Cognitive and immunological effects of yoga compared to memory training in older women at risk for alzheimer's disease

Abstract

Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) accompanied by cerebrovascular risk factors (CVRFs) are known to increase the risk of developing dementia. Mind-body practices such as yoga and meditation, have been recognized as safe techniques with beneficial effects on cognitive functions in older adults at risk for cognitive decline. We conducted a randomized, controlled trial to assess the efficacy of Kundalini yoga training (KY) compared to memory enhancement training (MET) on mood and cognitive functioning in a group of older women with CVRFs and SCD (clinicaltrials.gov = NCT03503669). The KY intervention consisted of weekly, 60-min in-person classes with a certified instructor for 12 weeks, with a 12-min guided recording for daily homework practice at home. MET involved 12 weekly in-person group classes with 12-min daily homework exercises. Objective and subjective memory performance were the primary outcomes. Peripheral whole blood samples were collected at baseline, 12-weeks, and 24-weeks follow-up for RNA sequencing and cytokine/chemokine assays. A total of 79 patients (KY = 40; MET = 39) were randomized, and 63 completed the 24-week follow-up (KY = 65% completion rate; MET = 95%; χ2(1) = 10.9, p < 0.001). At 24-weeks follow-up, KY yielded a significant, large effect size improvement in subjective cognitive impairment measures compared to MET. KYOn a transcriptional level, at 12- and 24-week follow-up, KY uniquely altered aging-associated signatures, including interferon gamma and other psycho-neuro-immune pathways. Levels of chemokine eotaxin-1, an aging marker, increased over time in MET but not KY participants. These results suggest clinical and biological benefits to KY for SCD, linking changes in cognition to the anti-inflammatory effects of yoga.

Fig. 1. Weighted Gene Co-expression Network Analysis (WGCNA) to characterize module-trait relationships to baseline clinical outcome measures.

A Scale-free topology criterion plots show the scale independence (left) and mean connectivity (right) of the signed network as functions of the soft-thresholding power. The chosen soft-thresholding power (β) is indicated by a horizontal dashed line, which ensures scale independence above 0.8 and minimum mean connectivity. B Cluster dendrogram of the genes, with branches color-coded to represent distinct modules identified by the dynamic tree cut method. The horizontal dashed line represents the threshold for merging modules with a dissimilarity of less than 0.2. C Heatmap of module-trait relationships, with each cell displaying the correlation coefficient (Pearson’s r) between the module eigengene and the specific trait (columns). The color gradient ranges from green (negative correlation) to red (positive correlation), with a color key and correlation values provided in each cell. Statistically significant relationships (p < 0.1) are marked with an asterisk (*). D Over-representation analysis for Module 3, with the x-axis showing the -log10(adjusted p-value) and the y-axis displaying the top enriched pathways. The horizontal dashed line indicates the significance threshold at adjusted p-value < 0.05.

Fig. 2. Identification of genes with discordant expression following KY and MET at 12- and 24-weeks enriched for aging signatures.

A Stratified Rank-Rank Hypergeometric Overlap (RRHO) result map illustrating the statistical significance of the overlap between KY 12-week follow-up versus baseline and MET 12-week follow-up versus baseline. The color gradient represents the -log10 (p-value) of the hypergeometric test, with warmer colors indicating higher significance. The x- and y-axes correspond to the ranked gene lists. Signal in the upper left quadrant and low right quadrant indicates discordant expression (e.g., upregulated in one-dataset and down-regulated in the other). Signal in the upper right quadrant and lower left quadrant (greyed out) represent areas of expression overlap (e.g., upregulated or downregulated in both datasets). B, C Over-representation analyses of Genotype-Tissue Expression (GTEx) blood aging signatures using discordant genes, where expression is upregulated in KY and downregulated in MET at 12-week follow-up, or vice versa. The x-axis denotes the -log10(adjusted p-value) of the analysis result. The red dashed line represents the threshold for statistical significance (adjusted p-value < 0.05). D Stratified Rank-Rank Hypergeometric Overlap (RRHO) result map illustrating the statistical significance of the overlap between KY 24-week follow-up versus baseline and MET 24-week follow-up versus baseline. E, F Over-representation analysis of Genotype-Tissue Expression (GTEx) blood aging signatures using discordant genes, where expression is upregulated in KY and downregulated in MET at 24-week follow-up, or vice versa.