Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Lancet Neurol. 2021 Mar;20(3):222-234. doi: 10.1016/S1474-4422(20)30440-3.
Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease.
大多数阿尔茨海默病患者表现出健忘问题；然而，相当一部分患者（在早发性病例中更为突出）具有非典型表型，包括主要的视觉、语言、执行、行为或运动功能障碍。过去，这些患者通常得到较晚的诊断；然而，由于阿尔茨海默病病理的 CSF 和 PET 生物标志物的可用性，以及将非典型形式的阿尔茨海默病纳入新的诊断标准，越来越多的患者能够在疾病早期得到更有信心的诊断。这种早期诊断反过来又使患者能够获得量身定制的信息、适当的护理和支持，以及个性化的治疗计划。这些进展将为临床试验提供更好的机会，因为临床试验通常排除非典型表型。对非典型阿尔茨海默病的研究揭示了阿尔茨海默病谱中以前未被识别的神经病理学异质性。神经影像学、遗传学、生物标志物和基础科学研究为可能导致不同大脑网络选择性脆弱性的因素提供了关键见解，这对理解典型的晚发性阿尔茨海默病具有潜在的机制意义。
