Background: There is an increased effort to better understand neuropsychiatric symptoms of Alzheimer’s Disease (AD) as an important feature of symptomatic burden as well as potential modifiable factors of the disease process. Anxiety is one of the most common neuropsychiatric symptoms in Alzheimer’s Disease (AD). A growing body of work has emerged that addresses the epidemiology and biological correlations of anxiety in AD.

Methods: Here, we review human studies in research and clinical cohorts that examined anxiety in AD. We focused on work related to prevalence across AD stages, correlation with established biomarkers, relationship with AD neuropathology and genetic risk factors, and impact on progression.

Results: Anxiety is prominent in the early stages and increases across the spectrum of functional stages. Biomarker relationships are strongest at the level of FDG-PET and amyloid measured via PET or cerebrospinal fluid analysis. Neuropathologically, anxiety emerges with early Braak stage tau pathology. The presence of the apolipoprotein E e4 allele is associated with increased anxiety at all stages, most notably at mild cognitive impairment. Anxiety portended a faster progression at all predementia stages.

Conclusion: This body of work suggests a close biological relationship between anxiety and AD that begins in early stages and influences functional decline. As such, we discuss future work that would improve our understanding of this relationship and test the validity of anxiolytic treatment as disease modifying therapy for AD.

背景：人们越来越努力地更好地了解阿尔茨海默病（AD）的神经精神症状，将其作为症状负担的重要特征以及疾病过程的潜在可改变因素。焦虑是阿尔茨海默病（AD）最常见的神经精神症状之一。越来越多的研究工作致力于解决 AD 焦虑的流行病学和生物学相关性。

方法：在这里，我们回顾了研究和临床队列中检查 AD 焦虑的人类研究。我们重点关注与 AD 各个阶段的患病率、与已建立的生物标志物的相关性、与 AD 神经病理学和遗传风险因素的关系以及对进展的影响相关的工作。

结果：焦虑在早期阶段很突出，并在整个功能阶段中增加。通过 PET 或脑脊液分析测量的 FDG-PET 和淀粉样蛋白水平上的生物标志物关系最强。在神经病理学上，焦虑随着早期 Braak 阶段 tau 蛋白病理学的出现而出现。载脂蛋白 E e4 等位基因的存在与各个阶段的焦虑增加有关，尤其是在轻度认知障碍时。焦虑预示着痴呆症前期的所有阶段都进展得更快。

结论：这项工作表明焦虑和 AD 之间存在密切的生物学关系，这种关系从早期就开始并影响功能衰退。因此，我们讨论未来的工作，以提高我们对这种关系的理解，并测试抗焦虑治疗作为 AD 疾病修饰疗法的有效性。