Perus Lisa, Busto Germain U, Mangin Jean-François, Le Bars Emmanuelle, Gabelle Audrey
INM, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.
Department of Neurology, Memory Resources and Research Center, Gui de Chauliac Hospital, Montpellier, France.
Front Aging Neurosci. 2022 Nov 24;14:1014559. doi: 10.3389/fnagi.2022.1014559. eCollection 2022.
Alzheimer's Disease (AD) is a multifactorial and complex neurodegenerative disorder. Some modifiable risk factors have been associated with an increased risk of appearance of the disease and/or cognitive decline. Preventive clinical trials aiming at reducing one or combined risk factors have been implemented and their potential effects assessed on cognitive trajectories and on AD biomarkers. However, the effect of interventions on surrogate markers, in particular imaging biomarkers, remains poorly understood. We conducted a review of the literature and analyzed 43 interventional studies that included physical exercise, nutrition, cognitive training or multidomain interventions, and assessed various brain imaging biomarkers, to determine the effects of preventive interventions on imaging biomarkers for subjects at-risk to develop AD. Deciphering the global and regional brain effect of each and combined interventions will help to better understand the interplay relationship between multimodal interventions, cognition, surrogate brain markers, and to better design primary and secondary outcomes for future preventive clinical trials. Those studies were pondered using generally-admitted quality criteria to reveal that interventions may affect the brain of patients with cognitive impairment rather than those without cognitive impairment thus indicating that particular care should be taken when selecting individuals for interventions. Additionally, a majority of the studies concurred on the effect of the interventions and particularly onto the frontal brain areas.
阿尔茨海默病(AD)是一种多因素的复杂神经退行性疾病。一些可改变的风险因素与该疾病出现和/或认知衰退的风险增加有关。旨在降低一种或多种风险因素的预防性临床试验已经开展,并评估了它们对认知轨迹和AD生物标志物的潜在影响。然而,干预措施对替代标志物,特别是成像生物标志物的影响仍知之甚少。我们对文献进行了综述,并分析了43项干预性研究,这些研究包括体育锻炼、营养、认知训练或多领域干预,并评估了各种脑成像生物标志物,以确定预防性干预措施对有患AD风险的受试者成像生物标志物的影响。解读每种干预措施以及联合干预措施对大脑整体和区域的影响,将有助于更好地理解多模式干预、认知、替代脑标志物之间的相互作用关系,并为未来的预防性临床试验更好地设计主要和次要结果。使用普遍认可的质量标准对这些研究进行权衡后发现,干预措施可能会影响认知障碍患者的大脑,而不是无认知障碍患者的大脑,这表明在选择干预对象时应格外谨慎。此外,大多数研究在干预措施的效果上达成了共识,特别是对额叶脑区的影响。