Decreasing TSH linked to decline in cognitive functioning for older adults
Older adults with decreasing serum thyroid-stimulating hormone levels were more likely than those with a steady level to experience cognitive decline, according to findings published in Thyroid.
Additionally, Earn H. Gan, PhD, an academic clinical lecturer at the Translational and Clinical Research Institute, International Centre for Life at Newcastle University in the United Kingdom, and colleagues observed that older adults with declining serum TSH also had reductions in free thyroxine and free triiodothyronine, contradicting physiological expectations.
“This suggests for the first time that falling serum TSH in advanced old age may reflect a pattern of central hypothyroidism, possible owing to changes in hypothalamo-pituitary state or an increasing burden of nonthyroidal illness with age, rather than mild thyroid hormone excess,” the researchers wrote.
Researchers analyzed data from participants in Newcastle 85+, a population-based study of adults aged 85 years visiting general practices in Newcastle and North Tyneside in the United Kingdom. Participants completed health questionnaires and underwent anthropometric measurements, physical tests and cognitive assessments at baseline. Fasting blood samples were collected at the participant’s residence by a research nurse. Venipuncture was performed to measure thyroid function. The Mini-Mental State Examination was used to measure cognitive function. Participants scoring 25 of 30 points or worse were defined as having incident cognitive impairment. Follow-up exams took place 3 and 5 years after baseline.
Researchers included 642 participants with normal thyroid hormone and TSH levels at baseline in the analysis (58.1% women); 348 had thyroid function tests performed at the 3-year follow-up, and 63.5% of these had decreasing TSH. Adults with decreasing TSH had a mean decline from 2.67 mU/L to 1.8 mU/L. For those with increasing TSH, levels went from 1.85 mU/L to 2.82 mU/L. Adults with declining TSH also had a decline in free T4, whereas free T4 remained steady in participants with increasing TSH. All participants had declines in free T3 over time.
Of those with thyroid function measured at 3 years, 346 had cognitive function reassessed at 3 years and 276 were reassessed at 5 years. Changes in serum TSH at 3 years were associated with a change in cognitive function at 3 years (beta = 0.31; 95% CI, 0.01-0.611; P = .045) and at 5 years (beta = 0.52; 95% CI, 0.08-0.95; P = .02).
Adults with a reduction in TSH from baseline to 3 years were more likely to have incident cognitive impairment at 5 years (OR = 1.77; 95% CI, 1.19-2.61; P = .004), but not at 3 years. A decrease in TSH was associated with a 3-point or more decrease in the Mini-Mental State Examination score over 5 years (OR = 1.45; 95% CI, 1.01-2.09; P = .049). The association was stronger for adults with normal cognitive function at baseline (OR = 1.73; 95% CI, 1.06-2.8; P = .027).
In the full study cohort, lower free T3 at baseline was associated with worse initial cognitive functioning (P = .002). For those with good cognitive function at baseline, lower baseline free T3 was associated with worse cognition over time (P = .031), whereas lower baseline free T4 was associated with better cognitive function over time (P = .005). After adjusting for all covariates, having a higher free T3 level was protective against cognitive impairment (HR = 0.77; 95% CI, 0.6-0.99; P = .04).
“We show, for the first time, that a decreasing TSH trajectory anticipates cognitive decline in later life,” the researchers wrote. “Further studies are now required to better understand the significance of changes in thyroid function in this age group and their relationship to cognitive outcome.”