This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McIlroy, S. P. Articles by Passmore, A. P. Search for Related Content PubMed PubMed Citation Articles by McIlroy, S. P. Articles by Passmore, A. P. Related Collections Behavioral Changes and Stroke Brain Circulation and Metabolism Genetics of Stroke Risk Factors for Stroke

(Stroke. 2002;33:2351.)
© 2002 American Heart Association, Inc.

Original Contributions

Moderately Elevated Plasma Homocysteine, Methylenetetrahydrofolate Reductase Genotype, and Risk for Stroke, Vascular Dementia, and Alzheimer Disease in Northern Ireland

Stephen P. McIlroy, PhD; Kevin B. Dynan, MD; John T. Lawson, FRCR; Christopher C. Patterson, PhD A. Peter Passmore, MD

From the Departments of Geriatric Medicine (S.P.M., K.B.D., A.P.P.) and Epidemiology and Public Health (C.C.P), Queen’s University Belfast, and Department of Radiology, Belfast City Hospital Trust Group (J.T.L.), Belfast, Northern Ireland.

Correspondence to Dr S.P. McIlroy, Department of Geriatric Medicine, Queen’s University Belfast, Whitla Medical Building, 97 Lisburn Rd, Belfast BT9 7BL, Northern Ireland. E-mail s.mcilroy{at}qub.ac.uk

Background and Purpose— Elevated plasma homocysteine level has been associated with increased risk for cardiovascular and cerebrovascular disease. Variation in the levels of this amino acid has been shown to be due to nutritional status and methylenetetrahydrofolate reductase (MTHFR) genotype.

Methods— Under a case-control design we compared fasting levels of homocysteine and MTHFR genotypes in groups of subjects consisting of stroke, vascular dementia (VaD), and Alzheimer disease patients and normal controls from Northern Ireland.

Results— A significant increase in plasma homocysteine was observed in all 3 disease groups compared with controls. This remained significant after allowance for confounding factors (age, sex, hypertension, cholesterol, smoking, creatinine, and nutritional measures). MTHFR genotype was not found to influence homocysteine levels, although the T allele was found to increase risk for VaD and perhaps dementia after stroke.

Conclusions— We report that moderately high plasma levels of homocysteine are associated with stroke, VaD, and Alzheimer disease. This is not due to vascular risk factors, nutritional status, or MTHFR genotype.

Key Words: cerebrovascular disorders • dementia • genetics • homocyst(e)ine

This article has been cited by other articles:

				N. Purandare Preventing dementia: role of vascular risk factors and cerebral emboli Br. Med. Bull., September 1, 2009; 91(1): 49 - 59. [Abstract] [Full Text] [PDF]

				C. Wagner and M. J Koury S-Adenosylhomocysteine a better indicator of vascular disease than homocysteine? Am. J. Clinical Nutrition, December 1, 2007; 86(6): 1581 - 1585. [Abstract] [Full Text] [PDF]

				J. L. Cummings, R. Doody, and C. Clark Disease-modifying therapies for Alzheimer disease: Challenges to early intervention Neurology, October 16, 2007; 69(16): 1622 - 1634. [Abstract] [Full Text] [PDF]

				E. N. Rowan, H. O. Dickinson, S. Stephens, C. Ballard, R. Kalaria, and R. Anne Kenny Homocysteine and post-stroke cognitive decline Age Ageing, May 1, 2007; 36(3): 339 - 343. [Full Text] [PDF]

				L. Hao, J. Ma, J. Zhu, M. J. Stampfer, Y. Tian, W. C. Willett, and Z. Li High Prevalence of Hyperhomocysteinemia in Chinese Adults Is Associated with Low Folate, Vitamin B-12, and Vitamin B-6 Status J. Nutr., February 1, 2007; 137(2): 407 - 413. [Abstract] [Full Text] [PDF]

