: The role of thyroid function in Alzheimer's disease (AD) has been subject to a number of studies during the last years. We investigated the possible relationship between plasma levels of the biologically active free form of thyroxin (fT4) and cognitive function in 227 outpatients with mild to moderate Alzheimer s disease (AD) in a cross-sectional study design. A significant negative correlation was found between plasma fT4-levels and Mini-Mental state examination (MMSE) score (Spearman Rho = -0.14, p=0.04). When the lowest quartile of fT4-levels (<15.1 pmol/l) was compared to the highest quartile (>19.0 pmol/l), statistically significant lower mean MMSE-scores were seen in the group with the highest fT4-levels (p<0.05, ANOVA). The mean difference between the 1st and the 4th quartile of fT4 was 2.6 MMSE-score points. No correlations were found between plasma total T4-levels, plasma total T3-levels, plasma TSH-levels and the MMSE score (p>0.05). When fT4 quartile groups were compared for depression measured in the Geriatric Depression Score (GDS 15), a slightly higher score was seen in the 1s and 2nd compared to the 3rd and 4th quartile groups without reaching statistical significance (1st quartile of fT4: GDS 5.2 +/- 3.8; 2nd: 5.3 +/- 4.0; 3rd: 4.4 +/- 3.4; 4th: 4.5 +/- 3.8) pointing to a reverse correlation of fT4 levels and depressive mood. This study leads to the conclusion that high levels of plasma fT4 might result in a worsening of cognitive impairment and a positive effect on depressive mood in AD.