Is Subclinical Thyroid Dysfunction in the Elderly Associated with Depression or Cognitive Dysfunction?

17 October 2006 | Volume 145 Issue 8 | Pages 573-581

Background: Widespread use of automated sensitive assays for thyroid hormones and thyroid-stimulating hormone (TSH) has increased identification of mild thyroid dysfunction, especially in elderly patients. The clinical significance of this dysfunction, however, remains uncertain, and associations with cognitive impairment, depression, and anxiety are unconfirmed.

Objective: To determine the association between mild thyroid dysfunction and cognition, depression, and anxiety in elderly persons.

Design: Cross-sectional study. Associations were explored through mixed-model analyses.

Setting: Primary care practices in central England.

Patients: 5865 patients 65 years of age or older with no known thyroid disease who were recruited from primary care registers.

Measurements: Serum TSH and free thyroxine (T₄) were measured. Depression and anxiety were assessed by using the Hospital Anxiety and Depression Scale (HADS), and cognitive functioning was established by using the Middlesex Elderly Assessment of Mental State and the Folstein Mini-Mental State Examination. Comorbid conditions, medication use, and sociodemographic profiles were recorded.

Results: 295 patients met the criteria for subclinical thyroid dysfunction (127 were hyperthyroid, and 168 were hypothyroid). After confounding variables were controlled for, statistically significant associations were seen between anxiety (HADS score) and TSH level (P = 0.013) and between cognition and both TSH and free T₄ levels. The magnitude of these associations lacked clinical relevance: A 50-mIU/L increase in the TSH level was associated with a 1-point reduction in the HADS anxiety score, and a 1-point increase in the Mini-Mental State Examination score was associated with an increase of 50 mIU/L in the TSH level or 25 pmol/L in the free T₄ level.

Limitations: Because of the low participation rate, low prevalence of subclinical thyroid dysfunction, and other unidentified recruitment biases, participants may not be representative of the elderly population.

Conclusions: After the confounding effects of comorbid conditions and use of medication were controlled for, subclinical thyroid dysfunction was not associated with depression, anxiety, or cognition.

Editors' Notes Context The relationship between subclinical thyroid dysfunction and disorders of cognition and mood is unclear. Contribution The authors studied 5868 general practice patients 65 years of age or older with a detailed medical history, thyroid tests, and standardized tests of cognition and mood. They found no association between subclinical thyroid dysfunction and anxiety, depression, or cognitive impairment in prediction models that adjusted for age, sex, social deprivation, medications, and comorbid diseases. Implications This study provides good evidence that subclinical thyroid dysfunction is not related to disorders of cognition and mood in older persons. —The Editors

 

Author and Article Information

From the University of Birmingham, Birmingham, United Kingdom.

Acknowledgments: The authors thank the practices and patients who participated in this study; the practice nurses and health care assistants who undertook the screening tests and saw patients on their behalf; and the staff of the Regional Endocrine Laboratory, University Hospital Birmingham National Health Service Foundation Trust. They also thank the other members of the Research Team and Steering Group: Mrs. Rhona Alekna (Research Nurse), Mrs. Pam Bridge (Project Officer), Mrs. Jacqui Cannon (Research Nurse), Dr. Michael Gammage (Cardiologist), Mr. Roger Holder (Statistician), Mrs. Elaine Kidney (Research Associate), Ms. Rose Nolan (Research Nurse), Mrs. Jo-Anne Miles (Research Nurse), Mrs. Val Redman (Senior Project Officer), Professor Michael Sheppard (Endocrinologist), Ms. Dawn Swancutt (Research Associate), and Mrs. Sally Warmington (Project Officer).

Grant Support: The study was funded by the Healthcare Foundation and received support from the Primary Care Research and Clinical Trials Unit and the Midlands GP Research Consortium. Sue Wilson was funded by a Department of Health Career Scientist Award. The Healthcare Foundation funded direct research, and the Primary Care Research and Clinical Trials Unit funded service support.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Lesley M. Roberts, PhD, Department of Primary Care and General Practice, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; e-mail, l.m.roberts{at}bham.ac.uk.

Current Author Addresses: Dr. Roberts, Professors Wilson, Hobbs, and Parle, and Mrs. Roalfe: Department of Primary Care and General Practice, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.

Dr. Pattison: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, United Kingdom.

Professor Franklyn: Department of Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.

Author Contributions: Conception and design: L.M. Roberts, H. Pattison, A. Roalfe, J. Franklyn, S. Wilson, F.D.R. Hobbs, J.V. Parle.

Analysis and interpretation of the data: L.M. Roberts, H. Pattison, A. Roalfe, J. Franklyn, S. Wilson, F.D.R. Hobbs, J.V. Parle.

Drafting of the article: L.M. Roberts, A. Roalfe.

Critical revision of the article for important intellectual content: L.M. Roberts, H. Pattison, A. Roalfe, J. Franklyn, S. Wilson, F.D.R. Hobbs, J.V. Parle.

Final approval of the article: L.M. Roberts, H. Pattison, A. Roalfe, J. Franklyn, S. Wilson, F.D.R. Hobbs, J.V. Parle.

Provision of study materials or patients: L.M. Roberts.

Statistical expertise: A. Roalfe.

Obtaining of funding: H. Pattison, A. Roalfe, J. Franklyn, S. Wilson, F.D.R. Hobbs, J.V. Parle.

Administrative, technical, or logistic support: L.M. Roberts, S. Wilson.

Collection and assembly of data: L.M. Roberts.

Read all Rapid Responses

Is there such a thing as Cognitive Disorder caused by Thyroid Malfunction?

Mladen M Davidovic, et al.

Annals Online, 27 Oct 2006 [Full text]

In Response

Gregory Goldenberg, et al.

Annals Online, 20 Dec 2006 [Full text]