From the Departments of Psychiatry (J.L.S., P.C.N.) and Neurology (J.L.S., P.C.N.), Carver College of Medicine at the University of Iowa; Division of Pharmacy Practice and Sciences (J.L.S.), University of Iowa College of Pharmacy, Iowa City; Department of Neurology (C.S.), Huntington Center NRW, Ruhr-University Bochum, St Josef-Hospital, Bochum, Germany; and Stead Family Children's Hospital at the University of Iowa (P.C.N.), Iowa City.
Neurology. 2021 May 11;96(19):e2407-e2413. doi: 10.1212/WNL.0000000000011823. Epub 2021 Mar 10.
To investigate the relationships between CAG repeat length in the huntingtin gene and cognitive performance in participants above and below the disease threshold for Huntington disease (HD), we performed a cross-sectional analysis of the Enroll-HD database.
We analyzed data from young, developing adults (≤30 years of age) without a history of depression, apathy, or cognitive deficits. We included participants with and without the gene expansion (CAG ≥36) for HD. All participants had to have a Total Functional Capacity Score of 13, a diagnostic confidence level of zero, and a total motor score of <10 and had to be >28.6 years from their predicted motor onset. We performed regression analyses to investigate the nonlinear relationship between CAG repeat length and various cognitive measures controlling for age, sex, and education level.
There were significant positive relationships between CAG repeat length and the Symbol Digit Modalities, Stroop Color Naming, and Stroop Interference test scores. There were significant negative relationships between CAG repeat length and scores on Parts A and B of the Trails Making Test ( < 0.05), indicating that longer CAG repeat lengths were associated with better performance.
An increasing number of CAG repeats in the huntingtin gene below disease threshold and low pathologic CAG ranges were associated with some improvements in cognitive performance. These findings outline the relationship between CAG repeats within the huntingtin gene and cognitive development.
This study provides Class IV evidence that CAG repeat length is positively associated with cognitive function across a spectrum of CAG repeat lengths.
为了探究亨廷顿病（HD）疾病阈值以上和以下的参与者的亨廷顿基因 CAG 重复长度与认知表现之间的关系，我们对 Enroll-HD 数据库进行了横断面分析。
我们分析了没有抑郁、冷漠或认知缺陷病史的年轻发育中的成年人（≤30 岁）的数据。我们纳入了具有和不具有 HD 基因扩展（CAG≥36）的参与者。所有参与者的总功能能力评分必须为 13，诊断置信度水平为零，总运动评分<10，并且必须距离其预测的运动发作时间>28.6 年。我们进行回归分析，以在控制年龄、性别和教育水平的情况下，调查 CAG 重复长度与各种认知测量之间的非线性关系。
CAG 重复长度与符号数字模态、Stroop 颜色命名和 Stroop 干扰测试分数之间存在显著的正相关关系。CAG 重复长度与 Trails 制作测试的 A 部分和 B 部分的分数之间存在显著的负相关关系（<0.05），这表明 CAG 重复长度越长，表现越好。
在疾病阈值以下和较低的病理 CAG 范围内，亨廷顿基因中的 CAG 重复增加与一些认知表现的提高有关。这些发现概述了亨廷顿基因内 CAG 重复与认知发展之间的关系。
这项研究提供了 IV 级证据，表明 CAG 重复长度与认知功能呈正相关，跨越了一系列 CAG 重复长度。
