Comparative efficacy of seven nonpharmacological interventions on global cognition in older adults with and without mild cognitive impairment: a network meta-analysis of randomized controlled trials.

To maintain current cognitive function and access greater cognitive reserves, nonpharmacological interventions may be a viable alternative for older adults with or without cognitive impairment. This study aimed to compare different nonpharmacological interventions for enhancing global cognition, including mind-body exercise, physical exercise, non-invasive brain stimulation, cognitive training intervention (CTI), acutherapy (ACU), meditation, and music therapy, by applying a network meta-analysis (NMA). Sixty-one randomized controlled trials evaluating the efficacy of interventions on global cognition in older adults with or without mild cognitive decline were selected. An NMA was conducted to compare the efficacy of different nonpharmacological interventions. The NMA revealed that mind-body exercise (standardized mean difference, 1.384; 95% confidence interval, 0.777-1.992); ACU (1.283; 0.478-2.088); meditation (0.910; 0.097-1.724); non-invasive brain stimulation (1.242; 0.254-2.230); CTI (1.269; 0.736-1.802); and physical exercise (0.977; 0.212-1.742), showed positive effects compared to passive controls. There were no significant differences between the efficacies of other interventions. Nonpharmacological interventions may potentially enhance and maintain global cognition through various pathways, such as memorizing movements and enhancing brain plasticity by reducing stress in the older adult population. Additional studies are needed to clarify the impact of other variables, including intervention methods or psychological variables.

The Mediating Role of Cortical Atrophy on the Relationship between the Resilience Index and Cognitive Function: Findings from the Healthy Brain Initiative.

Background: Lifestyle factors are linked to differences in brain aging and risk for Alzheimer's disease, underscored by concepts like 'cognitive reserve' and 'brain maintenance'. The Resilience Index (RI), a composite of 6 factors (cognitive reserve, physical and cognitive activities, social engagement, diet, and mindfulness) provides such a holistic measure. Objective: This study aims to examine the association of RI scores with cognitive function and assess the mediating role of cortical atrophy. Methods: Baseline data from 113 participants (aged 45+, 68% female) from the Healthy Brain Initiative were included. Life course resilience was estimated with the RI, cognitive performance with Cognivue®, and brain health using a machine learning derived Cortical Atrophy Score (CAS). Mediation analysis probed the relationship between RI, cognitive outcomes, and cortical atrophy. Results: In age and sex adjusted models, the RI was significantly associated with CAS (ß= -0.25, p = 0.006) and Cognivue® scores (ß= 0.32, p < 0.001). The RI-Cognivue® association was partially mediated by CAS (ß= 0.07; 95% CI [0.02, 0.14]). Conclusions: Findings revealed that the collective effect of early and late-life lifestyle resilience factors on cognition are partially explained by their association with less brain atrophy. These findings underscore the value of comprehensive lifestyle assessments in understanding the risk and progression of cognitive decline and Alzheimer's disease in an aging population.

A qualitative exploration of 40 Hz sound and music for older adults with mild cognitive impairment.

Emerging evidence suggests that 40 Hz auditory stimulation may benefit cognition. Nested within a randomized crossover trial, this qualitative study evaluates the acceptability and experience of three auditory interventions-self-selected music, 40 Hz sound, and a novel combination, termed 40 Hz music-in individuals with Mild Cognitive Impairment (MCI). Semi-structured interviews were conducted with individuals with MCI post-intervention exposure. Findings indicated a preference for self-selected music due to its memory-boosting and emotional benefits, while responses to 40 Hz sound were mixed, with several participants reporting discomfort. The composite 40 Hz music intervention showed promise, striking a balance by enhancing user experience and mitigating the 40 Hz sound's negative aspects. Engagement was influenced by personal music interests, listening routines, and support networks. This study highlights the potential of integrating 40 Hz sound with personalized music to offer a more acceptable 40 Hz auditory intervention for cognition in older adults with MCI.

Predictive deep learning models for cognitive risk using accessible data.

