Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
Department of Psychiatry and Psychotherapy, Technische Universität (TU) München, München, Germany.
Alzheimers Res Ther. 2018 Apr 25;10(1):41. doi: 10.1186/s13195-018-0345-3.
With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions.
We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials.
Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures.
Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.
随着针对原发性进行性失语症 (PPA) 患者的治疗干预措施的出现，需要有仪器来随访患者，以描述疾病进展并评估潜在的治疗效果。到目前为止，文献中已经提出了容积脑变化作为临床终点，但仍缺乏认知评分。本研究主要在 1 年内跟踪语言表现方面的疾病进展，并定义了一个可用于治疗干预的 PPA 总分。
我们详细评估了 28 名非流利型 PPA 患者、17 名语义型 PPA 患者、13 名语义流畅型 PPA 患者和 28 名健康对照者，随访时间为 1 年。将最具信息量的神经心理学评估组合成一个总分，并在进行临床试验的样本量计算之前，研究了脑萎缩之间的相关性。
发现 1 年后认知测试的绝对值变化高达 20%。语义和语音流畅性、波士顿命名测试、数字跨度、代币测试、AAT 书面语言和饼干测试被确定为疾病进展的最佳标志物。这些任务为新的 PPA 总分提供了基础。假设治疗效果为认知下降减少 50%，则需要 56 例样本才能发现显著的治疗效果。认知下降与萎缩之间的相关性表明，总分与额部结构（即额上回和额下回）以及左侧皮质下结构之间的相关性高达 r=0.7。
我们的研究结果支持所提出的总分在 PPA 随访中的优异表现，并推荐其作为干预研究中的一种结局测量指标。
