Background Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Methods Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests. Results Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up. Conclusion We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.
References
[1]
Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, et al. (2004) Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 291: 228–238.
[2]
Bensenor IM, Lotufo PA, Menezes PR, Scazufca M (2010) Subclinical hyperthyroidism and dementia: the Sao Paulo Ageing & Health Study (SPAH). BMC Public Health 10: 298.
[3]
Ceresini G, Lauretani F, Maggio M, Ceda GP, Morganti S, et al. (2009) Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study. J Am Geriatr Soc 57: 89–93.
[4]
Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, et al. (2004) Thyroid status, disability and cognitive function, and survival in old age. JAMA 292: 2591–2599.
[5]
Hogervorst E, Huppert F, Matthews FE, Brayne C (2008) Thyroid function and cognitive decline in the MRC Cognitive Function and Ageing Study. Psychoneuroendocrinology 33: 1013–1022.
[6]
Kalmijn S, Mehta KM, Pols HA, Hofman A, Drexhage HA, et al. (2000) Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study. Clin Endocrinol (Oxf) 53: 733–737.
[7]
Roberts LM, Pattison H, Roalfe A, Franklyn J, Wilson S, et al. (2006) Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med 145: 573–581.
[8]
van Boxtel MP, Menheere PP, Bekers O, Hogervorst E, Jolles J (2004) Thyroid function, depressed mood, and cognitive performance in older individuals: the Maastricht Aging Study. Psychoneuroendocrinology 29: 891–898.
[9]
Casserly IP, Topol EJ (2004) Convergence of atherosclerosis and alzheimer's disease: Cholesterol, inflammation, and misfolded proteins. Discov Med 4: 149–156.
[10]
Luboshitzky R, Aviv A, Herer P, Lavie L (2002) Risk factors for cardiovascular disease in women with subclinical hypothyroidism. Thyroid 12: 421–425.
[11]
Stabouli S, Papakatsika S, Kotsis V (2010) Hypothyroidism and hypertension. Expert Rev Cardiovasc Ther 8: 1559–1565.
[12]
Hueston WJ, Pearson WS (2004) Subclinical hypothyroidism and the risk of hypercholesterolemia. Ann Fam Med 2: 351–355.
[13]
Kanaya AM, Harris F, Volpato S, Perez-Stable EJ, Harris T, et al. (2002) Association between thyroid dysfunction and total cholesterol level in an older biracial population: the health, aging and body composition study. Arch Intern Med 162: 773–779.
[14]
Walsh JP, Bremner AP, Bulsara MK, O'Leary P, Leedman PJ, et al. (2005) Thyroid dysfunction and serum lipids: a community-based study. Clin Endocrinol (Oxf) 63: 670–675.
[15]
Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, et al. (2006) Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 295: 1033–1041.
[16]
Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, et al. (2000) Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 132: 270–278.
[17]
Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, et al. (2010) Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 304: 1365–1374.
[18]
Auer J, Scheibner P, Mische T, Langsteger W, Eber O, et al. (2001) Subclinical hyperthyroidism as a risk factor for atrial fibrillation. Am Heart J 142: 838–842.
[19]
Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, et al. (1994) Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 331: 1249–1252.
[20]
Shepherd J, Blauw GJ, Murphy MB, Cobbe SM, Bollen EL, et al. (1999) The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk. Am J Cardiol 84: 1192–1197.
[21]
Trompet S, van Vliet P, de Craen AJ, Jolles J, Buckley BM, et al. (2010) Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol 257: 85–90.
[22]
Klein I, Danzi S (2007) Thyroid disease and the heart. Circulation 116: 1725–1735.
[23]
Nanchen D, Gussekloo J, Westendorp RG, Stott DJ, Jukema JW, et al. (2012) Subclinical Thyroid Dysfunction and the Risk of Heart Failure in Older Persons at High Cardiovascular Risk. J Clin Endocrinol Metab 97: 852–861.
[24]
Diez JJ, Iglesias P, Burman KD (2005) Spontaneous normalization of thyrotropin concentrations in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 90: 4124–4127.
[25]
Houx PJ, Shepherd J, Blauw GJ, Murphy MB, Ford I, et al. (2002) Testing cognitive function in elderly populations: the PROSPER study. PROspective Study of Pravastatin in the Elderly at Risk. J Neurol Neurosurg Psychiatry 73: 385–389.
[26]
Jorde R, Waterloo K, Storhaug H, Nyrnes A, Sundsfjord J, et al. (2006) Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment. J Clin Endocrinol Metab 91: 145–153.
[27]
Parle J, Roberts L, Wilson S, Pattison H, Roalfe A, et al. (2010) A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham Elderly Thyroid study. J Clin Endocrinol Metab 95: 3623–3632.
[28]
Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, et al. (2010) Guidelines for the management of atrial fibrillation: the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Europace 12: 1360–1420.
[29]
Ladenson PW, Singer PA, Ain KB, Bagchi N, Bigos ST, et al. (2000) American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med 160: 1573–1575.
[30]
Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, et al. (2007) Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol 14: e1–26.
[31]
Klubo-Gwiezdzinska J, Wartofsky L (2009) Thyrotropin blood levels, subclinical hypothyroidism, and the elderly patient. Arch Intern Med 169: 1949–1951.
[32]
Peeters RP (2009) Thyroid function and longevity: new insights into an old dilemma. J Clin Endocrinol Metab 94: 4658–4660.
[33]
Pinchera A (2005) Subclinical thyroid disease: to treat or not to treat? Thyroid 15: 1–2.
[34]
Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, et al. (1997) Total cholesterol and risk of mortality in the oldest old. Lancet 350: 1119–1123.
[35]
Packard CJ, Ford I, Robertson M, Shepherd J, Blauw GJ, et al. (2005) Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Circulation 112: 3058–3065.
[36]
van Bemmel T, Gussekloo J, Westendorp RG, Blauw GJ (2006) In a population-based prospective study, no association between high blood pressure and mortality after age 85 years. J Hypertens 24: 287–292.
[37]
Trompet S, Jukema JW, Katan MB, Blauw GJ, Sattar N, et al. (2009) Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study. Am J Epidemiol 170: 1415–1421.
[38]
Mooijaart SP, Sattar N, Trompet S, Polisecki E, de Craen AJ, et al. (2011) C-reactive protein and genetic variants and cognitive decline in old age: the PROSPER study. PLoS One 6: e23890.
