Plasma urate and progression of mild cognitive impairment.
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.


CONCLUSIONS
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.
Irizarry
Michael C
MC
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. michael.c.irizarry@gsk.com
Raman
Rema
R
Schwarzschild
Michael A
MA
Becerra
Lida M
LM
Thomas
Ronald G
RG
Peterson
Ronald C
RC
Ascherio
Alberto
A
Aisen
Paul S
PS
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology; D001900:Boston / Q000453:epidemiology; D003072:Cognition Disorders / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology*; D015986:Confounding Factors, Epidemiologic; D003704:Dementia / Q000453:epidemiology; D018450:Disease Progression; D000077265:Donepezil; D005260:Female; D006801:Humans; D015994:Incidence; D007189:Indans / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D015995:Prevalence; D016019:Survival Analysis; D014527:Uric Acid / Q000097:blood*; D014810:Vitamin E / Q000627:therapeutic use
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D014810:Vitamin E; D014527:Uric Acid; D000077265:Donepezil