Importance The prevalence of alcohol misuse increased substantially over a decade in adults, particularly in those aged 65 years or older. Ramifications for brain structural integrity are significant, especially in older adults.

Objectives To combine cross-sectional, longitudinal data to test age-alcoholism interactions and examine the association between prevalent comorbidities (drug dependence and hepatitis C virus [HCV] infection) and cortical volume deficits in alcohol dependence.

Design, Setting, and Participants During 14 years, 826 structural magnetic resonance images were acquired in 222 individuals with alcohol dependence and 199 age-matched control participants (aged 25-75 years at initial study), parcellated with a common atlas, and adjusted for brain volume. Longitudinal data were available on 116 participants with alcoholism and 96 control participants. DSM-IV criteria determined alcohol and drug diagnoses; serology testing determined HCV status. The study was conducted at SRI International and Stanford University School of Medicine from April 11, 2003, to March 3, 2017.

Main Outcomes and Measures Magnetic resonance imaging–derived regional cortical volumes corrected for supratentorial volume and sex.

Results Of the 222 participants with alcoholism, 156 (70.3%) were men; mean (SD) age was 48.0 (10.0) years; the mean age for the 199 control participants was 47.6 (14.0) years. Participants with alcohol dependence had volume deficits in frontal (t = −5.732, P < .001), temporal (t = −3.151, P = .002), parietal (t = −5.063, P < .001), cingulate (t = −3.170, P = .002), and insular (t = −4.920, P < .001) cortices; deficits were prominent in frontal subregions and were not sex dependent. Accelerated aging occurred in frontal cortex (t = −3.019, P < .02) and precentral (t = −2.691, P < .05) and superior gyri (t = −2.763, P < .05) and could not be attributed to the amount of alcohol consumed, which was greater in younger-onset than older-onset participants with alcoholism (t = 6.1191, P < .001). Given the high drug-dependence incidence (54.5%) in the alcoholism group, analysis examined drug subgroups (cocaine, cannabis, amphetamines, opiates) compared with drug-dependence–free alcoholism and control groups. Although the alcohol plus cocaine (t = −2.310, P = .04) and alcohol plus opiate (t = −2.424, P = .04) groups had smaller frontal volumes than the drug-dependence–free alcoholism group, deficits in precentral (t = −2.575, P = .01), supplementary motor (t = −2.532, P = .01), and medial (t = −2.800, P = .01) volumes endured in drug-dependence–free participants with alcoholism compared with control participants. Those with HCV infection had greater deficits than those without HCV infection in frontal (t = 3.468, P = .01), precentral (t = 2.513, P = .03), superior (t = 2.533, P = .03), and orbital (t = 2.506, P = .03) volumes, yet total frontal (t = 2.660, P = .02), insular (t = 3.526, P = .003), parietal (t = 2.414, P = .03), temporal (t = 3.221, P = .005), and precentral (t = 3.180, P = .01) volume deficits persisted in the uninfected participants with alcoholism compared with control participants with known HCV status.

Conclusions and Relevance Drug dependence and HCV infection compounded deleterious effects of alcohol dependence on frontal cortical volumes but could not account for the frontally distributed volume deficits in the drug-free participants with alcoholism. We speculate that age-alcohol interactions notable in frontal cortex put older adults at heightened risk for age-associated neurocompromise even if alcohol misuse is initiated later in life.

重要性十年来，成年人，尤其是 65 岁或以上的成年人，酗酒的发生率大幅上升。对大脑结构完整性的影响是显着的，尤其是对于老年人。

目的结合横断面、纵向数据来测试年龄与酗酒之间的相互作用，并检查流行的合并症（药物依赖和丙型肝炎病毒 [HCV] 感染）与酒精依赖中皮质体积缺陷之间的关联。

设计、设置和参与者在 14 年期间，从 222 名酒精依赖者和 199 名年龄匹配的对照参与者（初始研究时年龄为 25-75 岁）采集了 826 张结构磁共振图像，用通用图谱进行分割，并根据脑容量。可获得 116 名酗酒参与者和 96 名对照参与者的纵向数据。 DSM-IV 标准确定酒精和药物诊断；血清学检测可确定 HCV 状态。该研究于2003年4月11日至2017年3月3日在SRI国际和斯坦福大学医学院进行。

主要结果和措施磁共振成像衍生的区域皮质体积根据幕上体积和性别进行校正。

结果222 名酗酒者中，男性 156 名（70.3%）；平均 (SD) 年龄为 48.0 (10.0) 岁； 199 名对照参与者的平均年龄为 47.6 (14.0) 岁。酒精依赖的参与者的额叶（t = -5.732，P < .001）、颞叶（t = -3.151，P = .002）、顶叶（t = -5.063，P < .001）、扣带回（t = −3.170，P = .002) 和岛叶 (t = −4.920，P < .001) 皮质；额叶次区域的缺陷很明显，并且与性别无关。加速衰老发生在额叶皮层（t = -3.019，P < .02）和中央前回（t = -2.691，P < .05）和上回（t = -2.763，P < .05），并且不能归因于饮酒量，较年轻发病的酒精中毒参与者多于较年长发病的酒精中毒参与者 (t = 6.1191，P < .001)。鉴于酒精中毒组药物依赖发生率较高（54.5%），分析检查了药物亚组（可卡因、大麻、安非他明、阿片类药物）与无药物依赖酒精中毒组和对照组的比较。尽管酒精加可卡因（t = -2.310，P = .04）和酒精加阿片类药物（t = -2.424，P = .04）组的额叶体积比无药物依赖酒精中毒组小，但中央前区（与酒精中毒的无药物依赖参与者相比，t = -2.575，P = .01）、补充运动（t = -2.532，P = .01）和内侧（t = -2.800，P = .01）容量与控制参与者。与未感染 HCV 的患者相比，感染 HCV 的患者在额叶 (t = 3.468，P = .01)、中央前 (t = 2.513，P = .03)、上侧 (t = 2.533，P = .03) 和上侧的缺陷更大。眼眶（t = 2.506，P = .03）体积，但总额叶（t = 2.660，P = .02），岛叶（t = 3.526，P = .003），顶叶（t = 2.414，P = .03） ，时间（t = 3.221，P = .005) 和中央前 (t = 3.180, P = .01) 容量不足在未感染的酗酒参与者中与已知 HCV 状态的对照参与者相比持续存在。

结论和相关性药物依赖和 HCV 感染加剧了酒精依赖对额叶皮层体积的有害影响，但不能解释酒精中毒的无毒品参与者的额叶分布体积缺陷。我们推测，即使在晚年开始滥用酒精，额叶皮层中显着的年龄-酒精相互作用也会使老年人面临与年龄相关的神经损害的更高风险。