High-frequency multimodal training with a focus on Tai Chi in people with Parkinson's disease: a pilot study.

Background and objectives: Cognitive decline is an important and common complication in patients with Parkinson's disease (PD) since it significantly reduces the quality of life. A breakthrough in treating and preventing cognitive decline in PD remains to be achieved. This study aimed to evaluate the effectiveness of high-frequency and intensive multimodal training in improving motor and cognitive function. Methods: Twenty-eight patients diagnosed with idiopathic PD completed a comprehensive neuropsychological test battery and were neurologically examined. The patients of the intervention group (n = 15) underwent 2 weekly sessions of Tai Chi therapy over 4 weeks and participated in an individually tailored training program consisting of two modules (smartphone-based speech training and cognitive training). A matched control group consisted of n = 13 patients with PD who received computer-assisted cognitive training. The data were analyzed with repeated-measures ANOVA. Results: Four weeks of high-frequency training showed significant effects on verbal and figural episodic memory and visuospatial function in the intervention group.Compared to the control group, the cognitive performance of the intervention group improved significantly in visuospatial function and figural episodic memory. A significant improvement was also shown in the intervention group in the Tinetti Mobility Test and the Epworth Sleepiness Scale. The significant effects in the Tinetti mobility test remained after the 6 months follow-up. After the intervention, the patients reported high motivation and satisfaction with the multimodal training. Conclusion: In patients with PD, a multimodal training program not only improves gait and stability but may also contribute to improving cognition. Clinical trial registration: ClinicalTrials.gov Identifier: NCT04103255; https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4.

Cognitive and Hippocampal Changes in Older Adults With Subjective Cognitive Decline After Acupuncture Intervention.

OBJECTIVE: Converging evidence indicates that subjective cognitive decline (SCD) could be an early indicator of dementia. The hippocampus is the earliest affected region during the progression of cognitive impairment. However, little is known about whether and how acupuncture change the hippocampal structure and function of SCD individuals. METHODS: Here, we used multi-modal MRI to reveal the mechanism of acupuncture in treating SCD. Seventy-two older participants were randomized into acupuncture or sham acupuncture group and treated for 12 weeks. RESULTS: At the end of the intervention, compared to sham acupuncture, participants with acupuncture treatment showed improvement in composite Z score from multi-domain neuropsychological tests, as well as increased hippocampal volume and functional connectivity. Moreover, the greater white matter integrity of the fornix, which is the major output tract of the hippocampus, was shown in the acupuncture group. CONCLUSION: These findings suggest that acupuncture may improve the cognitive function of SCD individuals, and increase hippocampal volume on the regional level and enhance the structural and functional connectivity of hippocampus on the connective level.

Cognitive protection and brain entropy changes from omega-3 polyunsaturated fatty acids supplement in late-life depression: A 52-week randomized controlled trial.

BACKGROUND: Late-life depression (LLD) is associated with risk of dementia, yet intervention of LLD provides an opportunity to attenuate subsequent cognitive decline. Omega-3 polyunsaturated fatty acids (PUFAs) supplement is a potential intervention due to their beneficial effect in depressive symptoms and cognitive function. To explore the underlying neural mechanism, we used resting-state functional MRI (rs-fMRI) before and after omega-3 PUFAs supplement in older adults with LLD. METHODS: A 52-week double-blind randomized controlled trial was conducted. We used multi-scale sample entropy to analyze rs-fMRI data. Comprehensive cognitive tests and inflammatory markers were collected to correlate with brain entropy changes. RESULTS: A total of 20 patients completed the trial with 11 under omega-3 PUFAs and nine under placebo. While no significant global cognitive improvement was observed, a marginal enhancement in processing speed was noted in the omega-3 PUFAs group. Importantly, participants receiving omega-3 PUFAs exhibited decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. The brain entropy changes of the PCG in the omega-3 PUFAs group correlated with improvement of language function and attenuation of interleukin-6 levels. LIMITATIONS: Sample size is small with only marginal clinical effect. CONCLUSION: These findings suggest that omega-3 PUFAs supplement may mitigate cognitive decline in LLD through anti-inflammatory mechanisms and modulation of brain entropy. Larger clinical trials are warranted to validate the potential therapeutic implications of omega-3 PUFAs for deterring cognitive decline in patients with late-life depression.