The early detection of mild cognitive impairment (MCI) is crucial to preventing the progression of dementia. However, it necessitates that patients voluntarily undergo cognitive function tests, which may be too late if symptoms are only recognized once they become apparent. Recent advances in deep learning have improved model performance, leading to applied research in various predictive problems. Studies attempting to estimate dementia and the risk of MCI based on readily available data are being conducted, with the hope of facilitating the early detection of MCI. The data used for these predictions vary widely, including facial imagery, voice recordings, blood tests, and inertial information during walking. Deep learning models that make predictions based on these data sources have been proposed. This article summarizes recent research efforts to predict the risk of dementia using easily accessible data. As research progresses and more accurate predictions become feasible, simple tests could be incorporated into daily life to monitor one's personal health status and to facilitate an early intervention.

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.

Hypnosis Intervention for Sleep Disturbances in Individuals with Mild Cognitive Impairment: A Randomized Pilot Study.

Poor sleep quality is highly prevalent among individuals with mild cognitive impairment (MCI). Further, poor sleep quality is associated with reduced quality of life, increased stress response, memory impairments, and progression to dementia among individuals with MCI. Pharmacological treatments for sleep have mixed efficacy and can lead to dependency. Therefore, alternatives to pharmacological treatments for improving sleep among individuals with MCI are needed. The present study reports on the feasibility of a non-pharmacological self-administered hypnosis intervention focused on sleep quality in adults with MCI. It was hypothesized that the hypnosis intervention program would be feasible and have acceptable levels of adherence to daily hypnosis practice. A two-armed randomized controlled pilot trial was conducted using a sample of 21 adults with MCI. Eligible participants were randomly assigned to listen to either hypnosis audio recordings or sham hypnosis recordings for five weeks. Program feasibility, program adherence, pain intensity, stress, and sleep quality were measured using a daily home practice log, questionnaires, and wrist actigraphy. The results found mid or higher levels of treatment satisfaction, ease of use, and perceived effectiveness at one-week follow-up, with participants in the hypnosis arm reporting greater perceived benefit. Adherence to assigned audio recordings and meetings were likewise within acceptable margins in both groups. No intervention-related adverse events were reported in either treatment condition. Significant improvements in sleep quality, sleep duration, and daytime sleepiness were found for the hypnosis intervention. The results of this study can be used to inform future research on the effects of hypnosis on sleep quality in adults with MCI.

The effect of receptive music therapy on older adults with mild cognitive impairment and depression: a randomized controlled trial.

This study aims to evaluate the effects of a receptive music therapy intervention on cognitive functions and depressive symptoms in older adults with MCI. A randomized controlled trial was conducted in Wuhan, China. Eighty older adults, over 65, who had MCI and depression symptoms were randomly divided into the intervention and control groups. The intervention group received usual nursing care plus receptive music therapy intervention four times a week, for eight weeks; the control group received usual nursing care during the same period. The linear regression analysis was used to compare the difference between groups. There was a significant difference in the intervention group for the pre-intervention and post-intervention scores of cognitive function and depression. There was no significant difference in the control group before and after the study period and a significant between-group difference in both cognitive function and depression. In conclusion, receptive music therapy intervention significantly improved cognitive function and reduced depressive symptoms in older adults with MCI. It could be widely used in communities and nursing homes to improve the quality of life of older adults.

Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Exercise, cognitive training, and vitamin D may enhance cognition in older adults with mild cognitive impairment (MCI). Objective: To determine whether aerobic-resistance exercises would improve cognition relative to an active control and if a multidomain intervention including exercises, computerized cognitive training, and vitamin D supplementation would show greater improvements than exercise alone. Design, Setting, and Participants: This randomized clinical trial (the SYNERGIC Study) was a multisite, double-masked, fractional factorial trial that evaluated the effects of aerobic-resistance exercise, computerized cognitive training, and vitamin D on cognition. Eligible participants were between ages 65 and 84 years with MCI enrolled from September 19, 2016, to April 7, 2020. Data were analyzed from February 2021 to December 2022. Interventions: Participants were randomized to 5 study arms and treated for 20 weeks: arm 1 (multidomain intervention with exercise, cognitive training, and vitamin D), arm 2 (exercise, cognitive training, and placebo vitamin D), arm 3 (exercise, sham cognitive training, and vitamin D), arm 4 (exercise, sham cognitive training, and placebo vitamin D), and arm 5 (control group with balance-toning exercise, sham cognitive training, and placebo vitamin D). The vitamin D regimen was a 10 000 IU dose 3 times weekly. Main Outcomes and Measures: Primary outcomes were changes in ADAS-Cog-13 and Plus variant at 6 months. Results: Among 175 randomized participants (mean [SD] age, 73.1 [6.6] years; 86 [49.1%] women), 144 (82%) completed the intervention and 133 (76%) completed the follow-up (month 12). At 6 months, all active arms (ie, arms 1 through 4) with aerobic-resistance exercise regardless of the addition of cognitive training or vitamin D, improved ADAS-Cog-13 when compared with control (mean difference, -1.79 points; 95% CI, -3.27 to -0.31 points; P = .02; d = 0.64). Compared with exercise alone (arms 3 and 4), exercise and cognitive training (arms 1 and 2) improved the ADAS-Cog-13 (mean difference, -1.45 points; 95% CI, -2.70 to -0.21 points; P = .02; d = 0.39). No significant improvement was found with vitamin D. Finally, the multidomain intervention (arm 1) improved the ADAS-Cog-13 score significantly compared with control (mean difference, -2.64 points; 95% CI, -4.42 to -0.80 points; P = .005; d = 0.71). Changes in ADAS-Cog-Plus were not significant. Conclusions and Relevance: In this clinical trial, older adults with MCI receiving aerobic-resistance exercises with sequential computerized cognitive training significantly improved cognition, although some results were inconsistent. Vitamin D supplementation had no effect. Our findings suggest that this multidomain intervention may improve cognition and potentially delay dementia onset in MCI. Trial Registration: ClinicalTrials.gov Identifier: NCT02808676.

Effects of home-based computerized cognitive training and tai chi exercise on cognitive functions in older adults with mild cognitive impairment.

BACKGROUND: A randomized trial was conducted to investigate the effects of computerized cognitive training (CCT) and tai chi exercise (TCE) vs. health education (HE) on cognitive functions in 189 older adults with mild cognitive impairment (MCI). METHODS: Cognitive functions were assessed by the five-domain Mattis Dementia Rating Scale (MDRS) (attention, initiation/perseveration, construction, conceptualization, and memory) and the modified Telephone Interview of Cognitive Status (TICS-M), while the timed up and go (TUG), Tinetti's balance, activities of daily living (ADLs), and Activities-specific Balance Confidence (ABC) were also evaluated. Each intervention was delivered once a week for 6 months. All outcomes were followed up at 6 and 12 months of the study. RESULTS: Compared to HE, CCT increased scores on the MDRS's total, initiation/perseveration, construction, and conceptualization domains and on the TICS-M at 6 months and those on the MDRS's total, attention, construction, conceptualization, and memory domains and on the TICS-M at 12 months; TCE increased scores on the MDRS's total and construction domains and on the TICS-M at 6 months and those on the MDRS's total, attention, initiation/perseveration, and conceptualization domains and on the TICS-M at 12 months. Moreover, CCT improved the TUG at 6 and 12 months and Tinetti's balance at 12 months, and TCE improved the TUG at 6 and 12 months, Tinetti's balance, and ABC at 6 and 12 months, and ADLs at 12 months. CONCLUSIONS: The effects of CCT and TCE on improving global cognition and certain cognitive domains for older MCI adults may have been small but they lasted for at least 12 months.

Observed Improvement in Cognition During a Personalized Lifestyle Intervention in People with Cognitive Decline.

