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

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.

Impact of Yoga Versus Memory Enhancement Training on Hippocampal Connectivity in Older Women at Risk for Alzheimer's Disease.

BACKGROUND: Yoga may be an ideal early intervention for those with modifiable risk factors for Alzheimer's disease (AD) development. OBJECTIVE: To examine the effects of Kundalini yoga (KY) training versus memory enhancement training (MET) on the resting-state connectivity of hippocampal subregions in women with subjective memory decline and cardiovascular risk factors for AD. METHODS: Participants comprised women with subjective memory decline and cardiovascular risk factors who participated in a parent randomized controlled trial (NCT03503669) of 12-weeks of KY versus MET and completed pre- and post-intervention resting-state magnetic resonance imaging scans (yoga: n = 11, age = 61.45±6.58 years; MET: n = 11, age = 64.55±6.41 years). Group differences in parcellated (Cole-anticevic atlas) hippocampal connectivity changes (post- minus pre-intervention) were evaluated by partial least squares analysis, controlling for age. Correlations between hippocampal connectivity and perceived stress and frequency of forgetting (assessed by questionnaires) were also evaluated. RESULTS: A left anterior hippocampal subregion assigned to the default mode network (DMN) in the Cole-anticevic atlas showed greater increases in connectivity with largely ventral visual stream regions with KY than with MET (p < 0.001), which showed associations with lower stress (p < 0.05). Several posterior hippocampal subregions assigned to sensory-based networks in the Cole-anticevic atlas showed greater increases in connectivity with regions largely in the DMN and frontoparietal network with MET than with KY (p < 0.001), which showed associations with lower frequency of forgetting (p < 0.05). CONCLUSION: KY training may better target stress-related hippocampal connectivity, whereas MET may better target hippocampal sensory-integration supporting better memory reliability, in women with subjective memory decline and cardiovascular risk factors.

Yoga Prevents Gray Matter Atrophy in Women at Risk for Alzheimer's Disease: A Randomized Controlled Trial.

BACKGROUND: Female sex, subjective cognitive decline (SCD), and cardiovascular risk factors (CVRFs) are known risk factors for developing Alzheimer's disease (AD). We previously demonstrated that yoga improved depression, resilience, memory and executive functions, increased hippocampal choline concentrations, and modulated brain connectivity in older adults with mild cognitive impairment. OBJECTIVE: In this study (NCT03503669), we investigated brain gray matter volume (GMV) changes in older women with SCD and CVRFs following three months of yoga compared to memory enhancement training (MET). METHODS: Eleven women (mean age = 61.45, SD = 6.58) with CVRF and SCD completed twelve weeks of Kundalini Yoga and Kirtan Kriya (KY + KK) while eleven women (mean age = 64.55, SD = 6.41) underwent MET. Anxiety, resilience, stress, and depression were assessed at baseline and 12 weeks, as were T1-weighted MRI scans (Siemens 3T Prisma scanner). We used Freesurfer 6.0 and tested group differences in GMV change, applying Monte-Carlo simulations with alpha = 0.05. Region-of-interest analysis was performed for hippocampus and amygdala. RESULTS: Compared to KY + KK, MET showed reductions in GMV in left prefrontal, pre- and post-central, supramarginal, superior temporal and pericalcarine cortices, right paracentral, postcentral, superior and inferior parietal cortices, the banks of the superior temporal sulcus, and the pars opercularis. Right hippocampal volume increased after yoga but did not survive corrections. CONCLUSION: Yoga training may offer neuroprotective effects compared to MET in preventing neurodegenerative changes and cognitive decline, even over short time intervals. Future analyses will address changes in functional connectivity in both groups.

A randomized controlled trial of Kundalini yoga in mild cognitive impairment.

BACKGROUND: Global population aging will result in increasing rates of cognitive decline and dementia. Thus, effective, low-cost, and low side-effect interventions for the treatment and prevention of cognitive decline are urgently needed. Our study is the first to investigate the effects of Kundalini yoga (KY) training on mild cognitive impairment (MCI). METHODS: Older participants (≥55 years of age) with MCI were randomized to either a 12-week KY intervention or memory enhancement training (MET; gold-standard, active control). Cognitive (i.e. memory and executive functioning) and mood (i.e. depression, apathy, and resilience) assessments were administered at baseline, 12 weeks and 24 weeks. RESULTS: At baseline, 81 participants had no significant baseline group differences in clinical or demographic characteristics. At 12 weeks and 24 weeks, both KY and MET groups showed significant improvement in memory; however, only KY showed significant improvement in executive functioning. Only the KY group showed significant improvement in depressive symptoms and resilience at week 12. CONCLUSION: KY group showed short- and long-term improvements in executive functioning as compared to MET, and broader effects on depressed mood and resilience. This observation should be confirmed in future clinical trials of yoga intervention for treatment and prevention of cognitive decline (NCT01983930).

Changes in Neural Connectivity and Memory Following a Yoga Intervention for Older Adults: A Pilot Study.

BACKGROUND: No study has explored the effect of yoga on cognitive decline and resting-state functional connectivity. OBJECTIVES: This study explored the relationship between performance on memory tests and resting-state functional connectivity before and after a yoga intervention versus active control for subjects with mild cognitive impairment (MCI). METHODS: Participants ( ≥ 55 y) with MCI were randomized to receive a yoga intervention or active "gold-standard" control (i.e., memory enhancement training (MET)) for 12 weeks. Resting-state functional magnetic resonance imaging was used to map correlations between brain networks and memory performance changes over time. Default mode networks (DMN), language and superior parietal networks were chosen as networks of interest to analyze the association with changes in verbal and visuospatial memory performance. RESULTS: Fourteen yoga and 11 MET participants completed the study. The yoga group demonstrated a statistically significant improvement in depression and visuospatial memory. We observed improved verbal memory performance correlated with increased connectivity between the DMN and frontal medial cortex, pregenual anterior cingulate cortex, right middle frontal cortex, posterior cingulate cortex, and left lateral occipital cortex. Improved verbal memory performance positively correlated with increased connectivity between the language processing network and the left inferior frontal gyrus. Improved visuospatial memory performance correlated inversely with connectivity between the superior parietal network and the medial parietal cortex. CONCLUSION: Yoga may be as effective as MET in improving functional connectivity in relation to verbal memory performance. These findings should be confirmed in larger prospective studies.

