帕金森病危险因素 家族史居首

根据一项针对帕金森病(PD)危险因素的最大规模、最全面的系统评价和Meta分析结果，在适合初级保健机构筛查的危险因素中，家庭成员患有PD居于首位(Ann. Neurol. 2012 July 10 [doi: 10.1002/ana.23687])。

伦敦大学学院神经学研究所的Alastair J. Noyce博士及其同事检索了1966~2011年3月间以英文发表的相关文章，将其中的173项研究纳入Meta分析，包括了数十万例患者的队列研究和数万例患者的病例对照研究。

分析结果显示，19种危险因素与PD发病风险变化(提高或降低)存在显著关联，而另外11种因素未见显著相关。对26项病例对照研究资料的Meta分析显示，如果有1名一级亲属患有PD，其自身罹患PD的几率增高3倍；来自19项病例对照研究资料显示，有任何亲属患有PD者的患病几率增加4.5倍。除PD家族史外，其他与发病风险高度相关的因素包括震颤家族史(风险提高2.7倍)、便秘(增高2.3倍)、心境障碍(增高86%)、杀虫剂暴露(增高78%)和头部损伤(增高58%)。作者指出，便秘和心境障碍均被认为是PD的早期症状，可能与PD对脑干的早期影响有关。

该分析还确定了发病几率增加<50%但仍达到统计学意义的4项危险因素：居住在乡村(增高43%)、使用β-受体阻滞剂(增高28%)、从事农场或农业工作(增高26%)以及饮用井水(增高21%)。

其余8项因素与PD发病风险降低呈显著性关联，其中吸烟位居首位。根据26项病例对照研究和7项队列研究资料，与从未吸烟者相比，目前吸烟者PD发病几率下降56%，曾经吸烟者下降36%，过去吸烟者下降22%。其他保护因素包括饮用咖啡(下降33%)、高血压(下降26%)、使用非甾体抗炎药物(下降17%)、使用钙离子通道阻滞剂(下降10%)和饮酒(下降10%)。

作者未发现PD发病几率与口服避孕药、手术绝经、激素替代治疗、阿司匹林、对乙酰氨基酚、他汀类或糖尿病史等其他潜在危险因素或预防药物存在显著关联。

作者报告无相关利益冲突。

爱思唯尔  版权所有

By: MITCHEL L. ZOLER, Internal Medicine News Digital Network

A family member with Parkinson’s disease confers the strongest risk for developing the disease, according to findings from the largest and most comprehensive systematic review and meta-analysis of Parkinson’s disease risk factors suitable for screening in primary care.

People with a first-degree relative with PD had a more than threefold higher odds for developing PD themselves, compared with those without an affected first-degree relative, based on a meta-analysis of data from 26 case-control studies, and people with any relative with PD had a 4.5-fold greater odds, according to data collected in 19 case-control studies, Dr. Alastair J. Noyce and his associates reported (Ann. Neurol. 2012 July 10 [doi: 10.1002/ana.23687]).

Dr. Noyce, a researcher in the Institute of Neurology, University College London, and his colleagues identified 202 English-language articles published during 1966-March 2011, of which 173 made it into the meta-analysis. Included studies involved several hundred thousand patients in cohort studies, and several tens of thousands in case-control studies. The new review and analysis used "an extensive search of observational studies to calculate effect sizes of multiple risk factors for PD," the study authors wrote.

The meta-analysis found 19 risk factors that significantly linked with an altered risk – increased or decreased – for future development of PD, and assessed 11 additional factors that did not show a statistically significant link to PD. Following family history of PD, other strong associations identified in the meta-analysis included:

• Family history of tremor, which boosted the odds for development of PD 2.7-fold, based on results from 10 case-control studies.

• Constipation, considered an early symptom, which was associated with a 2.3-fold greater odds for PD, based on data from one case-control and one cohort study.

• Mood disorder, another early symptom, which was linked to an 86% higher odds of PD, based on data from 11 case-control and 2 cohort studies.

• Pesticide exposure, a risk factor that was linked to a 78% higher odds, according to data from 36 case-control and 2 cohort studies.

• Head injury, a risk factor associated with a 58% greater odds in 19 case-control studies.

Both constipation and mood disorders may correlate with brainstem involvement, an early effect of PD, the authors wrote.

The analysis identified four other risk factors that were linked to an increase in the odds of developing PD of less than 50% but still reached statistical significance: rural residence (43% greater), beta-blocker use (28%), farming or agricultural work (26%), and well water use (21%).

The remaining eight significant risk factors were all associated with reduced odds for PD. Leading this category was smoking. Current smokers had 56% lower odds, compared with never-smokers, based on data from 26 case-control studies and 7 cohort studies. People who had ever smoked had a 36% reduced odds compared with never smokers, and past smokers had a 22% reduced odds. Other protective factors were coffee drinking, linked to a 33% drop in odds; hypertension, linked to a 26% reduction in odds; use of nonsteroidal anti-inflammatory drugs, associated with 17% lower odds; and use of calcium channel blockers and alcohol, each of which was linked to 10% reduced odds.

The analyses failed to find significant links between development of PD and other proposed risk factors or protective agents, including oral contraceptives, surgical menopause, hormone-replacement therapy, aspirin, acetaminophen, statins, or a history of diabetes.

Dr. Noyce and his associates said that they had no disclosures.