BACKGROUND: Alzheimer's disease (AD) is a chronic condition marked by progressive objective cognitive impairment (OCI). No monotherapy has substantially altered disease progression, suggesting the disease is multifactorial and may require a multimodal therapeutic approach. OBJECTIVE: We sought to determine if cognitive function in a sample with OCI would change in response to a multimodal, individualized care plan based on potential contributors to cognitive decline (e.g., nutritional status, infection, etc.). METHODS: Participants (n = 34) were recruited from the San Diego, CA area. The multimodal intervention included lifestyle changes (i.e., movement, diet, and stress management), nutraceutical support, and medications. It was delivered pragmatically over four clinical visits, and outcome measures were gathered at four study visits, occurring at baseline, one, three, and six months (primary endpoint). Study participants received weekly phone calls for nutrition support throughout study participation. Outcome measures included the Cambridge Brain Sciences (CBS) battery, and the Montreal Cognitive Assessment (MoCA). RESULTS: At 6 months, mean MoCA scores improved from 19.6±3.1 to 21.7±6.2 (p = 0.013). Significant improvement was observed in mean scores of the CBS memory domain [25.2 (SD 23.3) to 35.8 (SD 26.9); p < 0.01] and CBS overall composite cognition score [24.5 (SD 16.1) to 29.7 (SD 20.5); p = 0.02]. All CBS domains improved. CONCLUSION: Multiple measures of cognitive function improved after six months of intervention. Our results support the feasibility and impact of a multimodal, individualized treatment approach to OCI, warranting further research.

Signatures of Neuropsychological Test Results in the Long Life Family Study: A Cluster Analysis.

BACKGROUND: Discovering patterns of cognitive domains and characterizing how these patterns associate with other risk factors and biomarkers can improve our understanding of the determinants of cognitive aging. OBJECTIVE: To discover patterns of cognitive domains using neuropsychological test results in Long Life Family Study (LLFS) and characterize how these patterns associate with aging markers. METHODS: 5,086 LLFS participants were administered neuropsychological tests at enrollment. We performed a cluster analysis of six baseline neuropsychological test scores and tested the association between the identified clusters and various clinical variables, biomarkers, and polygenic risk scores using generalized estimating equations and the Chi-square test. We used Cox regression to correlate the clusters with the hazard of various medical events. We investigated whether the cluster information could enhance the prediction of cognitive decline using Bayesian beta regression. RESULTS: We identified 12 clusters with different cognitive signatures that represent profiles of performance across multiple neuropsychological tests. These signatures significantly correlated with 26 variables including polygenic risk scores, physical and pulmonary functions, and blood biomarkers and were associated with the hazard of mortality (p < 0.01), cardiovascular disease (p = 0.03), dementia (p = 0.01), and skin cancer (p = 0.03). CONCLUSION: The identified cognitive signatures capture multiple domains simultaneously and provide a holistic vision of cognitive function, showing that different patterns of cognitive function can coexist in aging individuals. Such patterns can be used for clinical intervention and primary care.

EEG Reveals Alterations in Motor Imagery in People With Amnestic Mild Cognitive Impairment.

OBJECTIVES: Motor imagery has been used to investigate the cognitive mechanism of motor control. Although behavioral and electrophysiological changes in motor imagery in people with amnestic mild cognitive impairment (aMCI) have been reported, deficits in different types of imagery remain unclear. To explore this question, we used electroencephalography (EEG) to study neural correlates of visual imagery (VI) and kinesthetic imagery (KI) and their relationship to cognitive function in people with aMCI. METHODS: A hand laterality judgment task was used to induce implicit motor imagery in 29 people with aMCI and 40 healthy controls during EEG recording. Mass univariate and multivariate EEG analysis was applied to explore group differences in a data-driven manner. RESULTS: Modulation of stimuli orientation to event-related potential (ERP) amplitudes differed significantly between groups at 2 clusters located in the posterior-parietal and frontal areas. Multivariate decoding revealed sufficient representation of VI-related orientation features in both groups. Relative to healthy controls, the aMCI group lacked accurate representation of KI-related biomechanical features, suggesting deficits in automatic activation of KI strategy. Electrophysiological correlates were associated with episodic memory, visuospatial function, and executive function. Higher decoding accuracy of biomechanical features predicted better executive function via longer response time in the imagery task in the aMCI group. DISCUSSION: These findings reveal electrophysiological correlates related to motor imagery deficits in aMCI, including local ERP amplitudes and large-scale activity patterns. Alterations in EEG activity are related to cognitive function in multiple domains, including episodic memory, suggesting the potential of these EEG indices as biomarkers of cognitive impairment.

