Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, 116021, China.
Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
Front Med. 2024 Jun;18(3):446-464. doi: 10.1007/s11684-023-1047-1. Epub 2024 May 21.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions. The disease follows a continuum, starting with preclinical stages, progressing to mild cognitive and behavioral impairment, ultimately leading to dementia. Early detection of AD is crucial for better diagnosis and more effective treatment. However, the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive, and mostly are still not able to detect early disease state. Consequently, there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of AD. Various non-cognitive manifestations, including behavioral abnormalities, sleep disturbances, sensory dysfunctions, and physical changes, have been observed in the preclinical AD stage before occurrence of notable cognitive decline. Recent research advances have identified several biofluid biomarkers as early indicators of AD. This review focuses on these non-cognitive changes and newly discovered biomarkers in AD, specifically addressing the preclinical stages of the disease. Furthermore, it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,影响认知和非认知功能。该疾病呈连续谱,从临床前阶段开始,进展为轻度认知和行为障碍,最终导致痴呆。早期发现 AD 对于更好的诊断和更有效的治疗至关重要。然而,目前使用脑脊液和/或脑成像的 AD 生物标志物诊断测试具有侵入性或昂贵,并且大多仍然无法检测到早期疾病状态。因此,迫切需要在 AD 的临床前阶段开发具有更高灵敏度和特异性的新诊断技术。在认知能力显著下降之前,在临床前 AD 阶段已经观察到各种非认知表现,包括行为异常、睡眠障碍、感觉功能障碍和身体变化。最近的研究进展已经确定了几种生物流体生物标志物作为 AD 的早期指标。本综述重点介绍 AD 中的这些非认知变化和新发现的生物标志物,特别是针对疾病的临床前阶段。此外,探索开发预测系统或网络以在 AD 的早期阶段预测疾病发作和进展的潜力也很重要。