Urate as a predictor of the rate of clinical decline in Parkinson disease.
Urate as a predictor of the rate of clinical decline in Parkinson disease.
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DOI：
10.1001/archneurol.2009.247
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发表时间：
2009-12
影响因子：
--
通讯作者：
Schwarzschild, Michael A.
中科院分区：
文献类型：
--
作者：
Ascherio, Alberto;LeWitt, Peter A.;Xu, Kui;Eberly, Shirley;Watts, Arthur;Matson, Wayne R.;Marras, Connie;Kieburtz, Karl;Rudolph, Alice;Bogdanov, Mikhail B.;Schwid, Steven R.;Tennis, Marsha;Tanner, Caroline M.;Beal, M. Flint;Lang, Anthony E.;Oakes, David;Fahn, Stanley;Shoulson, Ira;Schwarzschild, Michael A.
帕金森病(PD)的风险及其进展速度可能会随着主要抗氧化剂血尿酸盐的增加而下降。目的：确定血清和脑脊液中尿酸盐浓度是否可以预测帕金森病患者的临床进展。800名早期帕金森病患者参加了DATATOP试验。774名受试者测定治疗前血清尿酸，713名受试者测定脑脊液尿酸。需要左旋多巴治疗的临床残疾的治疗、年龄和性别调整的风险比(HRs)，这是预先指定的主要终点。进展到终点的心率随着血尿酸的升高而降低(1个标准差的心率增加=0.82；95%CI=0.73~0.93)。在按α-生育酚治疗(2,000IU/天)分层的分析中，仅在未接受α-生育酚治疗的受试者中，主要终点的心率下降(HR=0.75；95%CI=0.62至0.89，而接受治疗的HR=0.9；95%CI=0.75至1.08)。联合帕金森病评定量表(UPDRS)的变化率结果类似。脑脊液尿酸还与主要终点(最高与最低五分位数的HR=0.65；95%CI：0.54至0.96)和UPDRS的变化率呈负相关。与血清尿酸一样，这些关联仅存在于未接受α-生育酚治疗的受试者中。基线时较高的血清和脑脊液尿酸与较慢的临床下降率相关。这些发现加强了尿酸和帕金森病之间的联系，以及考虑将中枢神经系统尿酸盐升高作为减缓帕金森病进展的潜在策略的理由。
The risk of Parkinson disease (PD) and its rate of progression may decline with increasing blood urate, a major antioxidant. To determine whether serum and cerebrospinal fluid (CSF) concentrations of urate predict clinical progression in patients with PD. 800 subjects with early PD enrolled in the DATATOP trial. Pre-treatment urate was measured in serum for 774 subjects and in CSF for 713. Treatment-, age- and sex-adjusted hazard ratios (HRs) for clinical disability requiring levodopa therapy, the pre-specified primary endpoint. The HR of progressing to endpoint decreased with increasing serum urate (HR for 1 standard deviation increase = 0.82; 95% CI = 0.73 to 0.93). In analyses stratified by α-tocopherol treatment (2,000 IU/day), a decrease in the HR for the primary endpoint was seen only among subjects not treated with α-tocopherol (HR = 0.75; 95% CI = 0.62 to 0.89, versus those treated HR = 0.90; 95% CI = 0.75 to 1.08). Results were similar for the rate of change in the United Parkinson Disease Rating Scale (UPDRS). CSF urate was also inversely related to both the primary endpoint (HR for highest versus lowest quintile = 0.65; 95% CI: 0.54 to 0.96) and to the rate of change in UPDRS. As with serum urate, these associations were present only among subjects not treated with α-tocopherol. Higher serum and CSF urate at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate and PD and the rationale for considering CNS urate elevation as a potential strategy to slow PD progression.
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DOI：
10.1159/000170883
发表时间：
2009
期刊：
Neuro-degenerative diseases
影响因子：
--
作者：
Irizarry MC;Raman R;Schwarzschild MA;Becerra LM;Thomas RG;Peterson RC;Ascherio A;Aisen PS
通讯作者：
Aisen PS
影响因子：
10.6
作者：
DEGRELL, I;NAGY, E
通讯作者：
NAGY, E
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
8.3
作者：
Bos, Michiel J.;Koudstaal, Peter J.;Breteler, Monique M. B.
通讯作者：
Breteler, Monique M. B.
影响因子：
3.5
作者：
Haberman, Frank;Tang, Sung-Chun;Mattson, Mark P.
通讯作者：
Mattson, Mark P.