Thyroid disfunction and cognitive deficits research paper
Running head: THYROID DYSFUNCTION AND COGNITIVE DEFICITS IN THE ELDERLY1 Thyroid Dysfunction and Cognitive Deficits in the Elderly Tiffany Sinclair Columbia College November 28, 2011
THYROID DYSFUNCTION 2 Abstract The intention of this paper is to highlight the cognitive deficits associated with thyroidfunction in the elderly. Thyroid function research has found connections to cognitive deficitsconcerning memory impairment, depression, dementia, Alzheimer’s disease, and mood inconnection with even subclinical levels of thyroid hormone imbalance in the elderly affected.The aging population appears to be impacted negatively at an even greater rate than the youngerpopulation, and left untreated may suffer detrimental deficits including dementia. Medicationtherapies concerning thyroid disorders have proven effective in counteracting deficits and mayalso show with increased research, promise in slowing or preventing the onset of dementia in theelderly population. A review of research on thyroid function will look to validate if and howcognitive function is impaired by thyroid dysfunction, and if treatment can reverse cognitive andmood deficits found in patients affected at subclinical and clinical levels.
THYROID DYSFUNCTION 3 Thyroid Dysfunction and Cognitive Deficits in the Elderly Extensive research in the medical field has evaluated the impact of thyroid dysfunctionon cognition. The psychology field does not appear to have the expansive research warrantedgiven many of the findings in recent medical studies. Cognitive psychology may benefit fromfurther studies that focus on thyroid hormone (TSH) regulation in the body and the cognitive andmood deficits patients may experience when left untreated. Diagnostics, treatment, and therapyof affected patients may be compromised if a thyroid imbalance is left undetected, andparticularly in the elderly, may have detrimental effects to health and cognitive function.Several studies have been reviewed to assess the value of thyroid hormones in cognitivefunctioning and mood. The findings indicate that deficits may be found on both spectrums ofthyroid disorder, hyperthyroid and hypothyroid. Detection and treatment are vital to theprevention and improvement of deficits in cognition and mood experienced, and may serve as aninvaluable resource in the study of dementia and Alzheimer’s. To understand the importance of thyroid function in cognition, an understanding ofthyroid hormones should first be examined. The thyroid regulating hormone or thyrotropin(TSH) is secreted by the pituitary gland while 2 other thyroid hormones are produced andmetabolized using iodine and selenium from the body; free thyroxine (FT4), and freetriiodothyronine (FT3) (Triggiani, et al., 2009). Together these elements allow the thyroid glandto perform functions of “metabolism, growth, physiological processes, and reproductivefunction” (Triggiani, et al., 2009). When factors and functions required to produce necessarysynthesis of these hormones are imbalanced, such as an increase or decrease in iodine orselenium intake, or improper thyroid development or growth occurs, thyroid dysfunction mayresult. When the thyroid does not function properly or hormones levels are improperly
THYROID DYSFUNCTION 4distributed, studies have found cognitive and mood impairments in affected subjects compared tocontrol groups. Considering the impact of iodine on proper thyroid function, the first study examined willbe the Invecchiare in Chianti study. This cross sectional study took place in the Italian town ofChianti with almost 1200 volunteer participants ranging in age from 23-102, and categorizingparticipants in groups of young and old as well as by severity of thyroid dysfunction (Ceresini, etal., 2009). Those with dementia were excluded. Thyroid plasma concentration levels of TSH,FT3, and FT4 were measured in participants, as well administering the Mini Mental State Exam(MMSE) and adjusting for confounders. Subclinical thyroid dysfunction was found to be moreprevalent among the older population, with hyperthyroidism more prevalent thanhypothyroidism, which is the data of focus (Ceresini, et al., 2009). The research revealed agecorrelates with hormones TSH and FT3 decreasing as age increases, while FT4 increased withage. The subclinical hyperthyroid group scored lower on the MMSE than healthy controls, andsuffered more cognitive deficits. The study