Underlying mechanisms behind the neuroprotective effect of vanillic acid against diabetes-associated cognitive decline: An in vivo study in a rat model.

Hippocampal synaptic dysfunction, oxidative stress, neuroinflammation, and neuronal loss play critical roles in the pathophysiology of diabetes-associated cognitive decline (DACD). The study aimed to investigate the effects of vanillic acid (VA), a phenolic compound, against DACD and explore the potential underlying mechanisms. Following confirmation of diabetes, rats were treated with VA (50 mg/kg/day; P.O.) or insulin (6 IU/rat/day; S.C.) for 8 consecutive weeks. The cognitive performance of the rats was evaluated using passive-avoidance and water-maze tasks. Long-term potentiation (LTP) was induced at hippocampal dentate gyrus (DG) synapses in response to high-frequency stimulation (HFS) applied to the perforant pathway (PP) to evaluate synaptic plasticity. Oxidative stress factors, inflammatory markers, and histological changes were evaluated in the rat hippocampus. This study showed that streptozotocin (STZ)-induced diabetes caused cognitive decline that was associated with inhibition of LTP induction, suppression of enzymatic antioxidant activities, enhanced lipid peroxidation, elevated levels of inflammatory proteins, and neuronal loss. Interestingly, chronic treatment with VA alleviated blood glucose levels, improved cognitive decline, ameliorated LTP impairment, modulated oxidative-antioxidative status, inhibited inflammatory response, and prevented neuronal loss in diabetic rats at a level comparable to insulin therapy. The results suggest that the antihyperglycemic, antioxidative, anti-inflammatory, and neuroplastic properties of VA may be the mechanisms behind its neuroprotective effect against DACD.

Therapeutic potential of curcumin on the cognitive decline in animal models of Alzheimer's disease: a systematic review and meta-analysis.

Curcumin, a polyphenol derived from the herb turmeric, has emerged as a prospective potential therapy in the treatment of Alzheimer's disease (AD). However, the efficacy of curcumin treatment in improving cognitive decline caused controversy recently. We aimed to systematically review the effect of curcumin on cognitive impairment in an animal model of AD. We conducted an exhaustive database search of related studies. Two investigators identified studies and independently extracted data. Stratified meta-analyses and meta-regression analyses were carried out to explore the sources of heterogeneity. Publication bias was assessed using funnel plots and Egger's test. Our systematic review included 33 articles. A meta-analysis of 29 publications showed that curcumin exerts significant positive effects on cognitive performance. For acquisition, the global estimated effect of curcumin was - 2.027 (95% CI - 2.435 to - 1.619, p < 0.001); for retention, the global estimated effect of curcumin was 1.606 (95% CI 1.101 to 2.111, p < 0.001). The stratified meta-analysis demonstrated that an increased effect size depended on diverse study characteristics. Additionally, publication bias was detected. We conclude that curcumin may reduce cognitive deficits in experimental AD. Furthermore, we emphasize that additional well-designed and well-reported animal studies are needed to inform further clinical studies.

The effectiveness of Kami Guibi-tang for cognitive impairment patients: A retrospective chart review.

Background: and Purpose: The number of patients with cognitive impairment is increasing worldwide. Therapeutic drugs that slow disease progression are being developed; however, further research is required. This study investigated the effects of Kami Guibi-tang on patients with various types of cognitive decline. Methods: This study was a single-center, retrospective chart review of patients who visited KyungHee University Hospital at Gangdong from January 2015 to March 2022. The study included participants who took Kami Guibi-tang for more than 90 days and were assessed on the Korean version Mini-Mental State Examination (MMSE-K) scores before and after treatment. Participants who received other liquid herbal medicines during the treatment were excluded. The outcome of interest was changed scores in MMSE-K and Short form of Geriatric Depression Scale (S-GDS). Results: A total of 31 participants were included. The total MMSE-K score significantly increased with time and showed a significant increase at 3 and 9 months compared with baseline. Among the MMSE-K subscores, the orientation subscore showed a significant increase at three months compared with baseline, and the attention and calculation subscore showed a significant increase with time. In addition, four participants with vascular dementia showed a significant increase in the total MMSE-K score over time and a significant increase after 9 months compared with baseline. The S-GDS score in 31 participants showed a significant decrease with time and at all time points compared with baseline. Conclusions: Kami Guibi-tang may improve cognitive function in patients with cognitive decline.

