1. Running head: THYROID DYSFUNCTION AND COGNITIVE DEFICITS IN THE ELDERLY
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Thyroid Dysfunction and Cognitive Deficits in the Elderly
Tiffany Sinclair
Columbia College
November 28, 2011

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Abstract
The intention of this paper is to highlight the cognitive deficits associated with thyroid
function in the elderly. Thyroid function research has found connections to cognitive deficits
concerning memory impairment, depression, dementia, Alzheimer’s disease, and mood in
connection 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 younger
population, and left untreated may suffer detrimental deficits including dementia. Medication
therapies concerning thyroid disorders have proven effective in counteracting deficits and may
also show with increased research, promise in slowing or preventing the onset of dementia in the
elderly population. A review of research on thyroid function will look to validate if and how
cognitive function is impaired by thyroid dysfunction, and if treatment can reverse cognitive and
mood deficits found in patients affected at subclinical and clinical levels.

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Thyroid Dysfunction and Cognitive Deficits in the Elderly
Extensive research in the medical field has evaluated the impact of thyroid dysfunction
on cognition. The psychology field does not appear to have the expansive research warranted
given many of the findings in recent medical studies. Cognitive psychology may benefit from
further studies that focus on thyroid hormone (TSH) regulation in the body and the cognitive and
mood deficits patients may experience when left untreated. Diagnostics, treatment, and therapy
of affected patients may be compromised if a thyroid imbalance is left undetected, and
particularly 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 cognitive
functioning and mood. The findings indicate that deficits may be found on both spectrums of
thyroid disorder, hyperthyroid and hypothyroid. Detection and treatment are vital to the
prevention and improvement of deficits in cognition and mood experienced, and may serve as an
invaluable resource in the study of dementia and Alzheimer’s.
To understand the importance of thyroid function in cognition, an understanding of
thyroid 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 and
metabolized using iodine and selenium from the body; free thyroxine (FT4), and free
triiodothyronine (FT3) (Triggiani, et al., 2009). Together these elements allow the thyroid gland
to perform functions of “metabolism, growth, physiological processes, and reproductive
function” (Triggiani, et al., 2009). When factors and functions required to produce necessary
synthesis of these hormones are imbalanced, such as an increase or decrease in iodine or
selenium intake, or improper thyroid development or growth occurs, thyroid dysfunction may
result. When the thyroid does not function properly or hormones levels are improperly

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distributed, studies have found cognitive and mood impairments in affected subjects compared to
control groups.
Considering the impact of iodine on proper thyroid function, the first study examined will
be the Invecchiare in Chianti study. This cross sectional study took place in the Italian town of
Chianti with almost 1200 volunteer participants ranging in age from 23-102, and categorizing
participants in groups of young and old as well as by severity of thyroid dysfunction (Ceresini, et
al., 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 more
prevalent among the older population, with hyperthyroidism more prevalent than
hypothyroidism, which is the data of focus (Ceresini, et al., 2009). The research revealed age
correlates with hormones TSH and FT3 decreasing as age increases, while FT4 increased with
age. The subclinical hyperthyroid group scored lower on the MMSE than healthy controls, and
suffered more cognitive deficits. The study took place in an iodine deficient geographical
location; there is a possibility of iodine concentrations being related to the outcome of an
increased subclinical hyperthyroid older population (Ceresini, et al., 2009).
The Chianti study provides interesting data proposing geographical influence in thyroid
function due to iodine concentration. The study concluded that “subclinical hypothyroidism was
the 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 and
severity of thyroid dysfunction categorically, did not however utilize an array of cognitive
focused tests to provide evidence of particular function deficits and mood. It is important to note
however cognitive deficits were found in even subclinical hyperthyroid affected subjects,

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showing overt dysfunction is not necessary for deficits to arise. The prevalence among the older
population confirms findings in other studies who have found this population to be increasingly
affected by thyroid disorders as age increases.
The second study examined sought to determine if other impacts accompanied by aging
could explain the cognitive deficits found in elderly with thyroid dysfunction. The sample of 82
normal TSH and 15 untreated hypothyroid community elderly subjects volunteered and were all
highly educated (Cook, et al., 2002). This study assessed memory impairment in the elderly
associated with elevated TSH with MRI, cognitive, and depression testing as well as
anticholinergic medication serum measurements including: The MMSE, Rey Auditory Verbal
Learning Test, two measures from the Welscher’s Adult Intelligence Scale-III - The Digit
Symbol 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 were
all used to represent and analyze the data (Cook, et al., 2002). Normal and high TSH groups
were compared using the testing data with multivariate analysis of variance, and ANCOVAS
were used to rule out MMSE scores as a result of cognitive impairments showing in the high
TSH group (Cook, et al., 2002).
The MRI and WMH results were compared to assess cardiovascular co-morbid
possibilities, 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 and
verbal recall compared to the normal TSH group. These deficits may be overcome with hormone
replacement therapy which may be a consideration for those elderly with even mild elevations of
TSH. Subjects showing signs or symptoms of dementia were ruled out, however detection is