took place in an iodine deficient geographicallocation; there is a possibility of iodine concentrations being related to the outcome of anincreased subclinical hyperthyroid older population (Ceresini, et al., 2009). The Chianti study provides interesting data proposing geographical influence in thyroidfunction due to iodine concentration. The study concluded that “subclinical hypothyroidism wasthe most prevalent thyroid disorder in Italian elderly and is associated with cognitive deficits”(Ceresini, et al., 2009). While assessing a large sample and providing insight into age andseverity of thyroid dysfunction categorically, did not however utilize an array of cognitivefocused tests to provide evidence of particular function deficits and mood. It is important to notehowever cognitive deficits were found in even subclinical hyperthyroid affected subjects,
THYROID DYSFUNCTION 5showing overt dysfunction is not necessary for deficits to arise. The prevalence among the olderpopulation confirms findings in other studies who have found this population to be increasinglyaffected by thyroid disorders as age increases. The second study examined sought to determine if other impacts accompanied by agingcould explain the cognitive deficits found in elderly with thyroid dysfunction. The sample of 82normal TSH and 15 untreated hypothyroid community elderly subjects volunteered and were allhighly educated (Cook, et al., 2002). This study assessed memory impairment in the elderlyassociated with elevated TSH with MRI, cognitive, and depression testing as well asanticholinergic medication serum measurements including: The MMSE, Rey Auditory VerbalLearning Test, two measures from the Welscher’s Adult Intelligence Scale-III - The DigitSymbol Coding Test and backward digital scan, blood TSH levels, geriatric depression scale,two conditions using the verbal application of the N back test, White Matter Hyperintensiy(WMH) and FLAIR image atrophy ratings determined by two individual neuroradiologists wereall used to represent and analyze the data (Cook, et al., 2002). Normal and high TSH groupswere compared using the testing data with multivariate analysis of variance, and ANCOVASwere used to rule out MMSE scores as a result of cognitive impairments showing in the highTSH group (Cook, et al., 2002). The MRI and WMH results were compared to assess cardiovascular co-morbidpossibilities, and the geriatric depression scale was compared between groups to assess for co-morbid depression. Findings indicated the high TSH group performed poorly on the MMSE andverbal recall compared to the normal TSH group. These deficits may be overcome with hormonereplacement therapy which may be a consideration for those elderly with even mild elevations ofTSH. Subjects showing signs or symptoms of dementia were ruled out, however detection is
THYROID DYSFUNCTION 6complex, and difficult to diagnose in the early stages (Cook, et al., 2002). The sample wasnarrow due to the use of a community of highly educated elderly which may not represent theglobal elderly population. The findings are significant given the wide array of testing to addressco-morbid possibilities however, and warrant further investigation into the treatment practices ofelderly patients showing even slight elevations of TSH. Treatment may be crucial in the reversal of cognitive and mood deficits associated withelevated THS levels. A study seeking to verify reversal of cognitive deficits in affected subjectswith increased thyroid hormone levels to the brain, found that levothyroxine (L-T4) treatmentmay be effective in correcting mood and cognitive deficits in those with elevated TSH (Miller, etal., 2006). With a control group of 14 and an untreated hypothyroid group of 10, verified byelevated basil TSH levels, the 3 month study examined subjects of both sexes between the agesof 18-55 pre and post treatment to verify difference. Prior to acceptance into the study, sampleswere given medical, physical, neuropsychiatric, and neuropsychological screening. Independentt test pre treatment, ANOVAS, Two-Tailed, hierarchical multiple regressions, and a HAM-Dscoring tests were applied to stages of the data to determine significance (Miller, et al., 2006). The study revealed that the hypothyroid group post treatment with L-T4, had reducedHAM-D depression scores and specific memory retrieval deficits, and increased short and longdelayed recall as well as improved mood. These results showed little change in the controlgroup, with the hypothyroid group ending in similar scores to the control group post treatment.The researchers of this study also concluded that treatment and detection may be vital to theprevention and further deficits that may accompany thyroid dysfunction associated withhypothyroid and dementia with severe cases (Miller, et al., 2006). Untreated hypothyroid whichwith severity may cause or increase the onset and deficits found in dementia, are an important
