Vascular and dopaminergic contributors to mild parkinsonian signs in older adults
Vascular and dopaminergic contributors to mild parkinsonian signs in older adults
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DOI：
10.1212/wnl.0000000000004842
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发表时间：
2018-01-16
期刊：
影响因子：
9.9
通讯作者：
Rosano, Caterina
中科院分区：
文献类型：
--
作者：
Rosso, Andrea L.;Bohnen, Nicolaas I.;Rosano, Caterina
目的
轻度帕金森体征（MPS）是老年人中一种未得到充分重视的神经系统疾病；我们评估了MPS与多巴胺能（儿茶酚 - O - 甲基转移酶[COMT]基因型，突触多巴胺水平的一个指标）和血管（白质高信号[WMH]，脑小血管疾病的一个指标）因素的相关性。
方法
在一组老年人（平均年龄82.6岁[标准差2.6]；58.0%为女性；38.8%为黑人）中，我们通过针对人口统计学和健康特征进行调整的回归模型，评估了WMH体积和COMT Val158Met（rs4680）基因型（n = 35 Met/Met，n = 180 Val携带者）与MPS的横断面相关性。评估了WMH和COMT之间的相互作用，并按COMT基因型进行分层重复分析（Met/Met与较高的突触多巴胺相关，而Val携带者与较低的突触多巴胺相关）。
结果
我们的样本中有42.3%存在MPS。WMH（比值比[OR] 1.16，置信区间[CI] 1.05 - 1.27）与MPS相关，而COMT（Met/Met与Val携带者相比：OR 0.62，CI 0.27 - 1.42）则无关。WMH和COMT之间存在显著的相互作用（p = 0.03）。分层分析显示，在COMT Val携带者中WMH与MPS之间有很强的相关性（OR 1.23，CI 1.09 - 1.38），但在Met/Met中则无（OR 0.68，CI 0.45 - 1.02），且与协变量无关。
结论
WMH与MPS有直接关系。相比之下，COMT与MPS无关，但它确实改变了WMH对MPS的影响。多巴胺能系统可能对WMH对MPS的影响起到补偿作用。这些发现表明，在老年人中MPS源于血管因素而非多巴胺能因素，但这两个因素在MPS的表现中都很重要。
ObjectiveMild parkinsonian signs (MPS) are an underappreciated neurologic condition in older adults; we assessed associations of MPS with measures of dopaminergic (catechol-O-methyltransferase [COMT] genotype, an indicator of synaptic dopamine levels) and vascular (white matter hyperintensities [WMH], an indicator of cerebral small vessel disease) factors.MethodsIn a cohort of older adults (mean age 82.6 years [SD 2.6]; 58.0% female; 38.8% black), we assessed cross-sectional associations of WMH volume and COMT Val158Met (rs4680) genotype (n = 35 Met/Met, n = 180 Val carriers) with MPS by regression models adjusted for demographic and health characteristics. Interactions between WMH and COMT were assessed and analyses were repeated stratified by COMT genotype (Met/Met related to higher synaptic dopamine vs Val carriers related to lower synaptic dopamine).ResultsMPS was present in 42.3% of our sample. WMH (odds ratio [OR] 1.16, confidence interval [CI] 1.05-1.27) but not COMT (Met/Met compared to Val carrier: OR 0.62, CI 0.27-1.42) was related to MPS. There was a significant interaction between WMH and COMT (p = 0.03). Stratified analyses reveled a strong association between WMH and MPS among COMT Val carriers (OR 1.23, CI 1.09-1.38), but not for Met/Met (OR 0.68, CI 0.45-1.02), independent of covariates.ConclusionsWMH had a direct relation with MPS. In contrast, COMT was not associated with MPS, but it did modify the effect of WMH on MPS. The dopaminergic system may provide compensation for the effects of WMH on MPS. These findings suggest that MPS has a vascular rather than dopaminergic origin in older adults, but both factors are important in MPS manifestation.