Low thyroid-stimulating hormone as an independent risk factor for Alzheimer disease
Abstract
OBJECTIVE: To assess a possible relationship between thyroid-stimulating hormone (TSH) levels, vascular risk factors, and Alzheimer disease (AD). METHODS: TSH levels were measured in 178 AD patients (35 confirmed post mortem) and 291 cognitively screened control subjects who were all euthyroid (TSH: 0.5 to 6 mU/L). The risk of AD was determined in participants with lower levels of TSH, several cerebrovascular risk factors, and other potential confounds. RESULTS: AD patients had significantly lower levels of TSH than control subjects. Lowered TSH was associated with a more than twofold increased risk of AD (odds ratio = 2.36, 95% CI = 1.19 to 4.67), independent of other risk factors. CONCLUSION: Lowered TSH within the normal range is a risk factor for AD, independent of several cerebrovascular risk factors and confounding variables.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Kivipelto, M., Helkala, E.-L., Laakso, M. P., Hänninen, T., Hallikainen, M., Alhainen, K., Soininen, H., Tuomilehto, J., & Nissinen, A. (2001) · BMJ · doi:10.1136/bmj.322.7300.1447 · Cited by 1,618 · see citing works
Hak, A. E., Pols, H. A. P., Visser, T. J., Drexhage, H. A., Hofman, A., & Witteman, J. C. M. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-132-4-200002150-00004 · Cited by 1,336 · see citing works
Apolipoprotein E genotyping by one-stage PCR
Wenham, P. R., Price, W. H., & Blundell, G. (1991) · The Lancet · doi:10.1016/0140-6736(91)92823-k · Cited by 1,070 · see citing works
Total homocysteine in plasma or serum: methods and clinical applications
Ueland, P. M., Refsum, H., Stabler, S. P., Malinow, M. R., Andersson, A. D. R., & Allen, R. H. (1993) · Clinical Chemistry · doi:10.1093/clinchem/39.9.1764 · Cited by 984 · see citing works
Vascular risk factors for Alzheimer’s disease:
Breteler, M. M. B. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00110-4 · Cited by 664 · see citing works
History of Depression as a Risk Factor for Dementia: An Updated Review
Jorm, A. F. (2001) · Australian & New Zealand Journal of Psychiatry · doi:10.1046/j.1440-1614.2001.00967.x · Cited by 526 · see citing works
Effects of Subclinical Thyroid Dysfunction on the Heart
Biondi, B., Palmieri, E. A., Lombardi, G., & Fazio, S. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-11-200212030-00011 · Cited by 443 · see citing works
Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study
Kalmijn, S., Mehta, K. M., Pols, H. A. P., Albert Hofman, D., Drexhage, H. A., & Breteler, M. M. B. (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01146.x · Cited by 319 · see citing works
Subclinical hyperthyroidism as a risk factor for atrial fibrillation
Auer, J., Scheibner, P., Mische, T., Langsteger, W., Eber, O., & Eber, B. (2001) · American Heart Journal · doi:10.1067/mhj.2001.119370 · Cited by 314 · see citing works
THE CHOLINERGIC SYSTEM IN OLD AGE AND ALZHEIMER'S DISEASE
Perry, E. K. (1980) · Age and Ageing · doi:10.1093/ageing/9.1.1 · Cited by 248 · see citing works
Morris, M. S., Bostom, A. G., Jacques, P. F., Selhub, J., & Rosenberg, I. H. (2001) · Atherosclerosis · doi:10.1016/s0021-9150(00)00537-2 · Cited by 134 · see citing works
Association between dementia and elevated TSH: A community-based study
Ganguli, M., Burmeister, L. A., Seaberg, E. C., Belle, S. H., & DeKosky, S. T. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00489-0 · Cited by 131 · see citing works
Serum thyroxine level and cognitive decline in euthyroid older women
Volpato, S., Guralnik, J. M., Fried, L. P., Remaley, A. T., Cappola, A. R., & Launer, L. J. (2002) · Neurology · doi:10.1212/wnl.58.7.1055 · Cited by 124 · see citing works
Toft, A. D., & Boon, N. A. (2000) · Heart · doi:10.1136/heart.84.4.455 · Cited by 122 · see citing works
