vmPFC's role in adherence to cognitive training

认知训练被认为是减缓认知老化和AD/ADRD的一种有前景的非药物干预手段。如果我们要了解干预的机制，以及最大限度地从干预中减缓甚至防止AD/ADRD认知能力下降和进展的长期效益，确保坚持是必不可少的。基于视觉的加工速度（VSOP）训练已成为预防认知衰老的一线认知训练策略之一，本研究旨在探讨基于视觉的加工速度（VSOP）训练方案依从性的作用机制。我们的中心假设是，通过既定的共振频率呼吸（RFB）训练来加强腹内侧前额叶皮层（vmPFC）功能，将导致更强的VSOP训练依从性，反映在更大的参与和更多的使用VSOP训练计划在规定的干预期间和之后的几个月。我们将应用一个已建立的、心理疲劳的多维框架来衡量认知训练的有效参与。我们在0期机制干预研究中提出了3组比较：遗忘性轻度认知障碍（MCI）的RFB，临床前AD/ADRD阶段（MCI, n = 31），健康对照组（HC, n = 31）的RFB，以及MCI的图像引导放松（IR）对照组（n = 31）。所有参与者将参加为期8周的家庭VSOP培训，并在干预后3个月和9个月提供两次为期2周的强化课程。RFB或IR将在每次VSOP培训之前立即进行练习，包括规定的和加强的课程。目的是确定RFB干预在依从性中的作用（目的1）；检查vmPFC功能与依从性之间的关系（目的2）；并建立长期依从性的个性化预测模型（探索性目标3）。与认知训练的神经认知效应相比，如何确保依从性是AD/ADRD预防策略发展中尚未研究的主题，这与AD/ADRD研究里程碑8.B中描述的研究计划相一致。该研究将为如何全面测量依从性、依从性机制和潜在的干预策略提供新的机制和临床相关信息，以提高对减缓或预防AD/ADRD干预措施的依从性。

Cognitive training is considered a promising non-pharmacologic intervention for slowing cognitive aging and AD/ADRD. Ensuring adherence is essential if we are to understand the mechanisms of intervention, as well as to maximize long-term benefits from intervention in slowing or even preventing cognitive decline and progression of AD/ADRD. The objective of the proposed R61 is to examine the mechanisms of action underlying adherence to prescribed regimens of the vision-based speed of processing (VSOP) training, which has been among the first-line cognitive training preventative strategies for cognitive aging. Our central hypothesis is that strengthening the ventromedial prefrontal cortex (vmPFC) function, via an established resonance frequency breathing (RFB) training, will lead to greater adherence to VSOP training, reflected in greater engagement with and more use of the VSOP training program during and in the months following the prescribed intervention period. We will apply an established, multi-dimensional framework of mental fatigability for measuring effective engagement in cognitive training. We propose a 3-group comparison in a stage 0 mechanistic intervention study: RFB in amnestic mild cognitive impairment (MCI), a preclinical stage of AD/ADRD (MCI, n = 31), RFB in healthy control (HC, n = 31), and an imagery-guided relaxation (IR) control in MCI (n = 31). All participants will engage in an 8-week prescribed home-based VSOP training and two 2-week booster sessions provided at 3- and 9-months after intervention. RFB or IR will be practiced immediately before every VSOP training during the prescribed and booster sessions. The aims are to identify the role of RFB intervention in adherence (Aim 1); examine the relationship between the vmPFC function and adherence (Aim 2); and build a personalized predictive model for long-term adherence (exploratory Aim 3). Compared to neurocognitive effects of cognitive training, how to ensure adherence is an understudied topic in the development of prevention strategies for AD/ADRD, which aligns with research plans described in AD/ADRD Research Milestone 8.B. The proposed study will provide novel mechanistic and clinically relevant information on how to comprehensively measure adherence, the mechanism underlying adherence, and potential intervention strategies for enhancing adherence to interventions serving for slowing or preventing AD/ADRD.