Hypothyroidism does not worsen rate of cognitive decline for perimenopausal women
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Key takeaways:
- Hypothyroidism did not have a significant effect on a decline in processing speed over time in SWAN.
- Working memory and episodic memory did not significantly change during follow-up.
Women with hypothyroidism receiving levothyroxine treatment experienced similar cognitive decline during menopause as those without thyroid disease, according to data published in Thyroid.
In the Study of Women’s Health Across the Nation (SWAN), women aged 42 to 52 years at baseline completed cognitive function tests assessing processing speed, working memory and episodic memory during a mean follow-up of 13 years. During follow-up, researchers found declines in processing speed were not significantly greater for women with hypothyroidism, and no decreases in working memory or episodic memory were observed for the full study group.
“Some cognitive decline during menopause and in the years after is expected, and hypothyroidism, if properly treated, would not be expected to make this worse,” Matthew Ettleson, MD, clinical fellow at the University of Chicago, told Healio. “Therefore, if there is a decline in cognitive function beyond what is expected, a thorough investigation is warranted, including thyroid function testing. However, for most women, if thyroid function testing is normal (whether they have hypothyroidism or not), I would consider alternative explanations for the decline in cognitive function.”
Researchers obtained cognitive function data from 2,033 SWAN participants, of whom 227 had levothyroxine-treated hypothyroidism (mean age, 49.8 years; 59.9% white) and 1,806 had no thyroid disease (mean age, 50 years; 45.1% white). Cognitive function testing was conducted between 2000 and 2017. Processing speed was measured through the Symbol Digit Modalities Test. Working memory was evaluated using a digit span backward evaluation. The East Boston Memory Test was used to assess episodic memory.
In the initial cognitive function test, women with hypothyroidism had a higher processing speed score (mean score, 56.5 vs. 54.4; P = .006) and working memory score (mean score, 6.8 vs. 6.4; P = .018) than women without thyroid disease. No difference in episodic memory score was observed between the two groups at baseline.
During follow-up, participants had a significant annual decline in processing speed (beta = –0.013; P < .001). Hypothyroidism did not have a significant effect on cognitive function decline. There was no significant decline in working memory or episodic memory decline during the study, and hypothyroidism did not have a significant effect on the change in either assessment score.
“In designing this study, my concern was that we would find a difference [between groups], and it is reassuring that we did not,” Ettleson said. “However, the literature remains very mixed on this topic, so we shouldn’t be surprised by the findings. We only had data available on a select number of cognitive tests. Therefore, it’s possible that other domains of cognitive function that were not tested were indeed worse in those with hypothyroidism.”
Ettleson also noted there was a limited amount of thyroid function data available in SWAN, making it difficult for researchers to control for thyroid hormone levels in the study.
“We still need to learn more about those patients that have persistent symptoms on levothyroxine,” Ettleson said. “Are there some unique characteristics that could help clinicians better identify and treat these individuals?”
For more information:
Matthew Ettleson, MD, can be reached at matthew.ettleson@uchospitals.edu.
Perspective
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Hypothyroidism affects 3% to 7% of the U.S. population, making it a common endocrine disorder primarily treated with levothyroxine. Despite biochemical control, 5% to 10% of patients report persistent symptoms such as mood disturbances, fatigue and "brain fog." The etiology of this is poorly understood and is believed to be multifactorial. Factors like menopause, coexisting autoimmune disorders, sleep apnea and inadequate conversion of thyroxine to triiodothyronine are among the cited reasons. Additionally, there are concerns that levothyroxine-treated patients may experience cognitive decline with age compared to euthyroid individuals.
This study by Ettleson and colleagues aimed to explore the relationship between hypothyroidism and cognitive function changes in women across the menopause transition. The Study of Women’s Health Across the Nation (SWAN) is a longitudinal, multidisciplinary investigation examining health changes in women from midlife to early old age. In this prospective cohort study, cognitive function trajectories were analyzed in women with and without hypothyroidism across three domains: processing speed, working memory and episodic memory.
The study included 2,033 women, with 227 meeting the criteria for levothyroxine-treated hypothyroidism and 1,806 forming the control group. The mean duration of follow-up was 13 years. At baseline, women with levothyroxine-treated hypothyroidism exhibited higher scores in processing speed and working memory. However, cognitive function declined at a similar rate in both groups over time and results remained consistent after adjusting for clinical and sociodemographic factors. There was also no significant difference in self-reported cognitive decline between the hypothyroid and control groups.
This study concludes that cognitive function decline during midlife is not worse in women treated for hypothyroidism compared to those without thyroid disease. The data on residual cognitive deficits in patients with levothyroxine-treated hypothyroidism is conflicting, with some studies suggesting that levothyroxine treatment is not sufficient in a small group of patients. This has led to a call for more studies of various outcomes in patients treated with levothyroxine compared to combination therapies.
This study highlights the need to explore other factors that may contribute to patient dissatisfaction with treatment and reassures clinicians and patients that hypothyroidism does not adversely affect cognition over time.
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