyroidism. The selection of sample was carried out from the outpatient department of medicine of our institution and 99 individuals participated in the study. Whole population was divided into two groups. Group 1 consisted randomly selected clinically diagnosed hypothyroid patients more than 2 years of duration aged between 20 and 60 years. Group 2 consisted randomly selected sex, and age matched controls from the college staff and subjects attending medical out patient department (OPD) for a routine checkup. Sample size was determined by standard error obtained by pilot study. Every individual was briefed about the study before; its importance, and procedural details and written consent of participants were taken before recording the various RTs. Following subjects were excluded from the study: diabetics, hypertensives, smokers, retinopathy, motor neuron diseases, cardiovascular, cerebrovascular disorders, neuropathy, and chronic renal disorders. We also excluded patients having chronic lower-back pain or spasms, deformities of the spine, bones or joints (including advanced arthritis), spinal cord injuries, or other damage to the nervous system, non-healing skin ulcers, current drug or alcohol dependence. Individuals taking any prescription medicine to prevent dizziness were also excluded.
Blood samples were collected on the morning after a 12h fast. Aliquots of serum and plasma were obtained within 3h and stored at−80C. Plasma concentrations of Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured using a chemiluminescent immunoassay. The reference normal ranges were 0.53-5.6 IU/ml for TSH, 1.4-4.2 pg/ml for FT3, and 0.8-2ng/l for FT4. TSH was performed in all hypothyroid and controls. FT3 and FT4 were performed only in 25 hypothyroid patients. The basic parameters and detailed history were recorded. General checkup of Pulse, blood pressure, height, weight, food habits, exercise patterns were recorded. Ophthalmic evaluation was done by using snellen and jeagers chart.
Equipment used for reaction timers:
The reaction timers:
- Visual reaction time
Whole body reaction time
- Visual simple reaction time (VSRT)
- Visual choice reaction time (VCRT)
- Whole body simple reaction time (WBSRT) (Chronoscope-1, Chronoscope-2 and Chronoscope 2-1)
- Whole body choice reaction time (WBCRT) (Chronoscope-1, Chronoscope-2 and Chronoscope 2-1)
Anand Agencies, Pune manufacturer of research tool RT apparatus, with chronoscope compartment showing time in milliseconds.
Procedure: After brief instructions, three trials for each of VSRT, VCRT, WBSRT and WBCRT were given and the individual RT in milliseconds was recorded 5times in both hypothyroid patients and controls. An attempt was made to obtain at least five acceptable recordings for each participant. Measurements of the VSRT, VCRT and WBSRT were considered reproducible, if the difference between maximum and minimum values did not exceed 50 ms. Reliability of the test was calculated based upon the data obtained in pilot study. Coefficient of correlation for VSRT was 0.927 with α error 0.9844. VSRT-The subject is instructed to press the right button as soon as red-light glows and chronoscope reading is recorded. VCRT-The subject is instructed to press left button when green-light glows and right button when red-light glows and RT are recorded. WBSRT-The subject standing on the starting board is instructed to watch the glowing arrow and to step one leg on the stepping board in that single direction. C1, gives time taken for lifting of the foot from the onset of the stimulus whereas C2, gives the total time required for placing the foot on the stepping board from the onset of stimulus, and C2-C1 gives the movement time from starting board to stepping board, which is the time taken for motor activity. WBCRT-The subject is asked to move either of the legs according to the direction to a glowing arrow either to right, front, left, behind, and right again, which involves more cognition compared to WBSRT, Chronoscopic reading-1, Chronoscopic reading-2 and C2-C1 mean same as that of WBSRT.
The results were tabulated separately, and statistical results are presented as mean ±SD. The software analyzer used was SPSS version 16. The data were analyzed by independent t-test, which indicates the level of difference between groups, with significance at 5% level using t-Stat. i.e., P values <0.05. Pearson's correlation was performed to find the correlation between duration of hypothyroidism, TSH, and C1WBCRT. To determine the accuracy and respective best cut-off values of C1WBCRT for predicting cognitive dysfunction, and TSH predicting hypothyroidism, the receiver operating characteristic (ROC) curves and their corresponding areas below the curve (AUC) were used. A P value of <0.05 was considered statistically significant.
| Results|| |
According to literature, the independent variables such as age, sex, body mass index (BMI), physical fitness, influence RT. As per the [Table 1], there is no significant difference among the age. The mean age of controls was 40.2 years, and hypothyroidism was 40.4 years. There were three males in Group 1, and four males in Group 2. Rests of the subjects were females. [Table 1] also shows, mean of measured values of random blood sugar (RBS), systolic blood pressure (SBP), diastolic blood pressure (DBP). There was no significant difference in these parameters as per [Table 1]. There was significant difference in TSH levels in hypothyroid patients compared to controls.
