Impact of Short-Term Mindful Awareness Practice on Kynurenine Pathway Regulation in Mild Cognitive Impairment: A Pilot Study.

Abstract

Mild cognitive impairment (MCI) is a high-risk prodromal state for Alzheimer's disease (AD). Its progression to AD is influenced by psychological distress, stress, anxiety, and depression, and kynurenine pathway (KP) dysregulation. Mindfulness-based interventions are proven to alleviate negative emotions; however, their impact on neuroinflammatory KP is unknown. This study determined the impact of short-term mindful awareness practice (MAP) on the serum KP profile and its associated modifiable risk factors for slow disease progression in MCI individuals. This was a 21-day pilot randomized controlled trial. Patients with MCI (Montreal Cognitive Assessment score: 18-25) were randomized to a MAP group (n = 17, 66.7 ± 6.6 years) receiving 30 min of daily guided practice, or a control group (n = 19, 69.2 ± 8.7 years) receiving familiar support. Serum kynurenines and inflammatory markers were measured at baseline (day 0) and post-intervention (day 21). The MAP group showed significant decreases in serum tryptophan (p < 0.05) and kynurenine (p < 0.01), with an increase in pro-inflammatory interferon-gamma (p < 0.05). No significant changes were found for negative emotions, cortisol, or other kynurenines, including neuroprotective picolinic acid, neurotoxic 3-hydroxykynurenine, and quinolinic acid. Concurrently, the control group demonstrated similar changes, with significant changes in cortisol (p < 0.01). This pilot study highlights a complex relationship between short-term MAP, the KP, and the immune system in MCI. The findings suggest a need for longer durations or higher intensities of practice in the MCI cohort. Future longitudinal research with a larger sample size is strongly recommended to validate these preliminary results.