Resistance exercise effects on hippocampus subfield volumes and biomarkers of neuroplasticity and neuroinflammation in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial.

Physical exercise is suggested to promote hippocampal neuroplasticity by increasing circulating neurotrophic and anti-inflammatory factors. Our aim was to explore the interplay between the effect of progressive resistance exercise on blood biomarker levels, hippocampal neurometabolite levels and hippocampal volume in older adults with a low compared to a high risk of mild cognitive impairment (MCI). Seventy apparently healthy male/female older adults (aged 60-85 years old) were randomly allocated to a 12 week lower limb progressive resistance or no intervention, stratified for low (< 26/30) or high (≥ 26/30) Montreal Cognitive Assessment (MoCA) score, indicating MCI risk. Outcome measures were blood levels of insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6) or kynurenine (KYN); hippocampal total and subfield volumes of the cornu ammonis 1 (CA1) and 4 (CA4), subiculum, presubiculum, and dentate gyrus measured with magnetic resonance imaging (MRI); and hippocampus neurometabolites including total N-acetylaspartate (NAA), myo-inositol (mIns), and total creatine (Cr) measured with proton magnetic resonance spectroscopy (H-MRS). We evaluated the intervention effect, cognitive status effect, their interaction and the bivariate relationship between exercise-induced changes between the outcome measures. Higher kynurenine levels (p = 0.015) and lower subiculum volumes (p = 0.043) were found in older adults with high MCI risk compared to older adults with low MCI risk. Exercise-induced CA1 volume changes were negatively correlated with hippocampal tNAA/mIns level changes (r = -0.605, p = 0.006). This study provides valuable insight in the multifactorial processes related to resistance training in older adults with low or high MCI risk.