Alzheimer's disease (AD) is now conceptualized as a biological entity defined by amyloid and tau deposition and neurodegeneration, with heterogeneous clinical presentations. With the aid of in vivo biomarkers, clinicians are better poised to examine clinical syndromic variability arising from a common pathology. Word retrieval deficits, measured using verbal fluency and confrontation naming tests, are hallmark features of the early clinical stages of the amnestic presentations of AD, specifically in category fluency and naming with relatively spared letter fluency. As yet, there is no consensus regarding performance on these tests in atypical clinical phenotypes of AD, including posterior cortical atrophy (PCA) and logopenic primary progressive aphasia (lvPPA), in individuals who are amyloid-positive (Aβ+) but present with different clinical profiles and patterns of neurodegeneration compared to amnestic AD. The goal of the current study is to determine how Aβ+ individuals across the syndromic spectrum of AD perform on three different word retrieval tasks. A secondary goal is to determine the neuroanatomical substrates underlying word retrieval performance in these Aβ+ individuals. Thirty-two Aβ+ participants with the amnestic presentation, 16 with Aβ+ PCA, 22 with Aβ+ lvPPA, and 99 amyloid-negative (Aβ-) control participants were evaluated with verbal fluency and visual confrontation naming tests as well as high-resolution MRI. The Aβ+ patient groups were rated at very mild or mild levels of severity (CDR 0.5 or 1) and had comparable levels of global cognitive impairment (average MMSE = 23.7 ± 3.9). Behaviorally, we found that the word retrieval profile of PCA patients is comparable to that of amnestic patients, characterized by intact letter fluency but impaired category fluency and visual confrontation naming, while lvPPA patients demonstrated impairment across all tests of word retrieval. Across all AD variants, we observed that letter fluency was associated with cortical thickness in prefrontal, central precuneus, lateral parietal and temporal cortex, while category fluency and naming were associated with cortical thickness in left middle frontal gyrus, posterior middle temporal gyrus, and lateral parietal cortex. Visual confrontation naming was uniquely associated with atrophy in inferior temporal and visual association cortex. We conclude that a better understanding of the word retrieval profiles and underlying neurodegeneration across the AD syndromic spectrum will help improve interpretation of neuropsychological profiles with regard to the localization of neurodegeneration, particularly in the atypical AD variants.

阿尔茨海默氏病（AD）现在被概念化为由淀粉样蛋白和tau沉积以及神经退行性变定义的生物学实体，并具有多种临床表现。借助体内作为生物标志物，临床医生可以更好地检查由常见病理引起的临床症状变异性。使用口语流利度和对抗命名测试测得的单词检索缺陷是AD记忆删除临床早期阶段的标志性特征，特别是类别流利度和相对较闲的字母流利度命名。迄今为止，对于淀粉样蛋白阳性（Aβ+）但表现不同的个体，这些测试在非典型AD临床表型（包括后皮质萎缩（PCA）和徽标性原发性失语（lvPPA））中的表现尚无共识。与遗忘性AD相比，神经变性的临床特征和模式。当前研究的目的是确定AD症状谱中的Aβ+个人如何执行三种不同的单词检索任务。次要目标是确定这些Aβ+个体单词检索性能背后的神经解剖学底物。对32名具有记忆删除功能的Aβ+参与者，16名具有Aβ+ PCA的参与者，22名具有Aβ+ lvPPA的参与者和99名淀粉样蛋白阴性（Aβ-）对照参与者进行了口语流利性和视觉对抗命名测试以及高分辨率的评估核磁共振 Aβ+患者组的严重程度被定为非常轻度或轻度（CDR 0.5或1），并且具有可比较的总体认知障碍水平（平均MMSE = 23.7±3.9）。从行为上，我们发现PCA患者的单词检索模式与记忆删除的患者相当，其特点是完整的字母流利度，但类别流利度和视觉对立命名受损，而lvPPA患者在所有单词检索测试中均表现出障碍。在所有AD变体中，我们观察到字母流畅性与前额叶，中央前突，外侧顶叶和颞皮质的皮层厚度相关，而类别流畅性和命名与左中额回，后颞中回和外侧皮质的厚度相关顶叶皮层 视觉对抗命名与下颞叶和视觉联想皮层的萎缩有独特的关联。