				I. J. Kullo, K. Ding, E. Boerwinkle, S. T. Turner, T. H. Mosley Jr, S. L.R. Kardia, and M. de Andrade Novel Genomic Loci Influencing Plasma Homocysteine Levels Stroke, July 1, 2006; 37(7): 1703 - 1709. [Abstract] [Full Text] [PDF]

				E. Cho, S. H Zeisel, P. Jacques, J. Selhub, L. Dougherty, G. A Colditz, and W. C Willett Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am. J. Clinical Nutrition, April 1, 2006; 83(4): 905 - 911. [Abstract] [Full Text] [PDF]

				H.-K. Kuo, F. A. Sorond, J.-H. Chen, A. Hashmi, W. P. Milberg, and L. A. Lipsitz The Role of Homocysteine in Multisystem Age-Related Problems: A Systematic Review J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2005; 60(9): 1190 - 1201. [Abstract] [Full Text] [PDF]

				M. Kurella, G. M. Chertow, L. F. Fried, S. R. Cummings, T. Harris, E. Simonsick, S. Satterfield, H. Ayonayon, and K. Yaffe Chronic Kidney Disease and Cognitive Impairment in the Elderly: The Health, Aging, and Body Composition Study J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2127 - 2133. [Abstract] [Full Text] [PDF]

				S. Cronin, K. L. Furie, and P. J. Kelly Dose-Related Association of MTHFR 677T Allele With Risk of Ischemic Stroke: Evidence From a Cumulative Meta-Analysis Stroke, July 1, 2005; 36(7): 1581 - 1587. [Abstract] [Full Text] [PDF]

				S. L. Cole, A. Grudzien, I. O. Manhart, B. L. Kelly, H. Oakley, and R. Vassar Statins Cause Intracellular Accumulation of Amyloid Precursor Protein, {beta}-Secretase-cleaved Fragments, and Amyloid {beta}-Peptide via an Isoprenoid-dependent Mechanism J. Biol. Chem., May 13, 2005; 280(19): 18755 - 18770. [Abstract] [Full Text] [PDF]

				N. Purandare, C. Ballard, and A. Burns Preventing dementia Adv. Psychiatr. Treat., May 1, 2005; 11(3): 176 - 183. [Abstract] [Full Text] [PDF]

				C. B. Kelly, A. P. McDonnell, T. G. Johnston, C. Mulholland, S. J. Cooper, D. McMaster, A. Evans, and A. S. Whitehead The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland J Psychopharmacol, December 1, 2004; 18(4): 567 - 571. [Abstract] [PDF]

				J. P. Casas, A. D. Hingorani, L. E. Bautista, and P. Sharma Meta-analysis of Genetic Studies in Ischemic Stroke: Thirty-two Genes Involving Approximately 18 000 Cases and 58 000 Controls Arch Neurol, November 1, 2004; 61(11): 1652 - 1661. [Abstract] [Full Text] [PDF]

				A. Garcia and K. Zanibbi Homocysteine and cognitive function in elderly people Can. Med. Assoc. J., October 12, 2004; 171(8): 897 - 904. [Abstract] [Full Text] [PDF]

				P. Quadri, C. Fragiacomo, R. Pezzati, E. Zanda, G. Forloni, M. Tettamanti, and U. Lucca Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia Am. J. Clinical Nutrition, July 1, 2004; 80(1): 114 - 122. [Abstract] [Full Text] [PDF]

				J. D. Spence Preventing Dementia by Treating Hypertension and Preventing Stroke Hypertension, July 1, 2004; 44(1): 20 - 21. [Full Text] [PDF]

				F. M. Faraci and S. R. Lentz Hyperhomocysteinemia, Oxidative Stress, and Cerebral Vascular Dysfunction Stroke, February 1, 2004; 35(2): 345 - 347. [Full Text] [PDF]

				K. Schroecksnadel, B. Frick, D. Fuchs, S. P. McIlroy, and A. P. Passmore Immune Activation to Underlie Moderate Hyperhomocysteinemia in Stroke and Dementia? Stroke, April 1, 2003; 34(4): 833 - 844. [Full Text] [PDF]