vmPFC's role in adherence to cognitive training

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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.