In significant delayed VSRT, VCRT were observed in hypothyroidism compared to controls with P values 0.481, 0.309 respectively. Choice RTs were more delayed. WBSRTC1, WBSRTC2, and WBSRTC2-C1 were delayed in hypothyroidism compared to controls and were statistically insignificant (P 0.485, 0.477, 0.737 respectively). [Table 2] WBCRTC1, WBCRTC2, and WBCRT C2-C1 were delayed in hypothyroidism compared to controls and were statistically significant (P 0.011, 0.000, 0.0005 respectively). Choice RTs were more delayed than simple RTs. WBCRTC1 was more delayed compared to WBSRTC1. There was no significant correlation between duration of hypothyroidism (average 2.89 years) with and WBCRTC1. There was significant correlation between TSH and WBCRTC1. (r = 0.301 P = 0.002) ROC curve of WBCRTC1 when predicting cognitive dysfunction in a hypothyroid patient was constructed and the AUC was found to be 0.326 (95% CI, LB 0.220 UB 0.431) statistically significant (P = 0.003). The best cut-off value of WBCRTC1, when predicting cognitive dysfunction in a hypothyroid patient was 527 ms (sensitivity 48%; specificity 40.8%). ROC curve of TSH when predicting hypothyroidism was constructed and the AUC was found to be 0.289 (95% CI, LB 0.180 UB 0.397) statistically significant (P = 0.000). The best cut-off value of TSH, when predicting hypothyroidism was 3.24 Iu/ml. (sensitivity 44%; specificity 34.7%).
| Discussion|| |
We observed that RTs are delayed in hypothyroidism. Chronoscopic reading 1 in WBCRT was significantly delayed in hypothyroidism, which indicates involvement of cognition. We found WBRTC1 can be predictive of cognitive dysfunction in hypothyroidism.
Mental activities involved in the acquisition, storage, retrieval, and use of information are referred to here by the term cognition.  An increased risk of declining cognitive function with aging is well-known, especially with regard to working memory, information processing speed, and long-term memory. ,,, Information processing speed is an important resource, defined by the time parameters of a specific cognitive task. Shortest latencies are usually associated with youth and better performances. The label "cognitive slowing" has been applied to increases in those latencies, which in turn can be held responsible for many aspects of declining cognitive functioning. Epidemiological studies that have investigated the relationship between subclinical hypothyroidism , or subclinical hyperthyroidism , and impaired cognition had reported inconsistent findings.
Cognitive domains include attention and concentration, language, memory, psychomotor function, and executive function. There are validated neurocognitive tests to measure these domains, mapped to critical brain regions by lesional studies and functional imaging. RT is a reliable tool to measure attention, concentration, execution and psychomotor speed. RT measurement includes the latency in the sensory neural code traversing peripheral and central pathways; perceptive, cognitive, volitional processing. In choice RT, time required for central processing increases where as time required for the peripheral response does not alter much. At this point, we require a tool which clearly measures the time required for central processing and peripheral processing in total RT. Many studies have shown the delay in visual and auditory simple and choice RTs in cognitive dysfunction,  but they have failed to explain whether the delay was because of central processing or time taken for the peripheral response. In our study along with visual simple and choice RTs we have measured whole body simple and choice RT in which WBRTC1 apparently measures the time required for cognition, the time taken for lifting the foot from the onset of stimulus from starting board. WBRTC2 measures apparently motor signal traversing both central and peripheral neuronal structures, the total time required for placing the foot on stepping board from the onset of stimulus. Therefore, it becomes easy to tease out central effect verses peripheral effects when RTs are slowed. Our focus on the study was to measure WBCRTC1 in hypothyroidism and compare with controls, which approximately tell the difference in cognition between these two groups. We hypothesized that measurement of WBCRTC1 can be used as screening tool to detect cognitive dysfunction.
In the present study, visual RTs are delayed in hypothyroidism. Choice RTs were more delayed indicates cognition is affected. Both WBCRTC1 and WBCRTC2 were delayed in hypothyroidism, which indicates there is involvement of both central processing, i.e., cognition and peripheral response. WBCRTC1 was more delayed than WBSRTC1 in hypothyroidism, which again indicates cognition is involved.
Whole body RTs were delayed more in hypothyroidism compared to visual RTs. Therefore, we can say whole body RT measurement is more sensitive. This could be due to different representational areas, which are supplied by different vessels. Anterior central artery supplies the area representing hand (visual auditory RTs) and posterior central artery supplies the area representing legs (whole body RT). There was no significant correlation between duration of hypothyroidism and WBCRTC1 (P = 0.0109). The reason could be all patients were on medication for treatment of hypothyroidism. The sensitivity and specificity of WBCRTC1 detecting cognitive dysfunction was 48% and 40.8% respectively. We need large sample size to improve sensitivity and specificity.
One fallacy about our study was, we did not perform the gold standard tests, which can identify cognitive dysfunction so that we can compare our findings and assess sensitivity and specificity of the test. These batteries of tests are considered gold standard as they evaluate multiple aspects of cognition. However, batteries of tests are time-consuming and requires skilled staff. On the contrary, RTs can be easily performed on OPD basis. They can be sensitive indicators of cognitive dysfunction and peripheral response which are altered in peripheral neuropathy. So our strength of study is we can use RTs as screening tool for early detection of cognitive dysfunction. There are no systemic reviews implicating RTs, especially WBCRTC1, can detect cognitive dysfunction. WBCRTC1 can apparently measure time required for cognition if not accurately. This study may provide a platform for further studies in this direction, particularly underlying mechanisms.
