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Hot Topics in Translational Endocrinology - Endocrine Research:
- Bu B. Yeap,
- Helman Alfonso,
- S. A. Paul Chubb,
- Gaurav Puri,
- Graeme J. Hankey,
- Leon Flicker,
- and Osvaldo P. Almeida
Higher Free Thyroxine Levels Predict Increased Incidence of Dementia in Older Men: The Health In Men Study <cite><abbr title="Journal of Clinical Endocrinology & Metabolism" class="site-title">JCEM</abbr> 2012 97: E2230-E2237; doi:10.1210/jc.2012-2108 </cite>
Abstract
Context: Both hypothyroidism and subclinical hyperthyroidism hinder cognitive function.
Objective: We aimed to determine whether more subtle alterations of thyroid hormone levels predict increased incidence of dementia in aging men.
Participants and Design: Community-dwelling men aged 70?89 yr participated in this prospective longitudinal study.
Main Outcome Measures: The Standardized Mini-Mental State Examination was performed at baseline (2001?2004), and circulating TSH and free T4 (FT4) were assayed. Men with known thyroid disease or dementia, or Standardized Mini-Mental State Examination scores below 24 were excluded from follow-up. New-onset dementia, defined by International Classification of Disease (ICD) codes, was ascertained using data linkage (2001?2009).
Results: During follow-up, 145 of 3401 men (4.3%) were diagnosed for the first time with dementia. Men who developed dementia had higher baseline FT4 (16.5 ? 2.2 vs. 15.9 ? 2.2 pmol/liter, P = 0.004) but similar TSH (2.2 ? 1.4 vs. 2.3 ? 1.6 mU/liter, P = 0.23) compared with men who did not receive this diagnosis. After adjusting for covariates, higher FT4 predicted new-onset dementia (11% increased risk per 1 pmol/liter increase in FT4, P = 0.005; quartiles Q2?4 vs. Q1: adjusted hazard ratio = 1.76, 95% confidence interval = 1.03?3.00, P = 0.04). There was no association between TSH quartiles and incident dementia. When the analysis was restricted to euthyroid men (excluding those with subclinical hyper- or hypothyroidism), higher FT4 remained associated with incident dementia (11% increase per unit increment, P = 0.03; Q2?4 vs. Q1: adjusted hazard ratio = 2.02, 95% confidence interval = 1.10?3.71, P = 0.024).
Conclusions: Higher FT4 levels predict new-onset dementia in older men, independently of conventional risk factors for cognitive decline. Additional studies are needed to explore potential underlying mechanisms and to clarify the utility of thyroid function testing in older men at risk of dementia.
Footnotes
Abbreviations:
FT4
Free T4
HR
hazard ratio
Q2
quartile 2
SMMSE
Standardized Mini-Mental State Examination
WADLS
Western Australian Data Linkage System.
Received May 1, 2012.
Accepted August 23, 2012.
Copyright ? 2012 by The Endocrine Society