Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Neuroscience Program, SRI International, Menlo Park, CA, USA.
Addict Biol. 2019 Mar;24(2):290-302. doi: 10.1111/adb.12584. Epub 2017 Dec 15.
Variations in pattern and extent of cognitive and motor impairment occur in alcoholism (ALC). Causes of such heterogeneity are elusive and inconsistently accounted for by demographic or alcohol consumption differences. We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment. Participants with ALC (n = 96) and a normal comparison group (n = 41) were examined on six cognitive and motor domains. Signs of historically determined subclinical Wernicke's encephalopathy were detected using the Caine et al. criteria, which were based on postmortem examination and chart review of antemortem data of alcoholic cases with postmortem evidence for Wernicke's encephalopathy. Herein, four Caine criteria provided quantification of dietary deficiency, cerebellar dysfunction, low general cognitive functioning and oculomotor abnormalities in 86 of the 96 ALC participants. Subgroups based on Caine criteria yielded a graded effect, where those meeting more criteria exhibited greater impairment than those meeting no to fewer criteria. These results could not be accounted for by history of drug dependence. Multiple regression indicated that compromised performance on ataxia, indicative of cerebellar dysfunction, predicted non-mnemonic and upper motor deficits, whereas low whole blood thiamine level, consistent with limbic circuit dysfunction, predicted mnemonic deficits. This double dissociation indicates biological markers that contribute to heterogeneity in expression of functional impairment in ALC. That non-mnemonic and mnemonic deficits are subserved by the dissociable neural systems of frontocerebellar and limbic circuitry, both commonly disrupted in ALC, suggests neural mechanisms that can differentially affect selective functions, thereby contributing to heterogeneity in pattern and extent of dysfunction in ALC.
酒精中毒(ALC)患者的认知和运动损伤模式和程度存在差异。造成这种异质性的原因难以捉摸,且无法用人口统计学或饮酒差异来解释。我们研究了神经和营养因素,以探究其是否可能是导致损伤异质性的原因。我们对 96 名 ALC 患者和 41 名正常对照组进行了六项认知和运动领域的检查。使用 Caine 等人的标准检测到历史上确定的亚临床威尼克脑病的迹象,该标准基于酒精性病例的尸检和生前数据图表审查,这些病例有威尼克脑病的尸检证据。在此,四项 Caine 标准对 96 名 ALC 患者中的 86 名进行了量化评估,这些标准评估了饮食缺乏、小脑功能障碍、一般认知功能低下和眼球运动异常。基于 Caine 标准的亚组产生了分级效应,符合更多标准的患者比符合较少标准的患者损伤更严重。这些结果不能用药物依赖史来解释。多元回归表明,代表小脑功能障碍的共济失调表现受损,预测了非记忆和上运动缺陷,而全血硫胺素水平降低,提示边缘回路功能障碍,预测了记忆缺陷。这种双重分离表明,生物标志物导致了 ALC 中功能损伤表达的异质性。非记忆和记忆缺陷由额-小脑和边缘回路的分离神经网络提供支持,而这两个神经网络在 ALC 中都经常受到干扰,这表明神经机制可以以不同的方式影响选择性功能,从而导致 ALC 中功能障碍模式和程度的异质性。