Nutritional strategies modulating the gut microbiome as a preventative and therapeutic approach in normal and pathological age-related cognitive decline: a systematic review of preclinical and clinical findings.

CONTEXT: The proportion of the elderly population is on the rise across the globe, and with it the prevalence of age-related neurodegenerative diseases. The gut microbiota, whose composition is highly regulated by dietary intake, has emerged as an exciting research field in neurology due to its pivotal role in modulating brain functions via the gut-brain axis. OBJECTIVES: We aimed at conducting a systematic review of preclinical and clinical studies investigating the effects of dietary interventions on cognitive ageing in conjunction with changes in gut microbiota composition and functionality. METHODS: PubMed and Scopus were searched using terms related to ageing, cognition, gut microbiota and dietary interventions. Studies were screened, selected based on previously determined inclusion and exclusion criteria, and evaluated for methodological quality using recommended risk of bias assessment tools. RESULTS: A total of 32 studies (18 preclinical and 14 clinical) were selected for inclusion. We found that most of the animal studies showed significant positive intervention effects on cognitive behavior, while outcomes on cognition, microbiome features, and health parameters in humans were less pronounced. The effectiveness of dietary interventions depended markedly on the age, gender, degree of cognitive decline and baseline microbiome composition of participants. CONCLUSION: To harness the full potential of microbiome-inspired nutrition for cognitive health, one of the main challenges remains to better understand the interplay between host, his microbiome, dietary exposures, whilst also taking into account environmental influences. Future research should aim toward making use of host-specific microbiome data to guide the development of personalized therapies.

Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and exposure to selenium species: A cross-sectional study.

Selenium is a trace element found in many chemical forms. Selenium and its species have nutritional and toxicologic properties, some of which may play a role in the etiology of neurological disease. We hypothesized that adherence to the Mediterranean-Dietary Approach to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet could influence intake and endogenous concentrations of selenium and selenium species, thus contributing to the beneficial effects of this dietary pattern. We carried out a cross-sectional study of 137 non-smoking blood donors (75 females and 62 males) from the Reggio Emilia province, Northern Italy. We assessed MIND diet adherence using a semiquantitative food frequency questionnaire. We assessed selenium exposure through dietary intake and measurement of urinary and serum concentrations, including speciation of selenium compound in serum. We fitted non-linear spline-based regression models to investigate the association between MIND diet adherence and selenium exposure concentrations. Adherence to the MIND diet was positively associated with dietary selenium intake and urinary selenium excretion, whereas it was inversely associated with serum concentrations of overall selenium and organic selenium, including serum selenoprotein P-bound selenium, the most abundant circulating chemical form of the metalloid. MIND diet adherence also showed an inverted U-shaped relation with inorganic selenium and particularly with its hexavalent form, selenate. Our results suggest that greater adherence to the MIND diet is non-linearly associated with lower circulating concentrations of selenium and of 2 potentially neurotoxic species of this element, selenoprotein P and selenate. This may explain why adherence to the MIND dietary pattern may reduce cognitive decline.

Potential mechanism of Qinggong Shoutao pill alleviating age-associated memory decline based on integration strategy.

CONTEXT: Qinggong Shoutao Wan (QGSTW) is a pill used as a traditional medicine to treat age-associated memory decline (AAMI). However, its potential mechanisms are unclear. OBJECTIVE: This study elucidates the possible mechanisms of QGSTW in treating AAMI. MATERIALS AND METHODS: Network pharmacology and molecular docking approaches were utilized to identify the potential pathway by which QGSTW alleviates AAMI. C57BL/6J mice were divided randomly into control, model, and QGSTW groups. A mouse model of AAMI was established by d-galactose, and the pathways that QGSTW acts on to ameliorate AAMI were determined by ELISA, immunofluorescence staining and Western blotting after treatment with d-gal (100 mg/kg) and QGSTW (20 mL/kg) for 12 weeks. RESULTS: Network pharmacology demonstrated that the targets of the active components were significantly enriched in the cAMP signaling pathway. AKT1, FOS, GRIN2B, and GRIN1 were the core target proteins. QGSTW treatment increased the discrimination index from -16.92 ± 7.06 to 23.88 ± 15.94% in the novel location test and from -19.54 ± 5.71 to 17.55 ± 6.73% in the novel object recognition test. ELISA showed that QGSTW could increase the levels of cAMP. Western blot analysis revealed that QGSTW could upregulate the expression of PKA, CREB, c-Fos, GluN1, GluA1, CaMKII-α, and SYN. Immunostaining revealed that the expression of SYN was decreased in the CA1 and DG. DISCUSSION AND CONCLUSIONS: This study not only provides new insights into the mechanism of QGSTW in the treatment of AAMI but also provides important information and new research ideas for the discovery of traditional Chinese medicine compounds that can treat AAMI.