Self-perception and anticipated efficacy of the anti-dementia multimodal program in 100 older adults with mild cognitive impairment.

BACKGROUND: Effective and sustainable interventions are clearly needed for mild cognitive impairment (MCI) patients. Despite the clinical importance of the multimodal intervention approach, only one study using a multimodal approach demonstrated promising improvements in memory, attention, and executive functions, which also correlated with functional magnetic resonance imaging (MRI) blood oxygenation level dependent (BOLD) changes in cerebral activation in 50 MCI patients. OBJECTIVE: To investigate the self-perception and anticipated efficacy of each element of the BRAIN-FIT multimodal intervention program (robotic-assisted gait training (RAGT), computerized cognitive therapy, music, light, transcranial direct current stimulation (tDCS), and diaphragmatic breathing exercises) and the correlation between memory, concentration, depression, and sleep in older adults with MCI. METHODS: One hundred participants (mean±standard deviation: 8.63±78.4 years; 47 women) with MCI were recruited from a major university medical center and community dementia relief center. The survey questionnaire comprised four domains with 21 questions, including four pertaining to general demographic characteristics, eight related to exercise and activity, three related to sleep, and nine related to the BRAIN-FIT program. Chi-squared test was used to analyze the Likert scale data. The descriptive frequencies were calculated. Additionally, Spearman's rho statistics measure the rank-order association. The statistical significance was at P < 0.05. RESULTS: A strong correlation was observed between memory and concentration (r = 0.850, P = 0.000), memory and depression (r = 0.540, P = 0.000), memory and sleep (r = 0.502, P = 0.000), concentration and depression (r = 0.602, P = 0.000), concentration and sleep (r = 0.529, P = 0.000) and sleep and depression (r = 0.497, P = 0.000). The correlation between medical services and sleep (r = 0.249, P = 0.012) was moderate. The chi-square test revealed a significant difference in memory and low-intensity duration of exercise (χ2[3,N = 100] = 11.69, P = 0.01), concentration and high-intensity exercise duration (χ2[3,N = 100] = 10.08, P = 0.02), concentration with low-intensity exercise duration (χ2[3,N = 100] = 21.11, P = 0.00), depression with high-intensity (χ2[3,N = 100] = 10.36, P = 0.02), high-intensity duration of exercise (χ2[3,N = 100] = 10.48, P = 0.02); low-intensity (χ2[3,N = 100] = 7.90, P = 0.48), and low-intensity duration of exercise (χ2[3,N = 100] = 9.69, P = 0.02). Additionally, significant differences were observed between sleep and high-intensity (χ2[3, N = 100] = 10.36, P = 0.02), low-intensity (χ2[3, N = 100] = 18.14, P = 0.00), and low-intensity duration of exercise (χ2[3, N = 100] = 18.30, P = 0.00). Among the participants 5% answered RAGT, and 20% responded that they had experienced computerized cognitive therapy. Music therapy (20 %), diaphragmatic breathing exercises (45 %), and light therapy (10 %) were used. No patient had experienced tDCS. Conversely, 11% of the participants answered RAGT for programs they wanted to experience and 21% responded to computerized cognitive therapy. 25% of music therapy, 22% of diaphragmatic breathing exercises, 5% of light therapy, and 16% of tDCS participants said they wanted to experience it. Finally, 63% of the participants wanted to participate in the BRAIN-FIT program. CONCLUSION: The present study's results provide clinical evidence-based insights into the utilization of BRAIN-FIT in MCI to maximize cognitive score improvement of memory, concentration, depression, and sleep. Therefore, when designing the BRAIN-FIT, six intervention items were set in proportion to the preference based on the survey, to reduce participants' feeling of repulsion. The program was configured according to exercise intensity.

Musical and psychomotor interventions for cognitive, sensorimotor, and cerebral decline in patients with Mild Cognitive Impairment (COPE): a study protocol for a multicentric randomized controlled study.