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complex, and difficult to diagnose in the early stages (Cook, et al., 2002). The sample was
narrow due to the use of a community of highly educated elderly which may not represent the
global elderly population. The findings are significant given the wide array of testing to address
co-morbid possibilities however, and warrant further investigation into the treatment practices of
elderly patients showing even slight elevations of TSH.
Treatment may be crucial in the reversal of cognitive and mood deficits associated with
elevated THS levels. A study seeking to verify reversal of cognitive deficits in affected subjects
with increased thyroid hormone levels to the brain, found that levothyroxine (L-T4) treatment
may be effective in correcting mood and cognitive deficits in those with elevated TSH (Miller, et
al., 2006). With a control group of 14 and an untreated hypothyroid group of 10, verified by
elevated basil TSH levels, the 3 month study examined subjects of both sexes between the ages
of 18-55 pre and post treatment to verify difference. Prior to acceptance into the study, samples
were given medical, physical, neuropsychiatric, and neuropsychological screening. Independent
t test pre treatment, ANOVAS, Two-Tailed, hierarchical multiple regressions, and a HAM-D
scoring 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 reduced
HAM-D depression scores and specific memory retrieval deficits, and increased short and long
delayed recall as well as improved mood. These results showed little change in the control
group, 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 the
prevention and further deficits that may accompany thyroid dysfunction associated with
hypothyroid and dementia with severe cases (Miller, et al., 2006). Untreated hypothyroid which
with severity may cause or increase the onset and deficits found in dementia, are an important

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indication in this study that agrees with previous work by other research with the elderly and
thyroid dysfunction. Although the sample was small in this study, the testing measures may
prove to be a valuable contribution to future studies examining relationships between thyroid and
dementia for treatment outcomes. “Cognitive deficits simulating dementia can be caused by
thyroid dysfunction” (Mafrica & Fodale, 2008), and evidence found supporting thyroid
hormones relationship with the cholinergic system know to be impaired early on in those
suffering from Alzheimer’s disease (Mafrica & Fodale, 2008), suggests data from these studies
may be invaluable in determining early detection, origin, and treatment significance in long term
goals of prevention.
An interesting implication that surgery may cause or influence thyroid dysfunction also
sought to determine correlates of thyroid hormone imbalance to Alzheimer’s disease and
dementia. Euthroid sick syndrome (ESS) found in post operative patients, possibly caused by
psycho-physical stress, showed that reductions in T3 and T4 serum absent of increased TSH
occurred hours after major surgery, and in the elderly results in cognitive deficits which are
reversible (Mafrica & Fodale, 2008). Also important may be the early showing of negatively
regulated amyloid- β protein (AβPP) found in Alzheimer’s disease, which negative regulation of
the protein is also caused by imbalanced thyroid hormones; further suggesting the association of
thyroid hormones relating to the cholinergic system (Mafrica & Fodale, 2008). Thyroid
dysfunction impairs cognitive abilities including “attention, motor speed, memory, and visual-
spatial organization, even more so in the elderly with hypothyroidism, while hyperthyroid and
depression 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).

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An older study also researched the effect of hypothyroid on timing, activity, and speed
utilizing basic physical tests to track changes with hormone replacement treatment for
comparison 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 in
determining the cognitive deficits and improvements of thyroid groups compared to a control
group pre and post treatment in terms of arousal-performance (Stern, 1959). Both groups used
32 subjects of both sexes with the hypothyroid group coming from an outpatient endocrinology
clinic with diagnosed hypothyroidism with an age range of 22-67 with retest occurring after 6
months of treatment. While perhaps basic in methodology, the tests revealed that three of these
tests; tapping, audio, and visual reaction time, showed significant improvements from pre-test
measures, in the direction of the control group results. Tapping speed decreased with treatment
which was increased prior compared to the control group, and time estimation and leg lift
persists showed little change in either study between groups, even thought time estimation results
differed 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 and
hyper at the high end (Stern, 1959). Similar associations to arousal were made in studies using
rats around the same time frame using motivation to discuss results. The study using three
groups to track and determine extinction, motivation, and rates of acquisition applied a modified
Skinners box with a bar to press for food as reward incentive to create operant response. The
study used a hypothyroid group by inducing hypothyroidism using thiouracil, and a hyperthyroid
group induced with thyroxine, and a control group injected with saline (Denenberg & Meyers,