Oxidative Stress and Anti-Oxidant Metabolites in Patients with Hyperthyroidism: Effect of Treatement
Bianchi, G., Solaroli, E., Zaccheroni, V., Grossi, G., Bargossi, A., Melchionda, N., & Marchesini, G. (1999) · Hormone and Metabolic Research · doi:10.1055/s-2007-978808 · Cited by 114 · see citing works
Evaluation of Novel Assays in Clinical Chemistry: Quantification of Plasma Total Homocysteine
Nexø, E., Engbaek, F., Ueland, P. M., et al. (2000) · Clinical Chemistry · doi:10.1093/clinchem/46.8.1150 · Cited by 94 · see citing works
Depression and Anxiety in Hyperthyroidism
Demet, M. M., Özmen, B., Deveci, A., Boyvada, S., Adıgüzel, H., & Aydemır, Ö. (2002) · Archives of Medical Research · doi:10.1016/s0188-4409(02)00410-1 · Cited by 93 · see citing works
Giovannini, M. G., Casamenti, F., Nistri, A., Paoli, F., & Pepeu, G. (1991) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1991.tb12179.x · Cited by 86 · see citing works
Hyperthyroidism and Cardiovascular Morbidity and Mortality
Osman, F., GAMMAGE, M. D., & Franklyn, J. A. (2002) · Thyroid · doi:10.1089/105072502760143854 · Cited by 74 · see citing works
Thyroid Hormones: Positive Relationships With Cognition in Healthy, Euthyroid Older Men
Prinz, P. N., Scanlan, J. M., VITALIANO, P. P., Moe, K. E., Soo Borson, B., Toivola, B., Merriam, G. R., Larsen, L. H., & Reed, H. L. (1999) · The Journals of Gerontology Series A · doi:10.1093/gerona/54.3.m111 · Cited by 74 · see citing works
Thyrotropin releasing hormone (TRH) in the hippocampus of Alzheimer patients
Luo, L., Yano, N., Mao, Q., JACKSON, I. M. D., & Stopa, E. G. (2002) · Journal of Alzheimer s Disease · doi:10.3233/jad-2002-4204 · Cited by 63 · see citing works
Hogervorst, E., Barnetson, L. P. D., Jobst, K. A., Nagy, Z., Combrinck, M. I., & Smith, A. D. (2000) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017222 · Cited by 55 · see citing works
Self-citationCharacteristic Plasma Hormone Changes in Alzheimer's Disease
CHRISTIE, J. E., Whalley, L. J., Bennie, J., Dick, H., Blackburn, I. M., Blackwood, D., & Fink, G. (1987) · The British Journal of Psychiatry · doi:10.1192/bjp.150.5.674 · Cited by 54 · see citing works
Endocrine Modulators of Necrotic Neuron Death
Chan, R. S., Huey, E. D., Maecker, H. L., Cortopassi, K. M., Howard, S. A., Iyer, A., Mclntosh, L. J., Ajilore, O., Brooke, S. M., & Sapolsky, R. M. (1996) · Brain Pathology · doi:10.1111/j.1750-3639.1996.tb00877.x · Cited by 39 · see citing works
Thyroid Disease in Patients With Dementia of the Alzheimer Type
Small, G. W., Matsuyama, S. S., Komanduri, R., Kumar, V., & Jarvik, L. F. (1985) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1985.tb04617.x · Cited by 37 · see citing works
NS-3, a TRH-analog, reverses memory disruption by stimulating cholinergic and noradrenergic systems
Ogasawara, T., Itoh, Y., Tamura, M., Ukai, Y., Yoshikuni, Y., & Kimura, K. (1996) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)02039-x · Cited by 28 · see citing works
Depressive Symptoms in Hypothyroid Disorder with some Observations on Biochemical Correlates
Gunnarsson, T., Sjöberg, S., Eriksson, M., et al. (2001) · Neuropsychobiology · doi:10.1159/000054869 · Cited by 24 · see citing works
Prevalence of thyroid abnormalities is not increased in Alzheimer's disease
López, O. L., Huff, F. J., Martinez, A. J., et al. (1989) · Neurobiology of Aging · doi:10.1016/0197-4580(89)90058-4 · Cited by 23 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [9]9. Hogervorst E, Combrinck M, Smith AD. Low thyroid stimulating hormone in cases with dementia. Neurobiol Aging 2002;23:1128. 1970 NEUROLOGY 62 June (1 of 2) 2004
- [19]19. Roth M, Huppert FA, Tym E, Mountjoy CQ. CAMDEX: the Cambridge Examination for Mental Disorders of the Elderly. Cambridge, UK: Cambridge University Press, 1988.
