Comprehensive Center for Brain Health, Department of Neurology, University of Miami Miller School of Medicine, Boca Raton, FL, USA.
J Alzheimers Dis. 2022;90(2):461-473. doi: 10.3233/JAD-220755.
With the expected rise in Alzheimer's disease and related dementias (ADRD) in the coming decades due to the aging population and a lack of effective disease-modifying treatments, there is a need for preventive strategies that may tap into resilience parameters. A wide array of resilience strategies has been proposed including genetics, socioeconomic status, lifestyle modifications, behavioral changes, and management of comorbid disease. These different strategies can be broadly classified as distinguishing between modifiable and non-modifiable risk factors, some of which can be quantified so that their clinical intervention can be effectively accomplished. A clear shift in research focus from dementia risk to addressing disease resistance and resilience is emerging that has provided new potential therapeutic targets. Here we review and summarize the latest investigations of resilience mechanisms and methods of quantifying resilience for clinical research. These approaches include identifying genetic variants that may help identify novel pathways (e.g., lipid metabolism, cellular trafficking, synaptic function, inflammation) for therapeutic treatments and biomarkers for use in a precision medicine-like regimen. In addition, innovative structural and molecular neuroimaging analyses may assist in detecting and quantifying pathological changes well before the onset of clinical symptoms setting up the possibility of primary and secondary prevention trials. Lastly, we summarize recent studies demonstrating the study of resilience in caregivers of persons living with dementia may have direct and indirect impact on the quality of care and patient outcomes.
由于人口老龄化和缺乏有效的疾病修饰治疗,预计在未来几十年阿尔茨海默病和相关痴呆症(ADRD)的发病率将会上升,因此需要预防策略,这些策略可能利用到韧性参数。已经提出了广泛的韧性策略,包括遗传学、社会经济地位、生活方式的改变、行为的改变以及共病的管理。这些不同的策略可以大致分为可改变和不可改变的风险因素,其中一些可以量化,以便有效地进行临床干预。研究重点从痴呆风险向抵抗和韧性的转变已经出现,这为新的潜在治疗靶点提供了新的可能。在这里,我们回顾和总结了韧性机制和韧性量化的最新研究,这些方法包括识别可能有助于确定治疗新途径(例如,脂质代谢、细胞运输、突触功能、炎症)的遗传变异,以及用于精准医疗样方案的生物标志物。此外,创新的结构和分子神经影像学分析可能有助于在临床症状出现之前检测和量化病理变化,为初级和二级预防试验创造了可能。最后,我们总结了最近的研究,这些研究表明对痴呆患者护理者的韧性研究可能对护理质量和患者预后有直接和间接的影响。