Efficacy and safety of the integration of traditional Chinese medicine and western medicine in the treatment of diabetes-associated cognitive decline: a systematic review and meta-analysis.

Objective: In order to offer possible therapeutic treatment evidence for diabetes-associated cognitive decline (DACD), we thoroughly evaluated the effectiveness and safety of combining Traditional Chinese Medicine (TCM) and Western Medicine (WM) in the current study. Methods: The present study employed a comprehensive search strategy across multiple databases, namely, PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Scientific Journals Database (VIP), and Chinese Biomedical Literature Database (CBM), to identify relevant articles published until July 2023. Subsequently, a systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to assess the efficacy and safety of integrating TCM with WM for the treatment of DACD. The literature included in this study was assessed using the GRADE criteria and the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was conducted using RevMan 5.4 software. Results: A total of 20 RCTs involving 1,570 patients were ultimately included in this meta-analysis. The pooled results demonstrated that the integration of TCM and WM therapy significantly enhanced the overall effectiveness rate compared to WM therapy alone [OR = 4.94, 95% CI (3.56, 6.85), p < 0.00001]. Additionally, the combination therapy resulted in reductions in fasting blood glucose [MD = -0.30, 95% CI (-0.49, -0.10), p = 0.003], HbA1c [MD = -0.71, 95%CI (-1.03, -0.40), p < 0.00001], TNF-α levels [MD = -8.28, 95%CI (-13.12, -3.44), p = 0.0008], and TCM Syndrome Score [MD = -5.97, 95%CI (-9.06, -2.88), p = 0.0002]. Meanwhile, the combination therapy had a positive effect on MoCA Score [MD = 2.52, 95% CI (1.75, 3.30), p < 0.00001], and MMSE Score [MD = 2.31, 95% CI (1.33, 3.29), p < 0.00001]. In addition, the safety of the combination therapy was comparable to that of the WM alone [OR = 0.40, 95% CI (0.12, 1.31), p = 0.13]. Conclusion: The integration of TCM and WM therapy outperformed WM alone in DACD treatment. Simultaneously, the combination therapy could improve the therapeutic effect on blood glucose, cognitive function, and inflammation to a certain extent with few adverse effects. However, given the constraints imposed by the quality limitations of the incorporated studies, as well as the potential presence of reporting bias, it is imperative that our findings be substantiated through rigorous, large-scale, randomized controlled trials of superior quality in the future.

