Does serum uric acid act as a modulator of cerebrospinal fluid Alzheimer's disease biomarker related cognitive decline?

B. S. Ye; W. W. Lee; J. H. Ham; J. J. Lee; P. H. Lee; Y. H. Sohn

doi:10.1111/ene.12969

Does serum uric acid act as a modulator of cerebrospinal fluid Alzheimer's disease biomarker related cognitive decline?

B. S. Ye, W. W. Lee, J. H. Ham, J. J. Lee, P. H. Lee, Y. H. Sohn

Department of Neurology

Research output: Contribution to journal › Article › peer-review

34 Citations (Scopus)

Abstract

Background and purpose: The association of serum uric acid, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and longitudinal cognitive decline was evaluated using the AD Neuroimaging Initiative database. Methods: In 271 healthy subjects, 596 mild cognitive impairment patients and 197 AD patients, serum uric acid and CSF AD biomarkers were measured at baseline, and Mini-Mental State Examination and AD Assessment Scale - Cognitive Subscale (ADAS-cog) were assessed serially (mean duration, 2.9 years). The effect of uric acid on longitudinal cognitive decline was evaluated using linear mixed effect models for Mini-Mental State Examination and ADAS-cog scores in female and male subjects separately, with possible confounders controlled (model 1). To determine the effects of uric acid independent of CSF biomarker (Aβ_1-42 or tau) and to test whether the detrimental effects of CSF biomarker differ according to uric acid, CSF biomarker and its interaction with uric acid were further included in model 1 (model 2). Results: Higher levels of uric acid were associated with slower cognitive decline, particularly in the mild cognitive impairment and dementia subgroups, and more prominently in female subjects. Model 2 with CSF Aβ_1-42 showed that higher levels of uric acid were associated with a slower cognitive decline and alleviated the detrimental effect of Aβ_1-42 on cognitive decline. Model 2 with CSF tau showed that higher levels of uric acid alleviated the detrimental effect of tau on cognitive decline in female subjects but not in male subjects. Conclusion: Higher levels of uric acid had protective effects on longitudinal cognitive decline independent of and interactively with CSF AD biomarkers.

Original language	English
Pages (from-to)	948-957
Number of pages	10
Journal	European Journal of Neurology
Volume	23
Issue number	5
DOIs	https://doi.org/10.1111/ene.12969
Publication status	Published - 2016 May 1

Bibliographical note

Funding Information:
Data used in the preparation of this paper were obtained from the ADNI database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and /or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.lo ni.usc.edu/wp-content/uploads/how_to_apply/ADNI_ Acknowledgement_List.pdf. Funded by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech Inc.; Fujirebio; GE Healthcare;; IXICO Ltd; Janssen Alzheimer Immunotherapy Research and Development LLC; Johnson & Johnson Pharmaceutical Research and Development LLC; Medpace Inc.; Merck and Co. Inc.; Meso Scale Diagnostics LLC; NeuroRx Research ; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

Publisher Copyright:
© 2016 European Academy of Neurology.

All Science Journal Classification (ASJC) codes

Neurology
Clinical Neurology

Access to Document

10.1111/ene.12969

Cite this

@article{a709e5d3a0b9494bb32d02a922e22f37,

title = "Does serum uric acid act as a modulator of cerebrospinal fluid Alzheimer's disease biomarker related cognitive decline?",

abstract = "Background and purpose: The association of serum uric acid, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and longitudinal cognitive decline was evaluated using the AD Neuroimaging Initiative database. Methods: In 271 healthy subjects, 596 mild cognitive impairment patients and 197 AD patients, serum uric acid and CSF AD biomarkers were measured at baseline, and Mini-Mental State Examination and AD Assessment Scale - Cognitive Subscale (ADAS-cog) were assessed serially (mean duration, 2.9 years). The effect of uric acid on longitudinal cognitive decline was evaluated using linear mixed effect models for Mini-Mental State Examination and ADAS-cog scores in female and male subjects separately, with possible confounders controlled (model 1). To determine the effects of uric acid independent of CSF biomarker (Aβ1-42 or tau) and to test whether the detrimental effects of CSF biomarker differ according to uric acid, CSF biomarker and its interaction with uric acid were further included in model 1 (model 2). Results: Higher levels of uric acid were associated with slower cognitive decline, particularly in the mild cognitive impairment and dementia subgroups, and more prominently in female subjects. Model 2 with CSF Aβ1-42 showed that higher levels of uric acid were associated with a slower cognitive decline and alleviated the detrimental effect of Aβ1-42 on cognitive decline. Model 2 with CSF tau showed that higher levels of uric acid alleviated the detrimental effect of tau on cognitive decline in female subjects but not in male subjects. Conclusion: Higher levels of uric acid had protective effects on longitudinal cognitive decline independent of and interactively with CSF AD biomarkers.",

author = "Ye, {B. S.} and Lee, {W. W.} and Ham, {J. H.} and Lee, {J. J.} and Lee, {P. H.} and Sohn, {Y. H.}",

note = "Funding Information: Data used in the preparation of this paper were obtained from the ADNI database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and /or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.lo ni.usc.edu/wp-content/uploads/how_to_apply/ADNI_ Acknowledgement_List.pdf. Funded by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer{\textquoteright}s Association; Alzheimer{\textquoteright}s Drug Discovery Foundation; Araclon Biotech; BioClinica Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech Inc.; Fujirebio; GE Healthcare;; IXICO Ltd; Janssen Alzheimer Immunotherapy Research and Development LLC; Johnson & Johnson Pharmaceutical Research and Development LLC; Medpace Inc.; Merck and Co. Inc.; Meso Scale Diagnostics LLC; NeuroRx Research ; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer{\textquoteright}s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2016 European Academy of Neurology.",

year = "2016",

month = may,

day = "1",

doi = "10.1111/ene.12969",

language = "English",

volume = "23",

pages = "948--957",

journal = "European Journal of Neurology",

issn = "1351-5101",