Older adults with hypothyroidism may be at higher risk of developing dementia, especially if they take thyroid hormone replacement therapy, new research suggests.
Investigators analyzed medical records of almost 8000 adults (mean age, 75 years) who were newly diagnosed with dementia.
After adjusting for other health and demographic factors that could affect dementia risk, results showed a history of hypothyroidism was associated with an 81% increased risk of developing dementia.
Moreover, individuals with hypothyroidism who took medication for their condition were more than three times as likely to develop dementia compared with those who did not take medication.
“Thyroid function tests should be considered for patients with memory decline or dementia concerns,” lead author Chien-Hsiang Weng, MD, MPH, clinical assistant professor, Warren Alpert Medical School of Brown University, Providence, Rhode Island, told Medscape Medical News.
“It is important to identify patients with thyroid disorders and correct their thyroid function as early as possible to help reduce the risk of several medical conditions, including dementia,” Weng said.
The findings were published online today in the journal Neurology.
Rapidly Aging Population
In recent decades, studies have focused on the effect of thyroid hormones T3 and T4 and trophic thyroid-stimulating hormone (TSH), especially as manifested in the form of subclinical hypothyroidism, on dementia risk. However, results have been “conflicting,” the investigators write.
In countries with an iodine-rich diet, the prevalence of hyperthyroidism and hypothyroidism is an estimated 0.2%–1.3% and 1%–2%, respectively, with women disproportionately affected. Incidence rises as individuals get older, reaching as much as 7% in those aged 85-89 years old.
In Taiwan, the prevalence of dementia rose from 6.8% in 1992 to 11.1% in 2012, in a “rapidly aging population.” Thus, there is a “greater need to expand upon and scrutinize these understudied correlative findings with thyroid disorders,” especially because most previous research was conducted in non-Asian populations, the researchers write.
Weng said he has been investigating the association between thyroid disorder and several other diseases, such as cancers or chronic medical conditions, in the past several years.
“As a primary care physician, I’ve been seeing patients with memory decline quite often in my daily practice and observed that many of them had thyroid disease,” he said.
“With the lack of strong clinical evidence, I decided to design and conduct a large-scale study to investigate this association,” Weng added.
The investigators conducted a nationwide, population-based, case-control study using the Taiwanese National Health Insurance Research database. Among the adult participants (n = 15,686) half were diagnosed with dementia between 2006 and 2013 (mean age, 74.9 years) while the other half did not have dementia (mean age, 74.5 years). Both groups were slightly predominantly female (51.8%).
Participants were matched 1:1 by age, sex, and index date, after which the researchers ascertained whether the patients had a history of thyroid disorders.
To be included in the study, the patient must have received the diagnosis of thyroid disorder in three or more clinical visits. In addition, the initial diagnosis of thyroid disorder had to have occurred 1 year before the first dementia diagnosis and 1 year before the index date in the control group.
Investigators adjusted their findings for an array of potential confounders, including age, sex, and history of several illnesses including hypertension, diabetes, coronary artery disease, depression, hyperlipidemia, alcohol dependence, tinnitus, hearing loss, and radioactive iodine treatment.
“Robust” Evidence
Among the participants, 235 had thyroid disease. Of these, 102 had hypothyroidism and 133 had hyperthyroidism.
Having a history of several medical conditions was associated with an increased risk of developing dementia in the overall study population.
Table. Risk of developing dementia by history of medical condition
| Medical condition | % with vs without who developed dementia | P value |
|---|---|---|
| Hypertension | 47.3% vs 40.9% | < .001 |
| Diabetes | 27.3% vs 17.8% | < .001 |
| Coronary artery disease | 15.0% vs 12.8% | < .001 |
| Depression | 2.0% vs 0.3% | < .001 |
| Tinnitus | 2.1% vs 1.6% | .013 |
| Alcohol dependence | 0.5% vs 0% | < .001 |
In addition, 0.9% of those with dementia were identified with hypothyroidism and 1% were identified with hyperthyroidism vs 0.4% and 0.7%, respectively, in the nondementia group (P = .001).
After adjusting for covariates, among participants 65 years and older, a history of hypothyroidism was associated with an 81% increased risk of being diagnosed with dementia (adjusted odds ratio [aOR], 1.81; 95% CI, 1.14 – 2.87; P = .01). This association was not found in patients between the ages of 50 and 65 years.
There was also no significant link between hyperthyroidism and dementia; and, in patients older than age 65 who acquired hypothyroidism after hyperthyroidism treatment, there was no statistically significant increased risk of developing dementia.
When the investigators conducted a subgroup analysis of patients 65 years and older, they found the association between dementia and thyroid disorders was the most significant among those with hypothyroidism who were taking hypothyroidism medication (aOR, 3.17; 95% CI, 1.04 – 9.69; P = .043) vs those with hypothyroidism not taking medication for their condition.
Weng suggested this finding “might be due to the fact that these patients had more severe thyroid disorder and is unlikely to be related [side effects of] the medication itself.”
A limitation of the study was that the investigators “were not able to obtain the laboratory data for each patient and the severity of the thyroid disease,” Weng noted. However, participants who took thyroid medication such as levothyroxine “were more likely to have more severe hypothyroidism or be symptomatic,” he said.
Because the “biological and molecular pathways behind this association are similar across ethnicities/races, the findings from our large-scale study offer robust evidence to the literature and are possibly generalizable to non-Asian people,” said Weng.
However, he noted that the study was observational, “and therefore doesn’t prove that hypothyroidism ’causes’ dementia, only that there is an association.”
Timely Referral Needed
Commenting for Medscape Medical News, Chi-Ying (Roy) Lin, MD, MPH, assistant professor of neurology, Alzheimer’s Disease and Parkinson’s Disease Centers, Baylor College of Medicine, Houston, Texas, said this was an “excellent study” that provides additional evidence for a relationship between hypothyroid disorder and dementia, “especially from the generalizability point of view.”
Lin, who was not involved with the research, noted that the study population was comprised of individuals from Taiwan, “mitigating the gap that the majority of current studies were conducted in non-East Asian populations.”
Moving forward, “practicing clinicians should proactively test thyroid function when assessing people with cognitive symptoms,” he said.
Lin also recommended timely referral to an endocrinologist in the event of “equivocal results, so as not to miss the treatment opportunity.”
The study received no targeted funding. Weng, the other investigators, and Lin report no relevant financial relationships.
Neurology. Published online July 6, 2022. Abstract
Batya Swift Yasgur, MA, LSW is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).
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