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October 4, 2007 — 尿酸值(UA)中度升高与年长者白质高密度(WMH)的高容量有关，此一发现确定了UA在增加脑血管疾病风险的角色，也可解释老年人UA值升高与轻度知能障碍(MCI)的关系。
约翰霍普金斯大学医学院的研究者发现，UA值高于正常值者的WMH容量是UA值低于平均值者的2.6倍；他们也发现，年纪在60岁以上且UA值高于正常值者的过度缺血性负担风险多出4到5倍。
作者指出，高于正常的UA值显示可以作为年长者轻度知能障碍的标记，目前的结果显示，值得考虑的是，需确认降UA药物是否可以降低尿酸值略高之老年人的缺血性脑疾病或者改善认知功能。
David Schretlen博士所领导的此一研究刊登于10月2日版的神经学(Neurology)期刊。
【强力抗氧化剂】
尿酸过去被视为purine的无活性代谢终产物，作者指出，UA现在被视为强力抗氧化剂，其血中浓度为其他抗氧化剂如维他命C和E的将近10倍。
有些研究者认为UA 可以有神经保护效果，且可以降低神经问题，如阿兹海默氏症的风险；哈佛公共卫生学院最近的研究发现，UA值高与降低巴金森氏症(PD)风险有关，此一发现将对延缓PD病程有所冲击(Weisskopf MG 等人，Am J Epidemiol. 2007;166:561-567)。
另一方面，即使轻微升高的UA值也与高血压、第二型糖尿病、中风、致命的心血管事件、以及轻微认知缺损之风险升高有关。
Schretlen医师和同事最近的研究着眼于65岁以上成人血清UA与认知功能之间的关系，在测量行进速度、语言记忆以及操作记忆时，发现那些UA值高于正常值者，在研究对象中位于最低之四分位的机会高出2.7到5.9倍。
【广泛的公卫冲击】
最近的研究中，研究者意图检视血清UA与WMH之间的关系，进行了社区基础、交叉世代的观察研究，包括 177位年纪在20到92岁之间的男性与女性。
所有的研究对象接受生理与神经检查、精神评估、血液检验、以及生理神经测试，使用T2加权脑部核磁共振(MRI)以及质子浓度扫描测量WMH 容量总数。
女性血清UA浓度范围从1.5到 7.2 mg/dL，男性是 1.6 到 8.2 mg/dL，男性浓度大于 5.75 mg/dL或者女性浓度大于4.8 mg/dL被视为高于正常值；相较于UA值低到中度者， 高于正常值更可能位于WMH容积之最高四分位范围。
这在那些年纪在65岁以上者特别明显，血清 UA 高于正常值更明显与过度的脑缺血疾病有关。
根据Schretlen博士所述，降尿酸剂如allopurinal的临床试验 ，证明长期安全有效，如果进一步的研究确认UA与WMH之间的关联，将可获得授权；作者也指出，因为这些资料系基于有代表性的社区样本，研究发现即使是正常升高的血清UA值也与WMH增加有关，会带来广泛的公卫冲击。
该研究在国家健康研究中心/国家心智健康研究中心、治疗认知神经科学基金会、以及Benjamin & Adith Miller 家族捐赠用于老化、阿兹海默氏症与自闭症之研究等支持下进行。
Increased Ischemic Burden Linked to Elevated Uric Acid Levels
By Caroline Cassels
Medscape Medical News
October 4, 2007 — Mildly elevated levels of uric acid (UA) have been linked to a high volume of white-matter hyperintensities (WMH) in aging adults, a finding that confirms the role of UA in increasing the risk for cerebrovascular disease and that may also explain the link between elevated UA and mild cognitive impairment (MCI) in aging adults.
A study by investigators at Johns Hopkins University School of Medicine, in Baltimore, Maryland, found that individuals with high-normal UA levels had 2.6 times the volume of WMH compared with those with average or low UA.
They also found individuals aged 60 years and older with high-normal UA levels had 4- to 5-fold increased odds of having excessive ischemic burden.
"Given that high-normal serum uric acid appears to be a biomarker of mild cognitive impairment in elderly adults, the current results suggest that determining whether UA-lowering medications can reduce ischemic brain disease or improve cognitive functioning in elderly adults with mildly elevated uric acid merits consideration," the authors write.
Led by David Schretlen, PhD, the study is published in the October 2 issue of Neurology.
Powerful Antioxidant
Once thought to be a metabolically inert end-product of purine, the authors note that UA is now being recognized as a potent antioxidant whose concentration in plasma is nearly 10 times higher than that of other antioxidants, including vitamins C and E.
Some research suggests UA may be neuroprotective and reduce the risk for neurological conditions, including Alzheimer's disease. A recent study by researchers at Harvard School of Public Health found high levels of UA were associated with a decreased risk for Parkinson's disease (PD), a finding that may ultimately have implications for slowing PD progression (Weisskopf MG et al. Am J Epidemiol. 2007;166:561-567).
On the other hand, even mildly elevated UA levels have been linked to an increased risk for hypertension, type 2 diabetes, stroke, and fatal cardiovascular events, as well as mild cognitive impairment.
Recent research by Dr. Schretlen and colleagues looked at the relationship between serum UA and cognitive functioning in adults over the age of 65 years and found those with high-normal UA levels were 2.7 to 5.9 times more likely to score in the lowest quartile of the study sample on measures of processing speed, verbal memory, and working memory.
Broad Public Health Implications
In the current study, investigators sought to examine the relationship between serum UA and WMH volume. The community-based, cross-sectional, observational study included 177 men and women between the ages of 20 and 92 years.
All study subjects underwent a physical and neurologic examination, psychiatric review, laboratory blood studies, and psychoneurological testing. T2- weighted brain magnetic resonance imaging (MRI) and proton density scans were used to measure aggregate WMH volume.
Serum UA concentrations ranged from 1.5 to 7.2 mg/dL for women and 1.6 to 8.2 mg/dL for men. Concentrations of 5.75 mg/dL or greater for men and 4.8 mg/dL or greater for women were classified as high-normal.
Compared with individuals with low to moderate UA levels, participants with high-normal serum UA were more likely to fall in the highest quartile of WMH volume.
This was particularly pronounced in those older than 65 years, where high-normal serum UA was significantly associated with an excessive cerebral ischemic burden.
According to Dr. Schretlen, clinical trials with UA-lowering agents such as allopurinal, which have proven long-term safety and efficacy, may be warranted if further research confirms the link between UA and WMH.
The authors also pointed out that because these data were based on a representative community sample, the study's finding that even normal elevations of serum UA are associated with an increased burden of WMH could have broad public health implications.
The study was supported by the National Institutes of Health/National Institute of Mental Health, the Therapeutic Cognitive Neuroscience Fund, and the Benjamin & Adith Miller Family Endowment on Aging, Alzheimer's, and Autism Research.
Neurology. 2007;69:1418-1423. Abstract