THYROID DYSFUNCTION 7indication in this study that agrees with previous work by other research with the elderly andthyroid dysfunction. Although the sample was small in this study, the testing measures mayprove to be a valuable contribution to future studies examining relationships between thyroid anddementia for treatment outcomes. “Cognitive deficits simulating dementia can be caused bythyroid dysfunction” (Mafrica & Fodale, 2008), and evidence found supporting thyroidhormones relationship with the cholinergic system know to be impaired early on in thosesuffering from Alzheimer’s disease (Mafrica & Fodale, 2008), suggests data from these studiesmay be invaluable in determining early detection, origin, and treatment significance in long termgoals of prevention. An interesting implication that surgery may cause or influence thyroid dysfunction alsosought to determine correlates of thyroid hormone imbalance to Alzheimer’s disease anddementia. Euthroid sick syndrome (ESS) found in post operative patients, possibly caused bypsycho-physical stress, showed that reductions in T3 and T4 serum absent of increased TSHoccurred hours after major surgery, and in the elderly results in cognitive deficits which arereversible (Mafrica & Fodale, 2008). Also important may be the early showing of negativelyregulated amyloid- β protein (AβPP) found in Alzheimer’s disease, which negative regulation ofthe protein is also caused by imbalanced thyroid hormones; further suggesting the association ofthyroid hormones relating to the cholinergic system (Mafrica & Fodale, 2008). Thyroiddysfunction impairs cognitive abilities including “attention, motor speed, memory, and visual-spatial organization, even more so in the elderly with hypothyroidism, while hyperthyroid anddepression also cause significant cognitive impairment as well (Mafrica & Fodale, 2008).Treatment of hormone replacement has been found to reverse and normalize these deficits(Mafrica & Fodale, 2008).
THYROID DYSFUNCTION 8 An older study also researched the effect of hypothyroid on timing, activity, and speedutilizing basic physical tests to track changes with hormone replacement treatment forcomparison with a previous study using a hyperthyroid test group. Test of keyboard tapping,auditory and visual reaction time, estimation of time, and leg lift persists were used indetermining the cognitive deficits and improvements of thyroid groups compared to a controlgroup pre and post treatment in terms of arousal-performance (Stern, 1959). Both groups used32 subjects of both sexes with the hypothyroid group coming from an outpatient endocrinologyclinic with diagnosed hypothyroidism with an age range of 22-67 with retest occurring after 6months of treatment. While perhaps basic in methodology, the tests revealed that three of thesetests; tapping, audio, and visual reaction time, showed significant improvements from pre-testmeasures, in the direction of the control group results. Tapping speed decreased with treatmentwhich was increased prior compared to the control group, and time estimation and leg liftpersists showed little change in either study between groups, even thought time estimation resultsdiffered significantly in hypo and hyperthyroid groups compared to the normal controls (Stern,1959). The researcher concluded that the differences observed were due to arousal behavior,which is described from slow to excited, with hypo at the low end, normal in the middle andhyper at the high end (Stern, 1959). Similar associations to arousal were made in studies usingrats around the same time frame using motivation to discuss results. The study using threegroups to track and determine extinction, motivation, and rates of acquisition applied a modifiedSkinners box with a bar to press for food as reward incentive to create operant response. Thestudy used a hypothyroid group by inducing hypothyroidism using thiouracil, and a hyperthyroidgroup induced with thyroxine, and a control group injected with saline (Denenberg & Meyers,