Effect of acupuncture at neck-Jiaji (EX-B 2) and tuina on the cognitive function in the patients with subjective cognitive decline. / é’ˆåˆºé¢ˆå¤¹è„Šç©´è”åˆæŽ¨æ‹¿å¯¹ä¸»è§‚è®¤çŸ¥ä¸‹é™æ‚£è€ è®¤çŸ¥åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the effects on cognitive function, sleep quality and hemodynamics in the patients with subjective cognitive decline (SCD) after treated with acupuncture at neck-Jiaji (EX-B 2) and tuina on the base of healthy lifestyle education and meta-memory training. METHODS: Sixty SCD patients were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 3 cases dropped out). In the control group, the healthy lifestyle education and meta-memory training was performed, twice daily, 15 min each time; the 5-day intervention was delivered a week, lasting consecutively 4 weeks. On the base of the intervention as the control group, in the observation group, acupuncture at neck-Jiaji (EX-B 2) and tuina was conducted. First, one-finger pushing and plucking method of tuina was exerted on the neck region along the running courses of the bladder meridian of foot-taiyang and the governor vessel, for 10 min to 15 min; afterwards, acupuncture was delivered at bilateral neck-Jiaji (EX-B 2), from C1 to C7; and the needles were retained for 30 min. This intervention was given once daily, 5 times a week, for consecutive 4 weeks. Before and after treatment, the score of the mini-mental state examination (MMSE), the score of full scale memory quotient (FSMQ) were assessed by Wechsler memory scale-fourth edition (WMS-Ⅳ) and the score of the Pittsburgh sleep quality index (PSQI) was compared between the two groups. Using transcranial Doppler ultrasound, the hemodynamic indexes (the mean velocity [Vm] and pulsatility index [PI] of the left vertebral artery [LVA], the right vertebral artery [RVA] and the basilar artery [BA]) were determined in the two groups. RESULTS: After treatment, the scores of MMSE and FSMQ increased compared with those before treatment in the two groups (P<0.05, P<0.001), PSQI score was lower (P<0.05) and Vm of BA was higher (P<0.001) in the observation group when compared with those before treatment. The scores of MMSE and FSMQ, as well as Vm of BA were higher (P<0.05, P<0.001), and PSQI score was decreased (P<0.05) in the observation group when compared with the control group. CONCLUSIONS: The combined therapy of acupuncture at neck-Jiaji (EX-B 2) and tuina is more advantageous to improving cognitive function, relieving chronic emotional stress and ameliorating sleeping quality in the patients with subjective cognitive decline, which may be achieved by improving the blood supply of the basilar artery.

Promoting hearing and cognitive health in audiologic rehabilitation for the well-being of older adults.

OBJECTIVE: With our aging population, an increasing number of older adults with hearing loss have cognitive decline. Hearing care practitioners have an important role in supporting healthy aging and should be knowledgeable about cognitive decline and associated management strategies to maximize successful hearing intervention. METHODS: A review of current research and expert opinion. RESULTS: This article outlines the association between hearing loss and cognitive decline/dementia, hypothesized mechanisms underlying this, and considers current research into the effects of hearing intervention on cognitive decline. Cognition into old age, cognitive impairment, dementia, and how to recognize cognitive decline that is not part of normal aging are described. Screening of older asymptomatic adults for cognitive decline and practical suggestions for the delivery of person-centered hearing care are discussed. Holistic management goals, personhood, and person-centered care in hearing care management are considered for older adults with normal cognitive aging through to dementia. A case study illustrates important skills and potential management methods. Prevention strategies for managing hearing and cognitive health and function through to older age, and strategies to maximize successful hearing aid use are provided. CONCLUSION: This article provides evidence-based recommendations for hearing care professionals supporting older clients to maximize well-being through the cognitive trajectory.

Exploring the Interrelationships between Diabetes, Nutrition, Anxiety, and Depression: Implications for Treatment and Prevention Strategies.

Across the world, diabetes, depression, and anxiety symptoms have gained widespread recognition as significant public health issues. Recent research has unveiled a mutually influential relationship between diabetes and these two mental health conditions, where each disorder impacts the course and outcomes of the others. The role of nutrition emerges as pivotal in preventing and treating depression, anxiety, and diabetes. A thorough literature review was undertaken to investigate the reciprocal effects between anxiety, depression, and diabetes, including their impact on the development and severity of each condition. Additionally, the effects of nutrition on the prevention and management of depression, anxiety, diabetes, and related complications in at-risk individuals were assessed. Our findings show that mental disorders, such as depression and anxiety, increase the risk of developing type 2 diabetes and are associated with poorer glycemic control, increased diabetes-related complications, and higher mortality rates. Conversely, diabetes is also linked with an increased risk of developing depression and anxiety. The biological, psychological, and social factors that contribute to the comorbidity between these two conditions are complex and multifaceted. Therefore, an integrated approach to the management of both conditions is critical for improving patient outcomes and reducing the overall burden of disease. Nutritional interventions should be utilized to reduce the risk of diabetes in patients with anxiety and depression as well as enhance mental health in patients with diabetes.

