BACKGROUND: Impaired antioxidant defenses are implicated in neurodegenerative disease. The plasma levels of urate, a water-soluble antioxidant, are reduced in Alzheimer's disease (AD). OBJECTIVE: We aimed to test the hypotheses that high plasma urate at baseline is associated with: (1) a reduced rate of conversion from mild cognitive impairment (MCI) to AD and (2) a lower rate of cognitive decline in MCI. METHODS:Plasma urate was obtained at baseline from 747 participants in a 3-year, randomized, double-blind, placebo-controlled study of donepezil, vitamin E or placebo for delaying the progression of MCI to AD.The association between baseline urate and conversion from MCI to AD was examined by Cox proportional hazards regression. The relationship between baseline urate and cognitive change on the cognitive subscale of the Alzheimer's Disease Assessment Scale was evaluated by longitudinal analysis. RESULTS:Baseline plasma urate was not associated with the rate of conversion of MCI to AD. In the placebo arm, high plasma urate was related to a slower rate of cognitive decline over 3 years, although this was not reproduced in the other treatment arms. CONCLUSION: While plasma urate levels did not predict the progression of MCI to AD, high urate may be associated with a reduced rate of cognitive decline in MCI patients not treated with donepezil or vitamin E. The results support the investigation of biomarkers of antioxidant status as risk factors for cognitive decline in MCI. Copyright 2008 S. Karger AG, Basel.
RCT Entities:
BACKGROUND: Impaired antioxidant defenses are implicated in neurodegenerative disease. The plasma levels of urate, a water-soluble antioxidant, are reduced in Alzheimer's disease (AD). OBJECTIVE: We aimed to test the hypotheses that high plasma urate at baseline is associated with: (1) a reduced rate of conversion from mild cognitive impairment (MCI) to AD and (2) a lower rate of cognitive decline in MCI. METHODS: Plasma urate was obtained at baseline from 747 participants in a 3-year, randomized, double-blind, placebo-controlled study of donepezil, vitamin E or placebo for delaying the progression of MCI to AD.The association between baseline urate and conversion from MCI to AD was examined by Cox proportional hazards regression. The relationship between baseline urate and cognitive change on the cognitive subscale of the Alzheimer's Disease Assessment Scale was evaluated by longitudinal analysis. RESULTS: Baseline plasma urate was not associated with the rate of conversion of MCI to AD. In the placebo arm, high plasma urate was related to a slower rate of cognitive decline over 3 years, although this was not reproduced in the other treatment arms. CONCLUSION: While plasma urate levels did not predict the progression of MCI to AD, high urate may be associated with a reduced rate of cognitive decline in MCI patients not treated with donepezil or vitamin E. The results support the investigation of biomarkers of antioxidant status as risk factors for cognitive decline in MCI. Copyright 2008 S. Karger AG, Basel.
Authors: D A Evans; H H Funkenstein; M S Albert; P A Scherr; N R Cook; M J Chown; L E Hebert; C H Hennekens; J O Taylor Journal: JAMA Date: 1989-11-10 Impact factor: 56.272
Authors: M Cristina Polidori; Paola Mattioli; Sarah Aldred; Roberta Cecchetti; Wilhelm Stahl; Helen Griffiths; Umberto Senin; Helmut Sies; Patrizia Mecocci Journal: Dement Geriatr Cogn Disord Date: 2004-07-29 Impact factor: 2.959
Authors: Michael A Schwarzschild; Steven R Schwid; Kenneth Marek; Arthur Watts; Anthony E Lang; David Oakes; Ira Shoulson; Alberto Ascherio; Christopher Hyson; Emily Gorbold; Alice Rudolph; Karl Kieburtz; Stanley Fahn; Lisa Gauger; Christopher Goetz; John Seibyl; Misser Forrest; John Ondrasik Journal: Arch Neurol Date: 2008-04-14
Authors: P Rinaldi; M C Polidori; A Metastasio; E Mariani; P Mattioli; A Cherubini; M Catani; R Cecchetti; U Senin; P Mecocci Journal: Neurobiol Aging Date: 2003-11 Impact factor: 4.673
Authors: D J Schretlen; A B Inscore; T D Vannorsdall; M Kraut; G D Pearlson; B Gordon; H A Jinnah Journal: Neurology Date: 2007-10-02 Impact factor: 9.910
Authors: Xiqun Chen; Thomas C Burdett; Cody A Desjardins; Robert Logan; Sara Cipriani; Yuehang Xu; Michael A Schwarzschild Journal: Proc Natl Acad Sci U S A Date: 2012-12-17 Impact factor: 11.205
Authors: Alberto Ascherio; Peter A LeWitt; Kui Xu; Shirley Eberly; Arthur Watts; Wayne R Matson; Connie Marras; Karl Kieburtz; Alice Rudolph; Mikhail B Bogdanov; Steven R Schwid; Marsha Tennis; Caroline M Tanner; M Flint Beal; Anthony E Lang; David Oakes; Stanley Fahn; Ira Shoulson; Michael A Schwarzschild Journal: Arch Neurol Date: 2009-12