Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer's Disease
Sudha Seshadri, M.D., Alexa Beiser, Ph.D., Jacob Selhub, Ph.D., Paul F. Jacques, Sc.D., Irwin H. Rosenberg, M.D., Ralph B. D'Agostino, Ph.D., Peter W.F. Wilson, M.D., and Philip A. Wolf, M.D.
Methods A total of 1092 subjects without dementia (667 womenand 425 men; mean age, 76 years) from the Framingham Study constitutedour study sample. We examined the relation of the plasma totalhomocysteine level measured at base line and that measured eightyears earlier to the risk of newly diagnosed dementia on follow-up.We used multivariable proportional-hazards regression to adjustfor age, sex, apolipoprotein E genotype, vascular risk factorsother than homocysteine, and plasma levels of folate and vitaminsB12 and B6.
Results Over a median follow-up period of eight years, dementiadeveloped in 111 subjects, including 83 given a diagnosis ofAlzheimer's disease. The multivariable-adjusted relative riskof dementia was 1.4 (95 percent confidence interval, 1.1 to1.9) for each increase of 1 SD in the log-transformed homocysteinevalue either at base line or eight years earlier. The relativerisk of Alzheimer's disease was 1.8 (95 percent confidence interval,1.3 to 2.5) per increase of 1 SD at base line and 1.6 (95 percentconfidence interval, 1.2 to 2.1) per increase of 1 SD eightyears before base line. With a plasma homocysteine level greaterthan 14 µmol per liter, the risk of Alzheimer's diseasenearly doubled.
From the Department of Neurology (S.S., P.A.W.) and the Department of Medicine (P.W.F.W.), Boston University School of Medicine; the Department of Epidemiology and Biostatistics, Boston University School of Public Health (A.B.); the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University (J.S., P.F.J., I.H.R.); and the Department of Mathematics and Statistics, Boston University (R.B.D.) — all in Boston.
Address reprint requests to Dr. Wolf at the Department of Neurology (Neurological Epidemiology and Genetics), Boston University School of Medicine, 715 Albany St., B-608, Boston, MA 02118-2526, or at pawolf{at}bu.edu.
Homocysteine and Dementia
Shea T. B., Rogers E., Auer J., Berent R., Eber B., Seshadri S., Wolf P. A.
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N Engl J Med 2002;
346:2007-2008, Jun 20, 2002.
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