Wellcome Centre for Mitochondrial Research Institute of Neuroscience Newcastle University Newcastle upon Tyne NE2 4HH United Kingdom.
Institute of Health & Society Newcastle University 3rd Floor, Sir James Spence Institute Royal Victoria Infirmary Queen Victoria Road Newcastle upon Tyne NE1 4LP United Kingdom.
Ann Clin Transl Neurol. 2019 Mar 27;6(5):826-836. doi: 10.1002/acn3.736. eCollection 2019 May.
To determine the cognitive profile of adult patients with mitochondrial disease, and the effect of disease severity on cognition.
Using a prospective case-control design, we compared cognition of patients to normative data and to matched controls, assessed three times over 18 months. Forty-nine patients with m.3243A>G ( = 36) and m.8344A>G ( = 13) mtDNA mutations and 32 controls, matched by age (±5 years) and premorbid cognition (±10 WTAR FSIQ points), participated. Participants completed neuropsychological assessments of general cognition (WAIS-IV), executive function (D-KEFS), and memory (WMS-IV). Potential predictors of cognition were explored.
Patients show mild-to-moderate premorbid cognitive impairment, but substantial impairment in current general cognition and distinct domains, including verbal comprehension, perceptual reasoning, working memory, processing speed, and memory retrieval. Executive dysfunction may be caused by slower decision-making. Patients performed worse than controls, except on memory tasks, indicating intact memory, when premorbid cognition is controlled for. Premorbid cognition and disease severity were consistent predictors of cognition in patients; however, cognitive decline appears slow and is unlikely in the short-term, when other disease-specific factors remain stable.
Patients should be monitored to facilitate early identification of a complex profile of cognitive deficits and individuals with higher disease burden should be followed up more closely. On development of cognitive difficulties, appropriate compensatory strategies should be determined through in-depth assessment. Using strategies such as slower presentation of information, multiple modes of presentation, active discussion to aid understanding and decision-making, and use of memory aids, may ameliorate difficulties.
确定成年线粒体病患者的认知特征，以及疾病严重程度对认知的影响。
采用前瞻性病例对照设计，我们比较了患者与正常数据和匹配对照的认知，在 18 个月内进行了三次评估。49 名患有 m.3243A>G（=36）和 m.8344A>G（=13）mtDNA 突变的患者和 32 名匹配的对照者参与了研究，这些对照者按年龄（±5 岁）和发病前认知（±10 WTAR FSIQ 点）进行匹配。参与者完成了一般认知（WAIS-IV）、执行功能（D-KEFS）和记忆（WMS-IV）的神经心理学评估。探讨了认知的潜在预测因素。
患者表现出轻度至中度发病前认知障碍，但在当前一般认知和特定领域，包括言语理解、知觉推理、工作记忆、加工速度和记忆检索方面存在明显障碍。执行功能障碍可能是由于决策速度较慢所致。患者的表现不如对照组，除了记忆任务，这表明记忆完整，当控制发病前认知时。发病前认知和疾病严重程度是患者认知的一致预测因素；然而，在其他疾病特异性因素保持稳定的情况下，认知衰退似乎缓慢且在短期内不太可能发生。
应监测患者，以促进对认知缺陷复杂特征的早期识别，并应更密切地随访疾病负担较高的个体。一旦出现认知困难，应通过深入评估确定适当的补偿策略。使用信息呈现速度较慢、多种呈现方式、主动讨论以帮助理解和决策、以及使用记忆辅助工具等策略，可能会改善困难。