Effect of Kami Guibi-tang (KGT) in elderly subjects with insomnia: a study protocol from a single center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The incidence of insomnia increases with age and is related to cognitive function in older adults; therefore, it is important to manage it actively. In this study, we report a protocol for the evaluation of the efficacy and safety of Kami Guibi-tang (KGT), a herbal prescription that has been widely used in East Asia for insomnia, forgetfulness, and depression, in older adults with insomnia. METHODS: In this single-center, double-blind, randomized controlled trial, 60 older adults with insomnia and subjective cognitive decline will be recruited and randomly assigned to the KGT or placebo group. The KGT group will take KGT granules thrice a day for 12 weeks, whereas the control group will take placebo granules in the same manner. Participants will be assessed for sleep, cognitive function, quality of life, and depression using the Pittsburgh Sleep Quality Index-Korean (PSQI-K), Insomnia Severity Index-Korean (ISI-K), Seoul Neuropsychological Screening Battery-Dement (SNSB-D), 36-item MOS Short Form Survey (SF-36) and Short version of the Geriatric Depression Scale (S-GDS) before and at the end of administration of the investigational product. The PSQI-K, ISI-K, and SF-36 will be further assessed 12 weeks after the end of medication to determine whether the effects on sleep and quality of life are sustained. The PSQI-K total score difference between the two groups at 12 and 24 weeks will be the primary outcome; all other endpoints will be secondary. Safety will be assessed by performing blood tests and electrocardiograms before taking the investigational drug, 6 weeks after taking the drug, and 12 weeks after taking the drug; any adverse events will be observed throughout the study. DISCUSSION: The protocol will provide a detailed process for a clinical trial to evaluate the efficacy and safety of KGT in elderly patients with insomnia. We will also investigate if changes in cognitive function correlated with improvements in insomnia. TRIAL REGISTRATION: This trial was registered at CRIS (Clinical Research Information Service) on April 27, 2023 (KCT0008391, version 2.0).  https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24811&search_page=L .

Occupational Therapist-Led Mindfulness Training Program for Older Adults Living with Early Cognitive Decline in Primary Care: A Pilot Randomized Controlled Trial.

Background: Community-dwelling older adults with early cognitive deficits experience less efficiency in performing everyday life tasks, resulting in decreased satisfaction and other adverse psychological outcomes. Mindfulness training has been linked to cognitive and psychological improvements and, most recently, has been identified as a potential intervention supporting performance of everyday life activities. Objective: This study aimed to evaluate whether mindfulness practice can improve perceived performance and satisfaction with everyday life activity and secondary psychological outcomes. Methods: This study is a pilot randomized controlled trial (RCT) in an interprofessional primary care team practice in Toronto, Ontario, Canada. The participants were 27 older adults aged 60 years of age or older living with early cognitive deficits. Participants were randomized into an 8-Week mindfulness training program (n = 14) group or a Wait-List Control (WLC; n = 13) group compared at baseline, post-intervention and 4-weeks follow-up. MANOVAs with post-hoc independent t-tests were used to compare between groups at different time points. Results: There was a significant improvement in anxiety for the intervention group compared to the WLC group at post-intervention; Time-2 (mean difference = 3.90; CI = 0.04-7.75; p = 0.04) with large effect size (d = 0.80). Conclusion: Mindfulness training significantly improved anxiety scores for patients with early cognitive deficits post-intervention. Further work is required to test the sustainability of reduced anxiety over time, but this study demonstrated that MBSR is a promising primary care intervention for those living with early cognitive deficits. This study warrants the pursuit of a future study in exploring how long the reduced anxiety effects would be sustained.

Addressing the Chronic Pain-Early Cognitive Decline Comorbidity Among Older Adults: Protocol for the Active Brains Remote Efficacy Trial.