- [33]33. Bianchi G, Solaroli E, Zaccheroni V, et al. Oxidative stress and antioxidant metabolites in patients with hyperthyroidism: effect of treatment. Horm Metab Res 1999;31:620-624.
Cited by
Sorted by citations
The Clinical Significance of Subclinical Thyroid Dysfunction
Biondi, B., & Cooper, D. S. (2008) · Endocrine Reviews · doi:10.1210/er.2006-0043 · Cited by 1,418 · see citing works
Cooper, D. S., & Biondi, B. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60276-6 · Cited by 1,039 · see citing works
Biondi, B., Bartalena, L., Cooper, D. S., Hegedüs, L., Laurberg, P., & Kahaly, G. J. (2015) · European Thyroid Journal · doi:10.1159/000438750 · Cited by 323 · see citing works
Tan, Z. S. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.14.1514 · Cited by 225 · see citing works
Thyroid Hormones, Dementia, and Atrophy of the Medial Temporal Lobe
de Jong, F. J., den Heijer, T., Visser, T. J., de Rijke, Y. B., Drexhage, H. A., Hofman, A., & Breteler, M. M. B. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0449 · Cited by 129 · see citing works
The Thyroid in Mind: Cognitive Function and Low Thyrotropin in Older People
Gan, E. H., & Pearce, S. H. S. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2284 · Cited by 93 · see citing works
Papi, G., Pearce, E. N., Braverman, L. E., Betterle, C., & Roti, E. (2005) · The American Journal of Medicine · doi:10.1016/j.amjmed.2005.01.004 · Cited by 39 · see citing works
Sonic hedgehog signalling pathway contributes in age-related disorders and Alzheimer’s disease
Parashar, A., jha, D., Mehta, V., Chauhan, B., Ghosh, P., Deb, P. K., Jaiswal, M., & Prajapati, S. K. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102271 · Cited by 28 · see citing works
Du Puy, R. S., Poortvliet, R. K. E., Mooijaart, S. P., den Elzen, W. P. J., Jagger, C., Pearce, S. H. S., Arai, Y., Hirose, N., Teh, R., Menzies, O., et al. (2021) · Thyroid® · doi:10.1089/thy.2020.0567 · Cited by 27 · see citing works
- Authors
- van Osch, L. A. D. M., Hogervorst, E., Combrinck, M., & Smith, A. D.
- Affiliations
- From the Oxford Project to Investigate Memory and Ageing, Department of Pharmacology, University of Oxford and Radcliffe Infirmary, UK.
- University of Oxford (GB)
- Venue
- Neurology
- Published
- 2004-06-08
- Volume
- 62
- Issue
- 11
- Pages
- 1967-1971
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2019247935
- Cited by
- 146
- References
- 31
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 9 · 2023: 8 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 3 · 2018: 4 · 2017: 11 · 2016: 9 · 2015: 8 · 2014: 3 · 2013: 13 · 2012: 7
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- thyroid-stimulating hormone, Alzheimer's disease, risk factors, cerebrovascular risk factors, hypothyroidism, euthyroidism, thyroid function, cognitive decline
- MeSH terms
- Aged, Aged, 80 and over, Alcohol Drinking, Alzheimer Disease, Apolipoproteins E, Creatinine, Diabetes Mellitus, England, Female, Follow-Up Studies, Homocysteine, Humans, Hypertension, Male, Reference Values, Risk Factors, Serum Albumin, Smoking, Thyrotropin, Thyroxine, Cohort Studies, Comorbidity, Odds Ratio
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