Yogic meditation reverses NF-κB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial.

BACKGROUND: Although yoga and meditation have been used for stress reduction with reported improvement in inflammation, little is known about the biological mechanisms mediating such effects. The present study examined if a yogic meditation might alter the activity of inflammatory and antiviral transcription control pathways that shape immune cell gene expression. METHODS: Forty-five family dementia caregivers were randomized to either Kirtan Kriya Meditation (KKM) or Relaxing Music (RM) listening for 12 min daily for 8 weeks and 39 caregivers completed the study. Genome-wide transcriptional profiles were collected from peripheral blood leukocytes sampled at baseline and 8-week follow-up. Promoter-based bioinformatics analyses tested the hypothesis that observed transcriptional alterations were structured by reduced activity of the pro-inflammatory nuclear factor (NF)-κB family of transcription factors and increased activity of Interferon Response Factors (IRFs; i.e., reversal of patterns previously linked to stress). RESULTS: In response to KKM treatment, 68 genes were found to be differentially expressed (19 up-regulated, 49 down-regulated) after adjusting for potentially confounded differences in sex, illness burden, and BMI. Up-regulated genes included immunoglobulin-related transcripts. Down-regulated transcripts included pro-inflammatory cytokines and activation-related immediate-early genes. Transcript origin analyses identified plasmacytoid dendritic cells and B lymphocytes as the primary cellular context of these transcriptional alterations (both p<.001). Promoter-based bioinformatic analysis implicated reduced NF-κB signaling and increased activity of IRF1 in structuring those effects (both p<.05). CONCLUSION: A brief daily yogic meditation intervention may reverse the pattern of increased NF-κB-related transcription of pro-inflammatory cytokines and decreased IRF1-related transcription of innate antiviral response genes previously observed in healthy individuals confronting a significant life stressor.

A pilot study of the effects of meditation on regional brain metabolism in distressed dementia caregivers.

AIMS: Caregiver distress can affect mood and cognition. Meditation can be used to reduce stress. This pilot study explored whether yogic meditation could change regional cerebral metabolism in distressed caregivers. METHODS: Nine dementia caregivers were randomized to undergo meditation training compared with relaxation for 12 min per day for 8 weeks. Caregivers received neuropsychiatric assessments and brain FDG-PET scans at baseline and postintervention. RESULTS: The groups did not differ on measures of mood, mental and physical health, and burden at baseline and follow-up. When comparing the regional cerebral metabolism between groups, significant differences over time were found in the bilateral cerebellum (p < 0.0005), right inferior lateral anterior temporal (p < 0.0005), right inferior frontal (p = 0.001), left superior frontal (p = 0.001), left associative visual (p = 0.002) and right posterior cingulate (p = 0.002) cortices. CONCLUSION: Meditation practice in distressed caregivers resulted in different patterns of regional cerebral metabolism from relaxation. These pilot results should be replicated in a larger study.

Cerebral blood flow differences between long-term meditators and non-meditators.

We have studied a number of long-term meditators in previous studies. The purpose of this study was to determine if there are differences in baseline brain function of experienced meditators compared to non-meditators. All subjects were recruited as part of an ongoing study of different meditation practices. We evaluated 12 advanced meditators and 14 non-meditators with cerebral blood flow (CBF) SPECT imaging at rest. Images were analyzed with both region of interest and statistical parametric mapping. The CBF of long-term meditators was significantly higher (p<.05) compared to non-meditators in the prefrontal cortex, parietal cortex, thalamus, putamen, caudate, and midbrain. There was also a significant difference in the thalamic laterality with long-term meditators having greater asymmetry. The observed changes associated with long-term meditation appear in structures that underlie the attention network and also those that relate to emotion and autonomic function.

Meditation effects on cognitive function and cerebral blood flow in subjects with memory loss: a preliminary study.

This preliminary study determined if subjects with memory loss problems demonstrate changes in memory and cerebral blood flow (CBF) after a simple 8-week meditation program. Fourteen subjects with memory problems had an IV inserted and were injected with 250 MBq of Tc-99m ECD while listening to a neutral stimulus CD. They then underwent a pre-program baseline SPECT scan. Then subjects were guided through their first meditation session with a CD, during which they received an injection of 925 MBq ECD, and underwent a pre-program meditation scan. Subjects completed an 8-week meditation program and underwent the same scanning protocol resulting in a post-program baseline and meditation scan. A region of interest (ROI) template obtained counts in each ROI normalized to whole brain to provide a CBF ratio. Baseline and meditation scans and neuropsychological testing were compared before and after the program. The meditation program resulted in significant increases (p< 0.05) in baseline CBF ratios in the prefrontal, superior frontal, and superior parietal cortices. Scores on neuropsychological tests of verbal fluency, Trails B, and logical memory showed improvements after training. This preliminary study evaluated whether an 8-week meditation program resulted in improvements in neuropsychological function and differences in CBF in subjects with memory loss. While the findings are encouraging, there are a number of limitations that can be addressed in future studies with more participants and more detailed analyses.