Skip to main content
American Journal of Alzheimer's Disease and Other Dementias logoLink to American Journal of Alzheimer's Disease and Other Dementias
. 2006 Jun-Jul;21(3):182–188. doi: 10.1177/1533317506289282

The Significance of Thyroid-Stimulating Hormone and Homocysteine in the Development of Alzheimer’s Disease in Mild Cognitive Impairment

A 6-Year Follow-up Study

Sylvia Annerbo 1, Lars-Olof Wahlund 2, Johan Lökk 3
PMCID: PMC10833276  PMID: 16869339

Abstract

Mild cognitive impairment (MCI) represents a transition between normal aging and Alzheimer’s disease (AD). The aim of this study was to investigate the predictive value of vitamin B12/folate, homocysteine, standard laboratory parameters, and concomitant diseases for development of AD in persons with an MCI diagnosis. Development of dementia was followed for 6 years in 93 consecutively recruited MCI persons. Information concerning the above factors was obtained from medical journals. Thirty-four percent of participants converted to AD within 6 years. A forward stepwise logistic regression was performed. The odds ratio (OR) for the Mini-Mental State Examination (MMSE) was 0.777; for age, 1.084; and for thyroid stimulating hormone (TSH), 0.287. The OR for homocysteine was 1.287 at 60 years of age and 1.087 at 65 years of age. Lower TSH levels together with the more established factors lower MMSE, higher homocysteine levels, and age were found to be predictive factors of AD. This may have clinical implications with regard to monitoring TSH levels and thyroxin substitution in MCI patients.

Keywords: MCI, Alzheimer’s disease, MMSE, homocysteine, TSH

Full Text

The Full Text of this article is available as a PDF (111.4 KB).

Contributor Information

Sylvia Annerbo, Geriatric Section, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care, Karolinska University Hospital, Stockholm, Sweden.

Lars-Olof Wahlund, Geriatric Section, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care, Karolinska University Hospital, Stockholm, Sweden.

Johan Lökk, Geriatric Section, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care, Karolinska University Hospital, Stockholm, Sweden, johan.lokk@karolinska.se .

