Jones David, Pelak Victoria, Rogalski Emily
Continuum (Minneap Minn). 2024 Dec 1;30(6):1614-1641. doi: 10.1212/CON.0000000000001504.
This article provides a comprehensive review of the distinct features of four atypical Alzheimer disease (AD) variants: dysexecutive AD, behavioral variant AD, posterior cortical atrophy, and the logopenic variant of primary progressive aphasia. It also elucidates their clinical presentations, underlying pathophysiologic pathways, diagnostic indicators, and management requirements.
Recent research has revealed that these atypical AD forms vary not only in clinical manifestations but in their functional neuroanatomy spanning a common pathophysiologic spectrum. Imaging techniques, such as MRI, fludeoxyglucose positron emission tomography (FDG-PET), and tau PET, have identified distinct abnormalities in specific brain regions associated with each variant. This same variability is less tightly coupled to amyloid imaging. Emerging diagnostic and therapeutic strategies should be tailored to each variant's unique features.
Atypical forms of AD often present with symptoms that are predominantly nonmemory related, distinguishing them from the more common memory-centric presentation of the disease. Two distinct clinical and pathologic entities, dysexecutive AD and behavioral variant AD, have replaced the outdated term frontal AD. Posterior cortical atrophy is another variant that mainly affects higher-order visual functions, which can lead to misdiagnoses because of its atypical symptom profile. Logopenic primary progressive aphasia is marked by difficulties in word retrieval, a challenge that may not be readily apparent if the person compensates by using circumlocution. Modern diagnostic techniques, such as MRI, PET, and biomarker analysis, have proven crucial for the accurate diagnosis and differentiation of these atypical AD variants. In treating these forms, it is critical to use tailored therapeutic interventions that combine pharmacotherapy with nonpharmacologic strategies to effectively manage the disease.
本文全面综述了四种非典型阿尔茨海默病（AD）变体的独特特征：执行功能障碍型AD、行为变异型AD、后皮质萎缩以及原发性进行性失语的语义性变异型。本文还阐明了它们的临床表现、潜在的病理生理途径、诊断指标及管理要求。
最近的研究表明，这些非典型AD形式不仅在临床表现上有所不同，而且在跨越共同病理生理谱的功能性神经解剖学上也存在差异。成像技术，如MRI、氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）和tau PET，已在与每种变体相关的特定脑区发现了明显异常。这种相同的变异性与淀粉样蛋白成像的关联较弱。新兴的诊断和治疗策略应根据每种变体的独特特征进行调整。
AD的非典型形式通常表现出主要与记忆无关的症状，这使其有别于该疾病更常见的以记忆为中心的表现形式。两种不同的临床和病理实体，即执行功能障碍型AD和行为变异型AD，已取代了过时的术语额叶型AD。后皮质萎缩是另一种主要影响高级视觉功能的变体，由于其非典型的症状特征，可能导致误诊。语义性原发性进行性失语的特点是单词检索困难，如果患者通过迂回表达进行代偿，这一挑战可能并不明显。现代诊断技术，如MRI、PET和生物标志物分析，已被证明对准确诊断和区分这些非典型AD变体至关重要。在治疗这些形式的AD时，至关重要的是使用量身定制的治疗干预措施，将药物治疗与非药物策略相结合，以有效管理该疾病。
