Reduced cerebrospinal fluid level of thyroxine in patients with Alzheimer's disease

Abstract

Little is known of the association between thyroid hormones in the central nervous system and Alzheimer's disease (AD). We determined thyroid hormone levels in serum and cerebrospinal fluid (CSF) in a well-defined homogeneous mono-center population. Fifty-nine consecutive patients under primary evaluation for cognitive impairment were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n=31), patients with stable MCI (SMCI, n=13), patients with other dementias (n=15), and healthy controls (n=19). Thyroid hormones in serum and CSF and AD biomarkers in CSF were analyzed using established immunochemical assays. Cognitive impairment was estimated using mini-mental state examination (MMSE). Serum levels of free and total thyroxine (T4) and triiodothyronine (T3) were similar in all groups whereas a marginal increase in serum thyroid-stimulating hormone (TSH) level was observed in the AD patients. The CSF level of total T4 was decreased in patients with AD and other dementias compared to SMCI (both P=0.01) and healthy controls (both P=0.001), whereas CSF levels of TSH and total T3 were unchanged. In the total study population, CSF total T4 level correlated positively with MMSE score (r=0.26, P<0.05) and negatively with CSF total-tau (T-Tau) level (r=-0.23, P<0.05). Patients with AD as well as other dementias had signs of mild brain hypothyroidism, which could only to a small extent be detected in serum values.