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Learning and hormone activity: I. Effects of thyroid levels upon the acquisition and extinction of
an operant response., 1958). Treatment was administered in three forms: Post weaning, upon
adulthood, or upon mastery of the operant response for each category and tested for motivation
using 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 also
found significant correlations to differences in motivation representing the findings. No
differences were observed in extinction or acquisition rate between groups with analysis of
variance, however rate of response showed lower rates for the hypothyroid group and higher for
hyperthyroid group (Denenberg & Meyers, Learning and hormone activity: I. Effects of thyroid
levels upon the acquisition and extinction of an operant response., 1958). The same authors then
performed another study to test thyroid dysfunction in rats on learned operant response retention
using starvation as motivation again with the modified Skinners box and bar press for dispensing
food (Denenberg & Meyers, Learning and hormone activity: II. Effects of thyroid levels upon
retention of an operant response and upon performance under starvation.). The hypothesis was
that the thyroid altered rat groups would experience retention impact. Utilizing the same
methods 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 operant
response and upon performance under starvation.).
The findings indicated significant lower mean responses by the thiouracel groups, with
non-starved and starved both performing similarly. This indicated these groups had similar
motivational peaks unassociated with hunger drive in comparison to the other groups. The

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authors concluded that thyroid impairment impacted motivation, however did not impact operant
recall (Denenberg & Meyers, Learning and hormone activity: II. Effects of thyroid levels upon
retention of an operant response and upon performance under starvation.). Advanced
technologies developed since these studies such as neuroimaging may prove useful in adaptation
models using similar techniques to induce hypo and hyper thyroid states for study in animals. To
determine brain reactions and changes with thyroid dysfunction over ages and in conjunction
with dementia and Alzheimer’s findings for comparison, may prove valuable for research
regarding the elderly response to thyroid dysfunction and the cognitive deficits associated.
Updated techniques and technology may help to validate or determine the findings in outdated
research, which applied to diseases in the elderly such as dementia and Alzheimer’s may allow
for renewed understanding and new or improved results lending to cognitive ability impacts and
origins 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, but
caused by specific retrieval deficits (Bauer, Goetz, Glenn, & Whybrow, 2008), which
specificities have also been indicated and highlighted in studies throughout this paper. Thyroid
metabolism in the adult brain being disrupted can also lead to two common causes of thyroid
dysfunction: Autoimmune disorders such as Graves disease result in hyperthyroidism and
Hashimototo’s thyroiditis result in hypothyroidism. In addition to impairing mood and
intellectual performance, severe forms of hypothyroidism can result in severe depression and
even “mimic dementia” which may result in irreversible dementia when left untreated (Bauer,
Goetz, Glenn, & Whybrow, 2008). Less severe forms affecting patients with treatment will

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likely 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 the
medical database. Given the important and relevant data provided in the medical research on this
topic, 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 with
possible symptoms of thyroid dysfunction may miss-diagnose or delay vital treatment id thyroid
dysfunction remains undetected, particularly in the elderly population exhibiting early signs of
dementia. Many of the studies utilized extensive testing to determine findings, which may be
helpful if data is cross referenced to determine best testing outcomes and measures specifically
for thyroid hormone related studies. Further research should extend the studies in length to
accommodate proper treatment satisfaction to euthyroid levels before or in addition to post
testing 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 on
patients having complete thyroidectomies, or removal of the thyroid gland. Studies may benefit
from researching this category of patients with the ability to track average time for full return to
euthyroid status and deficits encountered pre and post surgery.
Conclusion
The studies performed allow for considerable opportunities to further past research using
improved technology and updated knowledge of thyroid dysfunction, and may give insight into

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complex and irreversible diseases consuming so many resources for answers. Ultimately the
fields of neuroscience and psychology may provide much needed insight into thyroid metabolism
and cognitive deficits resulting from dysfunction by combining recourses and research focused
on 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 a
cognitive, physical, and emotional impact in the negative direction when imbalanced, and further
investment in research among age groups and severity is warranted and perhaps even holds the
key too many solutions affecting our elderly population.

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