Northwestern University, Cognitive Neurology and Alzheimer's Disease Center (CNADC), 320 E Superior Street, Searle Building 11th Floor, Chicago, IL 60611, USA.
Neurology. 2011 May 24;76(21):1804-10. doi: 10.1212/WNL.0b013e31821ccd3c.
To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials.
Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S).
There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere.
The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects.
在 2 年的时间内观察原发性进行性失语症（PPA）的纵向病程，并提供可用于指导治疗干预试验设计和评估的预期变化的定量范围。
在符合语言流畅性降低、语法缺失和语义 PPA 亚型研究标准的 13 名严格特征患者中，评估基线和 2 年后皮质厚度和全脑皮质体积损失的区域变化以及神经心理学语言表现。
在 2 年内，临床缺陷和皮质萎缩有了实质性的进展。神经心理学语言表现模式失去了区分一种 PPA 变体与另一种变体的明显区别。尽管如此，词理解与语法处理的亚型特异性差异损害在很大程度上得以维持。最大萎缩部位超出了每个 3 个亚型特征的初始独特位置，并显示出更趋同的分布，涵盖了语言网络的所有 3 个主要组成部分：下额叶、颞顶交界处和外侧颞叶皮层。尽管存在进展，但总体最大萎缩仍偏向左侧半球。
结果表明，在早期到中期明显区分 PPA 变体的独特特征，随着变性变得更加严重，可能会失去其独特性。鉴于 2 年内大量的萎缩，PPA 临床试验可能需要比阿尔茨海默病试验更少的患者和更短的研究时间，才能检测到显著的治疗效果。