THYROID DYSFUNCTION 9Learning and hormone activity: I. Effects of thyroid levels upon the acquisition and extinction ofan operant response., 1958). Treatment was administered in three forms: Post weaning, uponadulthood, or upon mastery of the operant response for each category and tested for motivationusing the learned operant response (Denenberg & Meyers, Learning and hormone activity: I.Effects of thyroid levels upon the acquisition and extinction of an operant response., 1958). Similar to the study above defining results in terms of arousal, this study using rats alsofound significant correlations to differences in motivation representing the findings. Nodifferences were observed in extinction or acquisition rate between groups with analysis ofvariance, however rate of response showed lower rates for the hypothyroid group and higher forhyperthyroid group (Denenberg & Meyers, Learning and hormone activity: I. Effects of thyroidlevels upon the acquisition and extinction of an operant response., 1958). The same authors thenperformed another study to test thyroid dysfunction in rats on learned operant response retentionusing starvation as motivation again with the modified Skinners box and bar press for dispensingfood (Denenberg & Meyers, Learning and hormone activity: II. Effects of thyroid levels uponretention of an operant response and upon performance under starvation.). The hypothesis wasthat the thyroid altered rat groups would experience retention impact. Utilizing the samemethods as above to induce hypo and hyperthyroid states, 5 groups were tested: Staved control,starved thiouracel, thyroxine, thiouracil, and control with saline groups (Denenberg & Meyers,Learning and hormone activity: II. Effects of thyroid levels upon retention of an operantresponse and upon performance under starvation.). The findings indicated significant lower mean responses by the thiouracel groups, withnon-starved and starved both performing similarly. This indicated these groups had similarmotivational peaks unassociated with hunger drive in comparison to the other groups. The
THYROID DYSFUNCTION10authors concluded that thyroid impairment impacted motivation, however did not impact operantrecall (Denenberg & Meyers, Learning and hormone activity: II. Effects of thyroid levels uponretention of an operant response and upon performance under starvation.). Advancedtechnologies developed since these studies such as neuroimaging may prove useful in adaptationmodels using similar techniques to induce hypo and hyper thyroid states for study in animals. Todetermine brain reactions and changes with thyroid dysfunction over ages and in conjunctionwith dementia and Alzheimer’s findings for comparison, may prove valuable for researchregarding the elderly response to thyroid dysfunction and the cognitive deficits associated.Updated techniques and technology may help to validate or determine the findings in outdatedresearch, which applied to diseases in the elderly such as dementia and Alzheimer’s may allowfor renewed understanding and new or improved results lending to cognitive ability impacts andorigins associated with thyroid dysfunction. Thyroid dysfunction not only impacts cognitive functions, but also emotion (Bauer,Goetz, Glenn, & Whybrow, 2008). Hypothyroidism may impair “general intelligence,psychomotor speed, visual-spatial skills and memory” unattributed to attention deficit, butcaused by specific retrieval deficits (Bauer, Goetz, Glenn, & Whybrow, 2008), whichspecificities have also been indicated and highlighted in studies throughout this paper. Thyroidmetabolism in the adult brain being disrupted can also lead to two common causes of thyroiddysfunction: Autoimmune disorders such as Graves disease result in hyperthyroidism andHashimototo’s thyroiditis result in hypothyroidism. In addition to impairing mood andintellectual performance, severe forms of hypothyroidism can result in severe depression andeven “mimic dementia” which may result in irreversible dementia when left untreated (Bauer,Goetz, Glenn, & Whybrow, 2008). Less severe forms affecting patients with treatment will