References

  1. Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004;256:240-246. [DOI] [PubMed] [Google Scholar]
  2. Folstein MF, Folstein SE, McHugh PR. “Mini-Mental State”: a practical method for grading the cognitive stat of patients by the clinicians. J Psychiatry Res. 1975;12: 189-198. [DOI] [PubMed] [Google Scholar]
  3. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56: 303-308. [DOI] [PubMed] [Google Scholar]
  4. Wahlund LO, Pihlstrand E, Jonhagen ME. Mild cognitive impairment: experience from a memory clinic. Acta Neurol Scand Suppl. 2003;179:21-24. [PubMed] [Google Scholar]
  5. Morris JC. Dementia update 2003. Alzheimer Dis Assoc Disord. 2003;17:245-258. [DOI] [PubMed] [Google Scholar]
  6. Kivipelto M, Helkala EL, Laakso MP, et al. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ. 2001;332: 1447-1451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346:476-483. [DOI] [PubMed] [Google Scholar]
  8. Wang HX, Wahlin Å, Basun H, Fastborn J, Winblad B, Fratiglioni L. Vitamin B12 and folate in relation to the development of Alzheimer’s disease. Neurology. 2001;56: 1188-1194. [DOI] [PubMed] [Google Scholar]
  9. Lehmann M, Gottfries CG, Regland B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dement Geriatr Cogn Disord. 1999;10: 12-20. [DOI] [PubMed] [Google Scholar]
  10. Joosten E, Lesaffre E, Riezler R, et al. Is metabolic evidence for vitamin B12 and folate deficiency more frequent in elderly patients with Alzheimer’s disease? J Gerontol. 1997; 52A:76-79. [DOI] [PubMed] [Google Scholar]
  11. Björkegren K, Svärdsudd K. Serum cobalamin, folate, methylmalonic acid and total homocysteine as vitamin B12 and folate tissue deficiency markers amongst elderly Swedes: a population-based study. J Intern Med. 2001; 249:423-432. [DOI] [PubMed] [Google Scholar]
  12. Stryer L. Biochemistry. 4th ed. New York, NY: W. H. Freeman; 1995. [Google Scholar]
  13. Gottfries CG, Lehmann W, Regland B. Early diagnosis of cognitive impairment in the elderly with focus on Alzheimer’s disease. J Neural Transm. 1998;105:773-786. [DOI] [PubMed] [Google Scholar]
  14. van Osch LA, Hogervorst E, Combrinck M, Smith AD. Low thyroid-stimulating hormone as an independent risk factor for Alzheimer disease. Neurology. 2004;62: 1967-1971. [DOI] [PubMed] [Google Scholar]
  15. Volpato S, Guralnik JM, Fried LP, Remaley AT, Cappola AR, Launer LJ. Serum thyroxine level and cognitive decline in euthyroid older women. Neurology. 2002; 58:1055-1061. [DOI] [PubMed] [Google Scholar]
  16. Prinz PN, Scanlan JM, Vitaliano PP, et al. Thyroid hormones: positive relationships with cognition in healthy, euthyroid older men. J Gerontol A Biol Sci Med Sci. 1999; 54:M111-M116. [DOI] [PubMed] [Google Scholar]
  17. Kalmijn S, Metha KM, Pols HAP, Hofman A, Drexhage HA, Breteler MMB. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam Study. Clin Endocrinol (Oxf). 2000;53:733-737. [DOI] [PubMed] [Google Scholar]
  18. Colleran KM, Romero LR, Upton DA, Burge MR. Methimazole-induced hypothyroidism paradoxically decreases homocysteine. Metab Clin Exp. 2005;54: 460-465. [DOI] [PubMed] [Google Scholar]
  19. Gottfris CG, Winblad B. Dementia diseases in aging: several risk factors for Alzheimer’s disease. Lakartidningen. 1995;92:3017-3021. [PubMed] [Google Scholar]
  20. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Publ Health. 1998;88:1337-1342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Miller JW. Homocysteine and Alzheimer’s disease. Nutr Rev. 1999;57:126-129. [DOI] [PubMed] [Google Scholar]
  22. Hosmer DW Jr, Lemeshow S. Applied Logistic Regression. New York, NY: John Wiley & Sons; 1989. [Google Scholar]
  23. Lopez O, Huff FJ, Martinez AJ, Bedetti CD. Prevalence of thyroid abnormalities is not increased in Alzheimer’s disease. Neurobiol Aging. 1989;10:247-251. [DOI] [PubMed] [Google Scholar]
  24. Small GW, Matsuyama SS, Komanduri, R, Kumar V, Jarvik LF. Thyroid disease in patients with dementia of the Alzheimer type. J Am Geriatr Soc. 1985;33:538-539. [DOI] [PubMed] [Google Scholar]
  25. Luo L, Yano N, Mao Q, Jackson IM, Stopa EG. Thyrotrophic releasing hormone (TRH) in the hippocampus of Alzheimer patients. J Alzheimers Dis. 2002; 4:97-103. [DOI] [PubMed] [Google Scholar]
  26. Perry EK. The cholinergic system in old age and Alzheimer’s disease. Age Aging. 1980;9:1-8. [DOI] [PubMed] [Google Scholar]
  27. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam study. Ann Intern Med. 2000;132:270-278. [DOI] [PubMed] [Google Scholar]
  28. Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med. 2002;137:904-914. [DOI] [PubMed] [Google Scholar]
  29. Morris MS, Bostom AG, Jacques PF, Selhub J, Rosenberg IH. Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in the Third US National Health and Nutrition Examination Survey. Atherosclerosis. 2001;155: 195-200. [DOI] [PubMed] [Google Scholar]
  30. Breteler MMB. Vascular risk for Alzheimer’s disease: an epidemiologic perspective. Neurobiol Aging. 2000;21:153-160. [DOI] [PubMed] [Google Scholar]
  31. Daly E, Zaitchik D, Touchon J, et al. Predicting conversion to Alzheimer disease using standardized clinical information. Arch Neurol. 2000;57:675-680. [DOI] [PubMed] [Google Scholar]
  32. Bennett DA, Wilson RS, Schneider JA, et al. Natural history of mild cognitive impairment in a population-based prospective cohort. Neurology. 2002;59:198-205. [DOI] [PubMed] [Google Scholar]
  33. Bowen J, Teri L, Kukull W, McCormick W, McCurry SM, Larson EB. Progression to dementia in patients with isolated memory loss. Lancet. 1997;349:763-765. [DOI] [PubMed] [Google Scholar]
  34. Sawin CT. Age-related changes in thyroid function. In: Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000: 254-256. [Google Scholar]

Articles from American Journal of Alzheimer's Disease and Other Dementias are provided here courtesy of SAGE Publications

RESOURCES