Changes in Serum Thyroid Function Predict Cognitive Decline in the Very Old: Longitudinal Findings from the Newcastle 85+ Study

Abstract

Background: Low serum thyrotropin (TSH) has been associated with an increased risk of cognitive impairment in observational studies of older individuals, but the mechanism underlying this is unclear. We investigated the association between changes in thyroid status and cognitive impairment in very old adults, using prospective data from the Newcastle 85+ study. Method: A cohort of 85-year-old individuals was assessed for health status and thyroid function. Complete data from a comprehensive multidimensional measure of health and repeat thyroid function were available for 642 participants with normal free thyroid hormones and TSH levels ranging between 0.1 and 10 mU/L. Cognitive performance, assessed using Mini-Mental State Examination (MMSE) and Cognitive Drug Research battery was examined by using linear mixed, logistic regression, and Cox proportional hazard models in relation to baseline and 3-year changes in serum TSH, free thyroxine (fT4), and free triiodothyronine (fT3). Results: Over 3 years, declining serum TSH was associated with reductions in fT4 and fT3, and an increased risk of incident cognitive impairment by 5 years (odds ratio1.77 [95% confidence interval: 1.19-2.61]; p = 0.004). A greater reduction in MMSE score was associated with larger TSH decline, at 3 ( p = 0.001) and 5 years ( p < 0.001), respectively. Steady fT4 concentrations were found in participants with rising TSH. Conclusions: In contrast to physiological expectation, in this group of 85-year-olds, a declining serum TSH was associated with reductions in free thyroid hormones over time. A decreasing serum TSH trajectory over time anticipated cognitive decline in later life. Declining TSH concentrations are a biomarker for cognitive impairment in later life.

Thyroid Function and the Risk of Alzheimer's Disease: A Mendelian Randomization Study

“…This study's main aim was to explore the causal relationships between thyroid function and AD with the use of bidirectional MR techniques. We showed that increased levels of genetically predicted TSH within the normal range were significantly associated with a decreased risk of AD, in agreement with previous evidence (5,7,8). We further explore the effect of full range TSH levels on AD risk by using summary statistics from different data sets, including data from the largest meta-analysis from HUNT+MGI+ThyroidOmics along with analyses only using data from the HUNT study, as a more homogeneous set.…”

“…Another study by van Osch et al (4) also found that lower TSH levels within the reference range were associated with an increased AD risk; however, in contrast to the Framingham study, these results were independent of sex. Gan et al report that with older age, the feedback between TSH and fT4 attenuates (7). Thus, decreased TSH is associated with decreased fT4, which is associated with cognitive decline.…”

Sex-, and neurodegeneration-dependent effect modification in the association between thyroid function and cognitive impairment in non-depressed, non-demented elderly

“…(31) In older populations (85 years), a longitudinal decrease in TSH levels was associated with a concomitant reduction in MMSE scores over a three-and five-year follow-up period. (32) Thyrotoxicosis is a rarer condition in which patients present very high thyroid hormones either of endogenous or exogenous etiology (corresponding to very low TSH). In a study including 65931 elderly patients aged 65 years and older, thyrotoxicosis was associated with a significantly higher risk of cognitive decline.…”