BACKGROUND: Regular cognitive training can boost or maintain cognitive and brain functions known to decline with age. Most studies administered such cognitive training on a computer and in a lab setting. However, everyday life activities, like musical practice or physical exercise that are complex and variable, might be more successful at inducing transfer effects to different cognitive domains and maintaining motivation. "Body-mind exercises", like Tai Chi or psychomotor exercise, may also positively affect cognitive functioning in the elderly. We will compare the influence of active music practice and psychomotor training over 6 months in Mild Cognitive Impairment patients from university hospital memory clinics on cognitive and sensorimotor performance and brain plasticity. The acronym of the study is COPE (Countervail cOgnitive imPairmEnt), illustrating the aim of the study: learning to better "cope" with cognitive decline. METHODS: We aim to conduct a randomized controlled multicenter intervention study on 32 Mild Cognitive Impairment (MCI) patients (60-80 years), divided over 2 experimental groups: 1) Music practice; 2) Psychomotor treatment. Controls will consist of a passive test-retest group of 16 age, gender and education level matched healthy volunteers. The training regimens take place twice a week for 45 min over 6 months in small groups, provided by professionals, and patients should exercise daily at home. Data collection takes place at baseline (before the interventions), 3, and 6 months after training onset, on cognitive and sensorimotor capacities, subjective well-being, daily living activities, and via functional and structural neuroimaging. Considering the current constraints of the COVID-19 pandemic, recruitment and data collection takes place in 3 waves. DISCUSSION: We will investigate whether musical practice contrasted to psychomotor exercise in small groups can improve cognitive, sensorimotor and brain functioning in MCI patients, and therefore provoke specific benefits for their daily life functioning and well-being. TRIAL REGISTRATION: The full protocol was approved by the Commission cantonale d'éthique de la recherche sur l'être humain de Genève (CCER, no. 2020-00510) on 04.05.2020, and an amendment by the CCER and the Commission cantonale d'éthique de la recherche sur l'être humain de Vaud (CER-VD) on 03.08.2021. The protocol was registered at clinicaltrials.gov (20.09.2020, no. NCT04546451).

Tai Chi enhances cognitive training effects on delaying cognitive decline in mild cognitive impairment.

INTRODUCTION: Cognitive training and physical exercise have shown positive effects on delaying progression of mild cognitive impairment (MCI) to dementia. METHODS: We explored the enhancing effect from Tai Chi when it was provided with cognitive training for MCI. In the first 12 months, the cognitive training group (CT) had cognitive training, and the mixed group (MixT) had additional Tai Chi training. In the second 12 months, training was only provided for a subgroup of MixT. RESULTS: In the first 12 months, MixT and CT groups were benefited from training. Compared to the CT group, MixT had additional positive effects with reference to baseline. In addition, Compared to short-time training, prolonged mixed training further delayed decline in global cognition and memory. Functional magnetic resonance imaging showed more increased regional activity in both CT and MixT. DISCUSSION: Tai Chi enhanced cognitive training effects in MCI. Moreover, Tai Chi and cognitive mixed training showed effects on delaying cognitive decline.

Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial.

Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, Setting, and Participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. Main Outcomes and Measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Conclusions and Relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. Trial Registration: ClinicalTrials.gov Identifier: NCT02665481.

The Impact of a Yoga-Based Mindfulness Intervention versus Psycho-Educational Session for Older Adults with Mild Cognitive Impairment: The Protocol of a Randomized Controlled Trial.

