Thyroid hormones, dementia, and atrophy of the medial temporal lobe

Context: Thyroid function has been related to Alzheimer disease (AD), but it remains unclear whether thyroid dysfunction results from or contributes to developing AD. Objective: The objective of the study was to determine the association between thyroid function and both medial temporal lobe atrophy on brain magnetic resonance imaging (MRI) as putative early sign of AD and risk of dementia. Design and Participants: This was a population-based cohort study among 1077 elderly subjects aged 60-90 yr and dementia free at baseline (1995-1996). Main Outcome Measures: Nonfasting serum levels of TSH, free T-4 (fT(4)), T-3, and rT(3) were available in 1025 subjects followed up for incident dementia until 2005. In a subset of 489 nondemented elderly, we assessed volumes of the hippocampus and amygdala on brain MRI. Subjects using thyroid medication were excluded. Results: During 5657 person-years of follow-up (mean 5.5 yr), 63 subjects were diagnosed with dementia (46 with AD). TSH and thyroid hormones were not associated with risk of dementia or AD. TSH and T3 were also not related to brain atrophy, whereas nondemented subjects with higher fT(4) levels had more hippocampal and amygdalar atrophy on MRI. Similar associations were found for rT3. Excluding subjects with thyroid disorders or incipient AD did not change the results. Conclusion: In our study, TSH was related neither to risk of AD nor with early MRI markers thereof, arguing against an important role of thyroid function in the development of AD. Whether the association of higher fT4 and rT3 levels with brain atrophy on MRI has functional significance remains to be elucidated.