Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150 Vienna, Austria.
Int J Mol Sci. 2021 Dec 28;23(1):308. doi: 10.3390/ijms23010308.
Depression in older individuals is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, associated with high disability, cognitive decline, and increased mortality The factors predicting the risk of late-life depression (LLD) are incompletely understood. The reciprocal relationship of depressive disorder and age- and disease-related processes has generated pathogenic hypotheses and provided various treatment options. The heterogeneity of depression complicates research into the underlying pathogenic cascade, and factors involved in LLD considerably differ from those involved in early life depression. Evidence suggests that a variety of vascular mechanisms, in particular cerebral small vessel disease, generalized microvascular, and endothelial dysfunction, as well as metabolic risk factors, including diabetes, and inflammation that may induce subcortical white and gray matter lesions by compromising fronto-limbic and other important neuronal networks, may contribute to the development of LLD. The "vascular depression" hypothesis postulates that cerebrovascular disease or vascular risk factors can predispose, precipitate, and perpetuate geriatric depression syndromes, based on their comorbidity with cerebrovascular lesions and the frequent development of depression after stroke. Vascular burden is associated with cognitive deficits and a specific form of LLD, vascular depression, which is marked by decreased white matter integrity, executive dysfunction, functional disability, and poorer response to antidepressive therapy than major depressive disorder without vascular risk factors. Other pathogenic factors of LLD, such as neurodegeneration or neuroimmune regulatory dysmechanisms, are briefly discussed. Treatment planning should consider a modest response of LLD to antidepressants, while vascular and metabolic factors may provide promising targets for its successful prevention and treatment. However, their effectiveness needs further investigation, and intervention studies are needed to assess which interventions are appropriate and effective in clinical practice.
老年人的抑郁症是一种常见的复杂情绪障碍，与精神和身体疾病的高共病率有关，与高残疾、认知能力下降和死亡率增加有关。预测老年抑郁症（LLD）风险的因素尚不完全清楚。抑郁障碍与年龄和疾病相关过程的相互关系产生了发病假说，并提供了各种治疗选择。抑郁症的异质性使对潜在发病级联的研究变得复杂，LLD 涉及的因素与生命早期抑郁症涉及的因素有很大不同。有证据表明，多种血管机制，特别是脑小血管疾病、广泛的微血管和内皮功能障碍，以及代谢危险因素，包括糖尿病和炎症，可能通过损害额 - 边缘和其他重要神经元网络，导致 subcortical 白质和灰质损伤，从而导致 LLD 的发展。“血管性抑郁”假说假设，基于脑血管疾病或血管危险因素与脑血管病变的共病以及中风后抑郁的频繁发生，它们可能使老年抑郁综合征易患、引发和持续存在。血管负担与认知缺陷和一种特定形式的 LLD（血管性抑郁症）有关，其特征是白质完整性下降、执行功能障碍、功能障碍以及对抗抑郁治疗的反应较差，而没有血管危险因素的重性抑郁症则反应较好。LLD 的其他发病因素，如神经退行性变或神经免疫调节失调机制，也有简要讨论。治疗计划应考虑到 LLD 对抗抑郁药的适度反应，而血管和代谢因素可能为其成功预防和治疗提供有希望的靶点。然而，它们的有效性需要进一步研究，并且需要干预研究来评估哪些干预措施在临床实践中是适当和有效的。
