Thyroid function and cognitive decline in the MRC Cognitive Function and Ageing Study

Hypothyroidism and subclinical hyperthyroidism have both been associated with cognitive impairment and dementia. The association between thyroid stimulating hormone (TSH), free thyroid hormone or thyroxine (FT4) levels and cognition was investigated at baseline and after a 2 year follow-up in 1047 participants over 64 years of age, without physical frailty or severe cognitive impairment at baseline. Results indicated that high log transformed TSH levels were associated with lower MMSE performance (B=-0.24 (S.E.=0.09), 95% CI=-0.41 to -0.07) at baseline, independent of FT4, age, sex, education and mood, and, in separate analyses, cardiovascular (risk) factors. Importantly, half of all hypothyroid cases were untreated and unaware of having this disorder. In analyses which excluded cases with thyroid disorders, stroke and those suspected of possible dementia/cognitive impairment (MMSE less than 25) or psychiatric mood disorders at baseline, high-normal FT4 levels were associated with worse MMSE performance and a greater risk for a drop of at least 4 points on the MMSE after 2 years (per pmol/l O.R.=1.13, 95% C.I.=1.03-1.22). In conclusion, elderly patients with cognitive impairment should always be assessed for hypothyroidism. It is unclear why high normal FT4 levels were independently associated with accelerated cognitive decline in those without overt thyroid disease. Other studies found that thyroxine can generate oxidative stress and damage neurons. Treatment with thyroxine in those without thyroid disease (as is sometimes done in anti-ageing clinics) is thus not recommended on the basis of these data and the optimal therapeutic level in the elderly may be lower than is assumed.