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

Lesley M. Roberts, PhD; Helen Pattison, PhD; Andrea Roalfe, MSc; Jayne Franklyn, MD, PhD; Sue Wilson, PhD; F.D. Richard Hobbs, MB ChB; and James V. Parle, MD
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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@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.

Ann Intern Med. 2006;145(8):573-581. doi:10.7326/0003-4819-145-8-200610170-00006
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Thyroid dysfunction, cognitive dysfunction, and depression are all common problems among elderly persons, and the possibility that thyroid dysfunction might be a causal factor in cognitive dysfunction and depression is important, particularly because treatment of thyroid dysfunction is relatively straightforward. Previous reports of associations between these conditions have been conflicting, and a systematic review of the literature was inconclusive (1). The conflicting findings of previous studies may be attributable to various factors, such as small sample size, selection or inclusion criteria, and differing definitions of subclinical dysfunction, but may also be due in part to lack of control for potential confounding variables, such as comorbid conditions and medication use. Our findings derive from a large community-based sample (5868 patients ≥65 years of age who were recruited from 20 primary care practices) and are based on standard laboratory reference ranges. Evidence is robust that for patients without clinically determined disease, no clinically relevant association exists between thyroid function and cognitive function, anxiety, or depression.

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Grahic Jump Location
Appendix Figure.
Recruitment flow chart.

HADS = Hospital Anxiety and Depression Scale; MEAMS = Middlesex Elderly Assessment of Mental State; MMSE = Mini-Mental State Examination.

Grahic Jump Location




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Is there such a thing as Cognitive Disorder caused by Thyroid Malfunction?
Posted on October 27, 2006
Mladen M Davidovic
Geriatric Clinic
Conflict of Interest: None Declared

Reversible cognitive deficit is classically tied up with known cases from our practices of unknown diseases of the thyroid. On the other hand, if we conclude that clinical hypothyroidism correlate clearly with the level of possible cognitive deficit ,the situation regarding subclinical hypothyroidism is still a controversial issue.


Jellinek EH 1962[1 ]

Fits, faints, coma and dementia myxoedema Tonks CM 1964[2 ]

Mental illnesses in hypothyroid patients Whybrow PC 1969[3 ]

Mental changes accompanying thyroid gland dysfunction Olivarius BDF 1970[4 ]

Reversible psychosis and dementia in myxedema


If we look at recent studies the conclusion will be the same .There is a lot of different data. Basic problem is that we don,t search the possible cause of potentially reversible cognitive disorder (5,6) ,but on the other hand there is only a small possibility that we will find curative cause of cognitive deficit(7). The influence of thyroid function on cognitive capacity is much more understanding. Subclinical hypothyroidism is generally linked to different changes of cognitive funtion,mood disorders and other depressive or anxiety symptoms. Specially in the old people.(8) For example: Baseline neuropsychological performance was within the normal range, while an age-dependent reduction was found in attentive function. After L-thyroxine treatment, an increase in serum fT4 was detected in parallel with thyroid stimulating hormone (TSH) reduction. Verbal fluency and depression scores showed a slight improvement. A positive correlation was found between TSH reduction and improved mood scores.(9). There is also a corellation between the level of FT4 concentrations and self-reported feelings of fear and fatigue even in euthyroid patient with Alzheimer dementia.(10).


1. Jellinek EH. 1962- Fits, faints, coma and dementia myxoedema. Lancet, 2: 1010-1012. 2. Tonks CM. 1964- Mental illnesses in hypothyroid patients. British Journal of Psychiatry; 110: 706-710.

3. Whybrow PC, Prange AJ, Treadway CR.1969-Mental changes accompanying thyroid gland dysfunction. Archives of General Psychiatry; 20: 48-63

4. Olivarius BDF, Roder E. 1970-Reversible psychosis and dementia in myxedema. Acta Psychiatrica Scandinavica; 46: 1-13.

5. Hejl A, Hogh P, Waldemar G. 2002-Potentially reversible conditions in 1000 consecutive memory clinic patients.- J Neurol Neurosurg Psychiatry. ;73(4):390-4.

6. Lopponen M, Raiha I, Isoaho R, Vahlberg T, Kivela SL. 2003- Diagnosing cognitive impairment and dementia in primary health care - a more active approach is needed.- Age Ageing. ;32(6):606-12.

7. Ovsiew F. 2003-Seeking reversibility and treatability in dementia. - Semin Clin Neuropsychiatry. ;8(1):3-11.

8. Davis JD, Stern RA, Flashman LA (2003 )-Cognitive and neuropsychiatric aspects of subclinical hypothyroidism: significance in the elderly. Curr Psychiatry Rep. ;5(5):384-90 9. Bono G, Fancellu R, Blandini F, Santoro G, Mauri M.( 2004)-Cognitive and affective status in mild hypothyroidism and interactions with L- thyroxine treatment. Acta Neurol Scand. ;110(1):59-66.

10.Stern R. A.; Davis J. D. , Rogers B. L. ; Smith K. E. R. Harrington C. J. ,; Ott B. R. ; Jackson I.M. D. , Prange A. J. 2004- Preliminary Study of the Relationship Between Thyroid Status and Cognitive and Neuropsychiatric Functioning in Euthyroid Patients with Alzheimer dementia. - Cognitive & Behavioral Neurology. , ,17(4):219-223.

11. Annewieke W. van den Beld, Theo J. Visser, Richard A. Feelders, Diederick E. Grobbee, and Steven W. J. Lamberts 2005-Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Men-J Clin Endocrinol Metab; 90: 6403-6409

12. Roberts L. M., Pattison H., Roalfe A., and all. - Is Subclinical Thyroid Dysfunction in the Elderly Associated with Depression or Cognitive Dysfunction? - Ann of Int. Med. 2006 ,145/ 8: 573-581

Conflict of Interest:

None declared

In Response
Posted on December 20, 2006
Gregory Goldenberg
New York Methodist
Conflict of Interest: None Declared

In reference to the article "Is Subclinical Thyroid Dysfunction in the Elderly Associated with Depression or Cognitive Dysfunction?" by Lesley M. Roberts et. al. published in the last issue of Annals. The article addresses a clinically relevant and interesting issue. A cross- sectional study explores a possible relationship between subclinical thyroid dysfunction and mood/cognition in elderly people. It is reasonable to expect mild or early cognitive dysfunction, if such exists, related to subclinical thyroid dysfunction. However, the traditional Mini -Mental Status Examination (MMSE) is not sensitive to mild and early cognitive dysfunction and seems to be inappropriate for the task of the study. The other screening tool, Middlesex Elderly Assessment of Mental State (MEAMS), "was developed as a screeing test to detect gross impairment of specific cognitive skills in elderly persons" (p. 574). The sensitivity of this scale to mild and early cognitive impairment is not clear and is not presented well by authors. Therefore, cognitive scales used in the study may not be adequate in answering this interesting question on the relationship between subclinical thyroid dysfunction and cognitive impairment in elderly persons.

Conflict of Interest:

None declared

Submit a Comment/Letter

Summary for Patients

Mild Thyroid Dysfunction Is Not Associated with Anxiety, Depression, or Cognition in the Elderly

The summary below is from the full report titled “Is Subclinical Thyroid Dysfunction in the Elderly Associated with Depression or Cognitive Dysfunction?” It is in the 17 October 2006 issue of Annals of Internal Medicine (volume 145, pages 573-581). The authors are L.M. Roberts, H. Pattison, A. Roalfe, J. Franklyn, S. Wilson, F.D.R. Hobbs, and J.V. Parle.


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