Abstract

BackgroundSubclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).MethodsProspective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.ResultsSubclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.ConclusionWe found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.

Highlights

  • Subclinical thyroid dysfunction, defined biochemically as a normal serum level of free thyroxine (FT4) in the presence of a high or low level of thyroid stimulating hormone (TSH), are a common finding among the elderly population with a prevalence of up to 20% [1]. Both subclinical hyper- and hypothyroidism have been implicated as risk factors for cognitive decline, the literature regarding these associations shows inconsistent results [2,3,4,5,6,7,8]

  • Hypothyroidism is associated with hypertension [10,11], and higher levels of total cholesterol and low-density lipoprotein (LDL) cholesterol [12,13,14], both of which increase the risk of atherosclerosis [15,16]

  • Both subclinical hyperthyroidism and hypothyroidism are associated with cardiovascular disease and could be important contributors to cognitive decline

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Summary

Introduction

Subclinical thyroid dysfunction, defined biochemically as a normal serum level of free thyroxine (FT4) in the presence of a high or low level of thyroid stimulating hormone (TSH), are a common finding among the elderly population with a prevalence of up to 20% [1] Both subclinical hyper- and hypothyroidism have been implicated as risk factors for cognitive decline, the literature regarding these associations shows inconsistent results [2,3,4,5,6,7,8]. It is well established that subclinical hyperthyroidism is related to an increased risk of atrial fibrillation [15,18,19], which is an important risk factor for stroke Both subclinical hyperthyroidism and hypothyroidism are associated with cardiovascular disease and could be important contributors to cognitive decline. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)

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