THYROID DYSFUNCTION11likely recover normal cognitive function upon return to euthyroid status (Bauer, Goetz, Glenn, &Whybrow, 2008). Discussion While researching data concerning cognitive deficits associated with thyroid dysfunction,there was an apparent gap in reference material in the psychology database compared to themedical database. Given the important and relevant data provided in the medical research on thistopic, it is clear that the field of psychology is lagging in research crucial to diagnostic, etiology,and treatment data necessary for incorporation. The psychology field exposed to patients withpossible symptoms of thyroid dysfunction may miss-diagnose or delay vital treatment id thyroiddysfunction remains undetected, particularly in the elderly population exhibiting early signs ofdementia. Many of the studies utilized extensive testing to determine findings, which may behelpful if data is cross referenced to determine best testing outcomes and measures specificallyfor thyroid hormone related studies. Further research should extend the studies in length toaccommodate proper treatment satisfaction to euthyroid levels before or in addition to posttesting as full achievement of normal thyroid levels may take up to two years to acquire.Important to note in researching thyroid dysfunction and cognitive defects, is a lack of data onpatients having complete thyroidectomies, or removal of the thyroid gland. Studies may benefitfrom researching this category of patients with the ability to track average time for full return toeuthyroid status and deficits encountered pre and post surgery. Conclusion The studies performed allow for considerable opportunities to further past research usingimproved technology and updated knowledge of thyroid dysfunction, and may give insight into
THYROID DYSFUNCTION12complex and irreversible diseases consuming so many resources for answers. Ultimately thefields of neuroscience and psychology may provide much needed insight into thyroid metabolismand cognitive deficits resulting from dysfunction by combining recourses and research focusedon the etiology of dementia and Alzheimer’s from the perspective of thyroid hormone impacts.There is little doubt given the findings among these studies that thyroid hormones have acognitive, physical, and emotional impact in the negative direction when imbalanced, and furtherinvestment in research among age groups and severity is warranted and perhaps even holds thekey too many solutions affecting our elderly population.
THYROID DYSFUNCTION13 ReferencesBauer, M., Goetz, T., Glenn, T., & Whybrow, P. (2008). The thyroid-brain interaction in thyroid disorders and mood disorders. Journal Of Neuroendocrinology , 20 (10), 1101-1114.Ceresini, G., Lauretani, F., Maggio, M., Ceda, G. P., Morganti, S., Usberti, E., et al. (2009). Thyroid function abnormalities and cognitive impairment in elderly people: Results of the invecchiare in chianti study. Journal of the American Geriatrics Society , 57 (1), 89- 93, 5p, 3 charts. doi: 10.1111/j.1532-5415.2008.02080.xCook, S. E., Nebes, R. D., Halligan, E. M., Burmeister, L. A., Saxton, J. A., Ganguli, M., et al. (2002). Memory Impairment in elderly individuals with a mildly elevated serum TSH: The role of processing resources, depression and cerebrovascular disease. Aging, Neuropsychology & Cognition , 9 (3), 175, 9p.Denenberg, V. H., & Meyers, R. D. (1958). Learning and hormone activity: I. Effects of thyroid levels upon the acquisition and extinction of an operant response. Of Comparative And Physiological Psychology , 51 (2), 213-219. doi: 10.1037/h0046929Denenberg, V. H., & Meyers, R. D. Learning and hormone activity: II. Effects of thyroid levels upon retention of an operant response and upon performance under starvation. Journal Of Comparative And Physiological Psychology , 51 (3), 311-314. doi: 10.1037/h0045371Mafrica, F., & Fodale, V. (2008). Thyroid function, Alzheimers disease and postoperative cognitive dysfunction: a tale of dangerous liaisons?. Journal Of Alzheimers Disease: JAD , 14 (1), 95-105.Miller, K. J., Parsons, T. D., Whybrow, P. C., van Herle, K., Rasgon, N., van Herle, A., et al. (2006). Memory improvement with treatment of hypothyroidism. International Journal of Neuroscience , 116 (8), 895-906, 12p. doi:10.1080/00207450600550154.Stern, M. H. (1959). Thyroid function and activity, speed, and timing of behaviour aspects.
THYROID DYSFUNCTION14 Canadian Journal of Experimental Psychology/Revue Canadienne De Psychologie , 13 (1), 43-48.Triggiani, V., Tafaro, E., Giagulli, V., Sabbà, C., Resta, F., Licchelli, B., et al. (2009). Role of iodine, selenium and other micronutrients in thyroid function and disorders. Endocrine, Metabolic & Immune Disorders Drug Targets , 9 (3), 277-94.