Abstract
Subclinical hypothyroidism (SCH), defined as elevated thyroid stimulating hormone (TSH) and normal thyroid hormone levels, and cognitive impairment are both common in older people. While the relation between overt hypothyroidism and cognitive impairment is well established, data on the association between SCH and cognitive impairment are conflicting. This systematic review and meta-analysis was performed to assess available evidence on the association of SCH with cognition in community dwelling, relatively healthy older adults. PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, PsycINFO, and Academic Search Premier (January 1966 to April 1, 2015) were searched without language restrictions, as were references of key articles, for studies on the association between SCH and cognition in older adults (>60 years). These studies were reviewed by two independent reviewers according to predefined criteria for eligibility and methodological quality, and data were extracted using standardized forms. Of the 844 reports initially identified, 270 remained after exclusion of duplicates. Of the 270, 15 studies comprising 19,944 subjects, of whom 1,199 had subclinical hypothyroidism were included. Data from the 15 studies was pooled, and meta-analyzed cross-sectionally for global cognition [assessed by Mini-Mental State Examination (MMSE)], executive function, and memory, using random effects models. Pooled effect size (ES) for MMSE was −0.01 (95% CI −0.09, 0.08), with heterogeneity (I2) of 55.1%. Pooled ES was < 0.001 (95% CI −0.10, 0.09) for executive function (I2 = 13.5%), and 0.01 (95% CI −0.12, 0.14) for memory (I2 = 46.9%). In addition, prospective analysis including four studies showed pooled ES of 0.033 (95% CI −0.001 − 0.067) for MMSE (I2 < 0.001%), indicating that subclinical hypothyroidism was not significantly associated with accelerated cognitive decline. This systematic review and meta-analysis provides no evidence that supports an association between SCH and cognitive impairment in relatively healthy older adults.
Highlights
Overt adult onset hypothyroidism, which is marked by elevated thyroid stimulating hormone (TSH) levels and reduced levels of circulating thyroid hormones, has been associated with increased risk of deficits in specific cognitive domains including attention, concentration, memory, perceptual function, language, executive function, and psychomotor speed (Constant et al, 2005; Davis and Tremont, 2007; Samuels, 2008; Correia et al, 2009)
Controversies persist as to whether subclinical hypothyroidism (SCH), defined as mild elevation of TSH in the presence of normal free thyroxine, is associated with declines in these specific cognitive domains. This is especially relevant in the older adults, as the prevalence of subclinical hypothyroidism increases with age and is estimated to be up to 22% in women aged more than 60 years and somewhat lower in men (Sawin et al, 1985; Canaris et al, 2000)
Of the 270 reports, 210 were excluded that were unrelated to the association between subclinical hypothyroidism and cognition in the elderly (Figure 1), leaving 60 articles for full text analysis
Summary
Overt adult onset hypothyroidism, which is marked by elevated thyroid stimulating hormone (TSH) levels and reduced levels of circulating thyroid hormones, has been associated with increased risk of deficits in specific cognitive domains including attention, concentration, memory, perceptual function, language, executive function, and psychomotor speed (Constant et al, 2005; Davis and Tremont, 2007; Samuels, 2008; Correia et al, 2009).
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