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Dementia risk increases in adults with subclinical hyperthyroidism
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Adults with subclinical hyperthyroidism may have an increased risk for dementia and a fast decline in their mini-mental state examination score over time, according to recently published findings.
Nicolas Rodondi, MD, MAS, of the department of general internal medicine at Bern University Hospital in Switzerland, and colleagues evaluated data from 11 prospective cohort studies that followed 16,805 participants for a median of 44.4 months to determine the risk for dementia and cognitive decline related to subclinical thyroid dysfunction.
The risk for dementia was examined by five studies for subclinical hyperthyroidism and six for subclinical hypothyroidism. Mini-mental state examination (MMSE) score decline was examined by five studies for subclinical hyperthyroidism and seven for subclinical hypothyroidism.
Compared with euthyroid participants, those with subclinical hyperthyroidism had a pooled RR of 1.67 (95% CI, 1.04-2.69) for dementia and a pooled RR of 1.67 (95% CI, 0.79-3.51) for Alzheimer’s disease. Participants with subclinical hypothyroidism had a pooled RR of 1.14 (95% CI, 0.84-1.55) for dementia and a pooled RR of 0.95 (95% CI, 0.52-1.71) for Alzheimer’s disease compared with euthyroid participants.
From baseline, the pooled mean difference in MMSE decline for cognitive function per year was 0.01 among participants with subclinical hyperthyroidism; changes were similar in participants with subclinical hypothyroidism and those with euthyroidism.
“Our systematic review and meta-analysis indicates that [subclinical hyperthyroidism], but not [subclinical hypothyroidism], might be associated with a modestly elevated risk of dementia,” the researchers wrote. “Neither [subclinical hyperthyroidism] nor [subclinical hypothyroidism] were significantly associated with a faster decline in MMSE over time, as compared to euthyroidism. Available data were limited, and additional larger, high-quality prospective cohort studies are needed.” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Fabio Monzani
This meta-analysis of eleven prospective cohort studies shows that subclinical hyperthyroidism might be associated with an elevated risk for dementia, while subclinical hypothyroidism is not, and neither condition is associated with faster decline in MMSE over time. The main implication of this finding is that subclinical hyperthyroidism might represent a potentially treatable risk factor for dementia, while subclinical hypothyroidism should be not considered potentially detrimental in the aging population. Thus, physicians might be encouraged to undertreat mild thyroid failure in patients with or without cognitive impairment.
As correctly stated by the authors, all the studies were performed in participants with mean age older than 65 years, and all but two studies assessed thyroid function tests only at baseline. It should be underlined that thyroid hormone levels are regulated by the hypothalamic-pituitary-thyroid axis, which has a unique set-point for each individual, and a wide variety of factors can modulate the set-point, including illness and aging. Moreover, Andersen and colleagues (J Clin Endocrinol Metab. 2002;doi:10.1210/jcem.87.3.8165) clearly showed that each individual had a unique thyroid function, and the individual reference ranges for test results are narrow compared with laboratory reference ranges. Thus, the actual assessment of thyroid status is still a challenge not completely addressed by the determination of circulating thyroid hormone levels, especially in the elderly. Indeed, the possibility of a certain degree of over diagnosis of subclinical hypothyroidism should not be excluded at least in older people (aged > 75-80 years), and some participants with subclinical hypothyroidism at baseline may have normalized to euthyroidism over time.
Keeping in mind these considerations, the results of the current meta-analysis appear not completely at odds with our previous meta-analysis that found a significant risk for the primary composite endpoint (reduced MMSE, Wechsler Memory Scale-Revised, total memory quotient and Wechsler Adult Intelligence Scale scores) only in subclinical hypothyroid individuals younger than 75 years (Pasqualetti G, et al. J Clin Endocrinol Metab. 2015;doi: 10.1210/jc.2015-2046). Overall, these considerations do not allow us to generalize the results of the current study, and no conclusions on the benefits or risks of thyroid medication on cognitive function and behavior of subclinical hypothyroidism patients can be drawn, especially in young adults. Thus, the final statement by Carole Rieben and colleagues on the limitation of currently available data and the need of additional large, high-quality prospective cohort studies is absolutely appropriate.
Disclosure:Monzani reports no relevant financial disclosures.
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