From this study, we can conclude that hypothyroidism does affect RT, severity of slowing may be related to difficulty with the task and prevalence of central and peripheral nerve deficits seen as side effects of hypothyroidism. Auditory, visual RTs the simplest of tasks with the shortest path between peripheral and central nervous system showed less delayed RTs. Choice visual RTs will be more delayed because of involvement of complicated circuits. When a more complicated task, including detecting movement, signal transmission and interpretation is given as in whole body RTs, significant difference in RTs will be observed. With WBCRT, RT the difference increases. This difference is attributed by cognition. In whole body RT with chronoscopic reading C1 and C2-C1 probably it is possible to measure how much of time is required for central processing and how much of time is required for motor response.
| References|| |
|1.||Bauer M, Goetz T, Glenn T, Whybrow PC. The thyroid-brain interaction in thyroid disorders and mood disorders. J Neuroendocrinol 2008;20:1101-14. |
|2.||Davis JD, Tremont G. Neuropsychiatric aspects of hypothyroidism and treatment reversibility. Minerva Endocrinol 2007;32:49-65. |
|3.||Constantinou C, Margarity M, Valcana T. Region-specific effects of hypothyroidism on the relative expression of thyroid hormone receptors in adult rat brain. Mol Cell Biochem 2005;278:93-100. |
|4.||Broedel O, Eravci M, Fuxius S, Smolarz T, Jeitner A, Grau H, et al. Effects of hyper-and hypothyroidism on thyroid hormone concentrations in regions of the rat brain. Am J Physiol Endocrinol Metab 2003;285:E470-80. |
|5.||Dugbartey AT. Neurocognitive aspects of hypothyroidism. Arch Intern Med 1998;158:1413-8. |
|6.||Lass P, Slawek J, Derejko M, Rubello D. Neurological and psychiatric disorders in thyroid dysfunctions. The role of nuclear medicine: SPECT and PET imaging. Minerva Endocrinol 2008;33:75-84. |
|7.||Samuels MH. Cognitive function in untreated hypothyroidism and hyperthyroidism. Curr Opin Endocrinol Diabetes Obes 2008;15:429-33. |
|8.||Bunevicius R, Prange AJ. Mental improvement after replacement therapy with thyroxine plus triiodothyronine: Relationship to cause of hypothyroidism. Int J Neuropsychopharmacol 2000;3:167-74. |
|9.||Samuels MH, Schuff KG, Carlson NE, Carello P, Janowsky JS. Health status, mood, and cognition in experimentally induced subclinical hypothyroidism. J Clin Endocrinol Metab 2007;92:2545-51. |
|10.||Baddeley A. Working memory. Science 1992;255:556-9. |
|11.||Chiaravalloti ND, Christodoulou C, Demaree HA, DeLuca J. Differentiating simple versus complex processing speed: Influence on new learning and memory performance. J Clin Exp Neuropsychol 2003;25:489-501. |
|12.||Steinmetz J, Rasmussen LS, ISPOCD GROUP. Choice reaction time in patients with post-operative cognitive dysfunction. Acta Anaesthesiol Scand 2008;52:95-8. |
|13.||Smith JW, Evans AT, Costall B, Smythe JW. Thyroid hormones, brain function and cognition: A brief review. Neurosci Biobehav Rev 2002;26:45-60. |
|14.||Mariotti S, Franceschi C, Cossarizza A, Pinchera A. The aging thyroid. Endocr Rev 1995;16:686-715. |
|15.||Wahlin A, Bäckman L, Mäntylä T, Herlitz A, Viitanen M, Winblad B. Prior knowledge and face recognition in a community-based sample of healthy, very old adults. J Gerontol 1993;48:P54-61. |
|16.||Davis JD, Stern RA, Flashman LA. Cognitive and neuropsychiatric aspects of subclinical hypothyroidism: Significance in the elderly. Curr Psychiatry Rep 2003;5:384-90. |
|17.||Mariotti S, Barbesino G, Caturegli P, Bartalena L, Sansoni P, Fagnoni F, et al. Complex alteration of thyroid function in healthy centenarians. J Clin Endocrinol Metab 1993;77:1130-4. |
|18.||Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frölich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA 2004;292:2591-9. |
|19.||Jorde R, Waterloo K, Storhaug H, Nyrnes A, Sundsfjord J, Jenssen TG. Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment. J Clin Endocrinol Metab 2006;91:145-53. |
|20.||Roberts LM, Pattison H, Roalfe A, Franklyn J, Wilson S, Hobbs FD, et al. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med 2006;145:573-81. |
|21.||Kalmijn S, Mehta KM, Pols HA, Hofman A, Drexhage HA, Breteler MM. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study. Clin Endocrinol (Oxf) 2000;53:733-7. |
[Table 1], [Table 2]