BACKGROUND: Chronic pain and early cognitive decline, which are costly to treat and highly prevalent among older adults, commonly co-occur, exacerbate one another over time, and can accelerate the development and progression of Alzheimer disease and related dementias. We developed the first mind-body activity program (Active Brains [AB]) tailored to the needs of older adults with chronic pain and early cognitive decline. Results from our previous study strongly supported the feasibility of conducting AB remotely and provided evidence for improvements in outcomes. OBJECTIVE: We are conducting a single-blinded, National Institutes of Health stage-2, randomized clinical trial to establish the efficacy of AB versus a time-matched and dose-matched education control (Health Enhancement Program [HEP]) in improving self-reported and objective outcomes of physical, cognitive, and emotional functions in 260 participants. The methodology described in this paper was informed by the lessons learned from the first year of the trial. METHODS: Participants are identified and recruited through multidisciplinary clinician-referred individuals (eg, pain psychologists and geriatricians), the Rally Research platform, social media, and community partnerships. Interested participants complete eligibility screening and electronic informed consent. Baseline assessments include self-report, performance-based measures (eg, 6-min walk test) and objective measures (eg, Repeatable Battery for the Assessment of Neuropsychological Status). Participants are mailed a wrist-worn ActiGraph device (ActiGraph LLC) to passively monitor objective function (eg, steps) during the week between the baseline assessment and the beginning of the programs, which they continue to wear throughout the programs. After baseline assessments, participants are randomized to either AB or HEP and complete 8 weekly, remote, group sessions with a Massachusetts General Hospital psychologist. The AB group receives a Fitbit (Fitbit Inc) to help reinforce increased activity. Assessments are repeated after the intervention and at the 6-month follow-up. Coprimary outcomes include multimodal physical function (self-report, performance based, and objective). Secondary outcomes are cognitive function (self-report and objective), emotional function, and pain. RESULTS: We began recruitment in July 2022 and recruited 37 participants across 4 cohorts. Of them, all (n=37, 100%) have completed the baseline assessment, 26 (70%) have completed the posttest assessment, and 9 (24%) are actively enrolled in the intervention (total dropout: n=2, 5%). In the three cohorts (26/37, 70%) that have completed the AB or HEP, 26 (100%) participants completed all 8 group sessions (including minimal makeups), and watch adherence (1937/2072, 93.48%, average across ActiGraph and Fitbit devices) has been excellent. The fourth cohort is ongoing (9/37, 24%), and we plan to complete enrollment by March 2026. CONCLUSIONS: We aim to establish the efficacy of the AB program over a time-matched and dose-matched control in a live video-based trial and test the mechanisms through theoretically driven mediators and moderators. Findings will inform the development of a future multisite effectiveness-implementation trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05373745; https://classic.clinicaltrials.gov/ct2/show/NCT05373745. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47319.

Structured Docosahexaenoic Acid (DHA) Enhances Motility and Promotes the Antioxidant Capacity of Aged C. elegans.

The human lifespan has increased over the past century; however, healthspans have not kept up with this trend, especially cognitive health. Among nutrients for brain function maintenance, long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFA): DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) must be highlighted, particularly structured forms of EPA and DHA which were developed to improve bioavailability and bioactivity in comparison with conventional ω-3 supplements. This study aims to elucidate the effect of a structured triglyceride form of DHA (DHA-TG) on the healthspan of aged C. elegans. Using a thrashing assay, the nematodes were monitored at 4, 8, and 12 days of adulthood, and DHA-TG improved its motility at every age without affecting lifespan. In addition, the treatment promoted antioxidant capacity by enhancing the activity and expression of SOD (superoxide dismutase) in the nematodes. Lastly, as the effect of DHA-TG was lost in the DAF-16 mutant strain, it might be hypothesized that the effects of DHA need DAF-16/FOXO as an intermediary. In brief, DHA-TG exerted a healthspan-promoting effect resulting in both enhanced physical fitness and increased antioxidant defense in aged C. elegans. For the first time, an improvement in locomotive function in aged wild-type nematodes is described following DHA-TG treatment.

Effects of mindfulness-based interventions on neuropsychiatric symptoms and psychological well-being on people with subjective cognitive decline and mild cognitive impairment: A meta-analysis.

