MGH Frontotemporal Dementia Unit, Boston, Massachusetts, USA.
J Neurol Neurosurg Psychiatry. 2011 Jan;82(1):45-51. doi: 10.1136/jnnp.2009.199505. Epub 2010 Jun 20.
To investigate whether some patients with very mild Alzheimer's disease (AD) demonstrate disproportionate executive dysfunction relative to amnesia and how this relates to functional impairment in daily life, future clinical decline, APOE genotype and regional cortical thickness measured from MRI scan data.
The Alzheimer's Disease Neuroimaging Initiative dataset was interrogated for a primary sample of patients with very mild AD dementia (n=100) and a secondary confirmatory sample of patients with mild cognitive impairment (n=396). An executive predominant subgroup was defined as having executive performance ≥2 SDs worse than memory performance and a memory predominant subgroup was defined conversely. A priori regions of interest from a previous study of an AD patient sample were used to obtain cortical thickness measures.
Despite equivalent global measures of impairment (Mini-Mental State Examination, Clinical Dementia Rating (CDR) Sum of Boxes), executive predominant patients (n=88) were more impaired on other executive measures and in the CDR Judgement and Problem Solving box (p<0.005) while memory predominant patients (n=56) were more impaired on other memory measures (p<0.05). The APOE-ε4 allele was much more frequent in the memory predominant subgroup (p<0.0001). Frontoparietal cortical regions were thinner in the executive predominant group than in the memory predominant group (p<0.05).
A dysexecutive clinical phenotype of very mild AD is not rare and is associated with more problem solving difficulties and possibly more rapid progression compared with patients with a predominant amnesic phenotype. Executive predominant AD may reflect an alternative underlying pathophysiology related to genetic status, reflected in more prominent pathological alterations in frontoparietal regions subserving executive function. These findings, which deserve further investigation, may have implications for diagnosis, prognostication, monitoring and related issues involved in clinical research and care.
研究是否有一些非常轻度阿尔茨海默病（AD）患者表现出相对于遗忘症不成比例的执行功能障碍，以及这种障碍与日常生活中的功能障碍、未来的临床衰退、载脂蛋白 E 基因型和从 MRI 扫描数据测量的皮质厚度区域之间的关系。
从阿尔茨海默病神经影像学倡议数据集（Alzheimer's Disease Neuroimaging Initiative dataset）中，对一组有非常轻度 AD 痴呆的患者（n=100）进行了初步分析，并对一组有轻度认知障碍的患者（n=396）进行了二次验证。将执行功能障碍为主的亚组定义为执行功能表现比记忆表现差≥2 个标准差，而将记忆功能障碍为主的亚组定义为相反的情况。以前对 AD 患者样本的研究中使用了预先确定的感兴趣区域（region of interest）来获得皮质厚度测量值。
尽管有相同的全球损害评估（Mini-Mental State Examination，Clinical Dementia Rating （CDR）Sum of Boxes），执行功能障碍为主的患者（n=88）在其他执行功能评估和 CDR 判断和解决问题框中（p<0.005）的受损程度更高，而记忆功能障碍为主的患者（n=56）在其他记忆测试中（p<0.05）的受损程度更高。记忆功能障碍为主的亚组中 APOE-ε4 等位基因更为常见（p<0.0001）。与记忆障碍为主的亚组相比，执行功能障碍为主的亚组的额顶叶皮质区域更薄（p<0.05）。
非常轻度 AD 的执行功能障碍临床表型并不罕见，与以记忆障碍为主的表型相比，它与解决问题的困难更大、可能更快的进展相关。以执行功能障碍为主的 AD 可能反映了与遗传状态有关的另一种潜在病理生理学，表现在执行功能的额顶叶区域有更明显的病理改变。这些发现值得进一步研究，可能对诊断、预后、监测以及临床研究和护理中的相关问题有影响。