BACKGROUND: There is a global agreement in the medical community that a significant proportion of dementia cases could be prevented or postponed. One of the factors behind this agreement comes from scientific evidence showing that mind-body interventions such as mindfulness and yoga for the elderly have been related to a range of positive outcomes, including improved cognition performance in seniors with mild cognitive impairment (MCI). OBJECTIVE: This study aims to evaluate the effectiveness of a yoga-based mindfulness intervention (YBM) versus psychoeducational sessions for older adults with MCI attending Hospital Clinic Universidad de Chile in Santiago. METHOD: Two-arm, individually randomized controlled trial (RCT) will be carried out at Clinical Hospital Universidad de Chile in Santiago. Older people over 60 years with any type of MCI using a score < 21 in the Montreal Cognitive Assessment (MoCA) test and a score of 0.05 in the Clinical Dementia Rating (CDR) Scale; and with preserved activities of daily living will be randomly assigned with an allocation ratio of 1:1 in either the yoga-based mindfulness intervention or the active control group based on the psycho-educational program. People who have performed yoga and/or mindfulness in the last 6 months or/and people with a psychiatric clinical diagnosis will be excluded from the study. Montreal Cognitive Assessment, the Lawton Instrumental Activities of Daily Living Scale (IADL), the Barthel Index (BI), the Pemberton happiness index, the Geriatric Anxiety Inventory (GAI) as well as the Geriatric Depression Scale (GDS-5) will be administered by blinded outcomes assessors before random assignment (Pre-test), the week following the last session of the intervention (post-test), and then after 3- and 6-months follow-up. RESULTS: The YBM intervention protocol based on a video recording has been adapted and designed. This is the first RCT to examine the effects of a yoga-based mindfulness intervention in improving cognitive and physical functions and mental health outcomes for Chilean elderly diagnosed with MCI. It is expected to be implemented as an acceptable and effective non-pharmacological option for older people with MCI. CONCLUSION: Providing evidence-based programs such as preventive therapy for Alzheimer's disease has relevant implications for public mental health services in Chile.

Associations of erythrocyte omega-3 fatty acids with cognition, brain imaging and biomarkers in the Alzheimer's disease neuroimaging initiative: cross-sectional and longitudinal retrospective analyses.

BACKGROUND: The association between omega-3 (ω-3) PUFAs and cognition, brain imaging and biomarkers is still not fully established. OBJECTIVES: The aim was to analyze the cross-sectional and retrospective longitudinal associations between erythrocyte ω-3 index and cognition, brain imaging, and biomarkers among older adults. METHODS: A total of 832 Alzheimer's Disease Neuroimaging Initiative 3 (ADNI-3) participants, with a mean (SD) age of 74.0 (7.9) y, 50.8% female, 55.9% cognitively normal, 32.7% with mild cognitive impairment, and 11.4% with Alzheimer disease (AD) were included. A low ω-3 index (%EPA + %DHA) was defined as the lowest quartile (≤3.70%). Cognitive tests [composite score, AD Assessment Scale Cognitive (ADAS-Cog), Wechsler Memory Scale (WMS), Trail Making Test, Category Fluency, Mini-Mental State Examination, Montreal Cognitive Assessment] and brain variables [hippocampal volume, white matter hyperintensities (WMHs), positron emission tomography (PET) amyloid-ß (Aß) and tau] were considered as outcomes in regression models. RESULTS: Low ω-3 index was not associated with cognition, hippocampal, and WMH volume or brain Aß and tau after adjustment for demographics, ApoEε4, cardiovascular disease, BMI, and total intracranial volume in the cross-sectional analysis. In the retrospective analysis, low ω-3 index was associated with greater Aß accumulation (adjusted ß = 0.02; 95% CI: 0.01, 0.03; P = 0.003). The composite cognitive score did not differ between groups; however, low ω-3 index was significantly associated with greater WMS-delayed recall cognitive decline (adjusted ß = -1.18; 95% CI: -2.16, -0.19; P = 0.019), but unexpectedly lower total ADAS-Cog cognitive decline. Low ω-3 index was cross-sectionally associated with lower WMS performance (adjusted ß = -1.81, SE = 0.73, P = 0.014) and higher tau accumulation among ApoE ε4 carriers. CONCLUSIONS: Longitudinally, low ω-3 index was associated with greater Aß accumulation and WMS cognitive decline but unexpectedly with lower total ADAS-Cog cognitive decline. Although no associations were cross-sectionally found in the whole population, low ω-3 index was associated with lower WMS cognition and higher tau accumulation among ApoE ε4 carriers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is registered at clinicaltrials.gov as NCT00106899.