OBJECTIVES: Neuropsychiatric symptoms (NPS) are highly prevalent in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI), and are strongly linked to accelerated cognitive decline and dementia onset. While mindfulness-based interventions have shown promise in improving psychological well-being in clinical and community settings, their efficacy for individuals in these pre-dementia stages remains unclear. This meta-analysis examined the effects of mindfulness-based interventions on NPS and psychological outcomes in these preclinical cohorts. METHODS: Eligible studies were retrieved from PubMed, EMBASE, JBI EPB, Web of Science, and Cochrane library. Two independent researchers conducted the literature search and data extraction. Cochrane Risk-of-Bias Assessment Tool was used to assess the methodological quality of included studies. Quality of evidence was evaluated using the GRADE approach. Intervention effects were estimated by Hedge's g and 95% confidence interval (CI). RESULTS: A total of 18 randomized controlled trials (including 974 participants from 21 studies) were included in the meta-analysis. The results demonstrated statistically significant immediate post-intervention effects of mindfulness-based interventions on anxiety (g = -0.30, 95% CI -0.49 to -0.11), stress (g = -0.58, 95% CI -0.91 to -0.24), and quality of life (g = 0.50, 95% CI 0.12-0.87). However, no significant effects were found for depression, apathy, mindfulness, and stress-related biomarkers. Follow-up data analysis also did not reveal significant effects for depression and anxiety. CONCLUSIONS: The findings of this meta-analysis suggest that mindfulness-based interventions may improve anxiety, stress, and quality of life in individuals with SCD and MCI. However, more rigorous randomized controlled trials with larger sample sizes and evaluation using physiological parameters are needed to establish more definitive conclusions. Future interventions could consider incorporating cognitive training and health education to address the specific needs of the pre-dementia population. REGISTRATION NUMBER: PROSPERO: CRD42022359906.

Aging and Oral Health: Biological and Sociobehavioral Perspectives.

As the life expectancy and growth of the aging population increase globally, efforts to promote healthy longevity become more important. Holistic policy guidelines and actions have been designed to advocate and fortify healthy aging at multiple levels. Oral health, a fundamental contributor of overall health and well-being, forms a core part of the noncommunicable disease agenda within the sustainable development goals set by the World Health Organization. Aging significantly heightens the risk of myriad oral disorders and other noncommunicable diseases. As of 2019, oral disorders accounted for 8.9 million disability-adjusted life-years in individuals older than 60 y. In addition to the development of multidisciplinary aging-friendly policies to promote healthy aging, basic biology and translational research has been encouraged that focuses on deciphering the underlying mechanisms involved in age-related physical and cognitive decline or dysregulation of oral tissues. Given the relevance of oral health aging as a critical component of the One Health Initiative, this special issue encompasses a collection of articles dedicated to recent advances in the behavioral and social implications of age-related oral diseases and tooth loss on several aspects of the quality of life of adults as they age. Furthermore, it includes articles detailing molecular mechanisms associated with cellular aging and their implications for oral tissue health, periodontal disease severity, and the regenerative potential of stem cells.

Effect of a 1-Year Nutritional Blend Supplementation on Plasma p-tau181 and GFAP Levels among Community-Dwelling Older Adults: A Secondary Analysis of the Nolan Trial.

Background: Observational studies and some randomized controlled trials have suggested that nutritional supplementation could be a possible intervention pathway to prevent cognitive decline and Alzheimer's disease (AD). As measuring amyloid-ß and tau pathophysiology by positron emission tomography (PET) or cerebrospinal fluid (CSF) analyses may be perceived as complex, plasma versions of such biomarkers have emerged as more accessible alternatives with comparable capacity of predicting cognitive impairment. Objectives: This study aimed to evaluate the effect of a 1-year intervention with a nutritional blend on plasma p-tau181 and glial fibrillary acidic protein (GFAP) levels in community-dwelling older adults. Effects were further assessed in exploratory analyses within sub-cohorts stratified according to p-tau status (with the third tertile considered as high: ≥15.1 pg/ mL) and to apolipoprotein E (APOE) ε4 allele status. Methods: A total of 289 participants ≥70 years (56.4% female, mean age 78.1 years, SD=4.7) of the randomized, double-blind, multicenter, placebo-controlled Nolan trial had their plasma p-tau181 assessed, and daily took either a nutritional blend (composed of thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, cobalamin, vitamin E, vitamin C, vitamin D, choline, selenium, citrulline, eicosapentaenoic acid - EPA, and docosahexaenoic acid - DHA) or placebo for 1 year. Results: After 1-year, both groups presented a significant increase in plasma p-tau181 and GFAP values, with no effect of the intervention (p-tau181 between-group difference: 0.27pg/mL, 95%CI: -0.95, 1.48; p=0.665; GFAP between-group difference: -3.28 pg/mL, 95%CI: -17.25, 10.69; p=0.644). P-tau-and APOE ε4-stratified analyses provided similar findings. Conclusions: In community-dwelling older adults, we observed an increase in plasma p-tau181 and GFAP levels that was not different between the supplementation groups after one year.