Explore the vast range of titles available.

Background Physical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy. Methods The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 × 10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels. Discussion The SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance and mobility outcomes in MCI. These interventions may contribute to new approaches to stabilize and reverse cognitive-mobility decline in older individuals with MCI. Trial Registration Identifier: NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676 .

Objectives Objective 1: To determine if it is feasible to conduct an RCT of online Sudarshan Kriya Yoga (SKY) for frontline hospital and long-term care home staff under the constraints imposed by the COVID-19 pandemic and need for remote trial monitoring. Objective 2: To assess whether online versions of SKY and/or Health Enhancement Program (HEP) result in improvement in self-rated measures of insomnia, anxiety, depression, and resilience. Trial design This is an open-label feasibility randomized controlled trial (RCT), comparing an online breath based yogic intervention SKY versus an online control mind-body intervention HEP in frontline hospital and long-term care home staff managing the COVID-19 pandemic. Participants Participants will include frontline hospital and long-term care home staff that are involved in the management of COVID-19 patients in London, Ontario, Canada. Participants will be willing and able to attend via online video conferencing software to participate in the study interventions. Participants must have an adequate understanding of English and be able to sit without physical discomfort for 60 minutes. Intervention and comparator Sudarshan Kriya Yoga (SKY) : The online version of SKY will be delivered by at least one certified Canadian SKY teacher, with at least one back up teacher at all times, under the supervision of Ms. Ronnie Newman, Director of Research and Health Promotion, Art of Living Foundation, USA. The online version of SKY for healthcare workers has a total duration of 3 hours. Phase I will consist of 5 self-paced online modules of 4-10 minutes each to learn the breath control techniques. Participants will be sent an online survey in REDCap requesting that they self-confirm completion of the Phase I modules. In Phase II, 2 interactive online sessions of 1 hour each will be held on consecutive days with a certified SKY teacher, during which participants will learn the fast, medium and slow breaths. For ease of scheduling, multiple time windows will be offered for Phase II. There will be at least one back up teacher at all times. Both Phase I and II will be completed in the first week. Health Enhancement Program (HEP) : The active control arm, HEP, will consist of time-matched online self-paced modules for Phase I. Phase II will consist of mindfulness-based meditation sessions delivered by mental health staff. HEP will be an active treatment program that incorporates mind-body interventions. HEP will consist of time-matched online self-paced modules with psychoeducation on healthy active living as well as interactive modules comprising of guided de-stressing exercises including music therapy, mindfulness and progressive muscle relaxation. Weekly follow up sessions will be offered to all recruited participants for 30 minutes each for the subsequent 4 weeks in both study arms. Main outcomes The following feasibility outcomes will be measured at the end of the study: (1) rate of participant recruitment, (2) rate of retention, (3) completeness of data entry, (4) cost of interventions, and (5) unexpected costs. Such measures will be collected on a daily basis through-out the study and tabulated 5 weeks later at the end of the study. Randomisation Participants will be randomized after they have electronically signed the consent form and the research staff have confirmed eligibility. We will use REDCap to perform randomization in a 1:1 ratio as well as allocation concealment. REDCap is widely used by health researchers worldwide to significantly reduce data entry and study management errors to improve data fidelity. Blinding (masking) All study participants will be blinded to the study hypotheses so as to prevent any expectation bias. Group allocation will be masked during analysis. Numbers to be randomised (sample size) This study will randomize a total of 60 participants in a 1:1 ratio to either SKY or HEP interventions. Trial Status Protocol version number 2.0 (June 5, 2020). Recruitment is currently ongoing (starting June 25, 2020). We anticipate to complete recruitment by June 30, 2021 and complete the study by September 30, 2021. Trial registration ClinicalTrials.gov protocol ID NCT04368676 (posted April 30, 2020). Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Bipolar disorder prevalence rates vary in the older adult population (defined as age ≥ 65 years), ranging from 1% in community dwellers to as high as 8–10% in hospital inpatients. Although older agents, including lithium and valproic acid, offer significant antimanic efficacy, as supported by a recent randomized controlled trial (RCT), there is growing interest in using atypical antipsychotics to treat bipolar disorder in older adults. Newer atypical antipsychotics are of interest based on their tolerability and efficacy in the general adult bipolar population. The aim of this review was to systematically examine efficacy and tolerability of newer atypical antipsychotics for older adult bipolar disorder (OABD). We conducted a systematic search utilizing the MEDLINE, EMBASE, PsycINFO and Cochrane Library electronic databases, with the aim of identifying all RCTs comparing newer atypical antipsychotics approved by the US FDA since 2002 (including brexpiprazole, cariprazine, lurasidone, iloperidone, asenapine, paliperidone, and aripiprazole) with placebo or another comparator, in the treatment of any phase of bipolar disorder (including mania, depression or mixed episodes while used as an acute or maintenance treatment) in older adults (> 65 years). We found no RCT data on any of the examined agents. Hence, we changed our search criteria to include studies with a lower age cut-off (≥ 55 years), as well as the inclusion of post hoc studies. Two post hoc studies on lurasidone suggest its reasonable safety and efficacy profile in the acute and maintenance treatment of OABD; however, there are no pharmacoeconomic data on the use of lurasidone in the treatment of OABD. Research data from open-label studies on oral asenapine and aripiprazole as add-on therapy suggest that these two agents are adequately tolerated and improved symptoms of depression and mania in OABD; hence, there is an urgent need to conduct RCTs on these two agents. Lastly, we found no studies for the treatment of OABD with brexpiprazole, cariprazine, iloperidone, or paliperidone.

The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. (“GUIDED”), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian “GAPP-MDD” RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477).

Structural brain abnormalities are associated with late-life major depression, with numerous studies reporting increased white matter hyperintensities (WMH) and reduced cortical/subcortical grey matter volumes. There is strong evidence linking vascular disease to WMH, but limited evidence on its association with subcortical volumes. To investigate the relationship of orthostatic blood pressure changes to WMH and subcortical grey matter volumes in late-life depression. Thirty-eight people with depression and a similarly aged comparison group (n = 30) underwent fluid attenuated inversion recovery (FLAIR) and T(1)-weighted magnetic resonance imaging as well as systematic orthostatic blood pressure assessments. Volumetric estimates of WMH and subcortical grey matter were obtained for each participant and the relationship to blood pressure drop on active stand was examined. An association between orthostatic systolic blood pressure drop and WMH volumes in temporal and parietal regions was found in the depression group (age-corrected partial correlation r' = 0.31-0.35, P<0.05). Subcortical volumes were not related to blood pressure changes or WMH volumes in either group. We found evidence for an association between the degree of orthostatic systolic blood pressure drop and WMH volume in the depression group. Since blood pressure drops lead to WMH in animals our findings suggest systolic blood pressure drops may be a factor contributing to these lesions in late-life depression.

The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia.

To explore the relationship between specific aspects of cognition, white matter hyperintensities (WMHs), and cardiovascular autonomic parameters in late-life depression (LLD). Cross-sectional analysis. Secondary care psychiatry. Forty-one individuals older than 60 years, with current or previous history of major depression, and 32 age-matched comparison subjects. Cognition was assessed by a standardized computer battery of tasks (Cognitive Drug Research) that measured processing speed, attention, episodic memory, and working memory. Cardiovascular autonomic parameters were estimated by a noninvasive device that calculated blood pressure, heart rate variability, and baroreflex sensitivity (Task Force Monitor). Magnetic resonance imaging was performed on a 3-T magnetic resonance imaging system, and WMH volume was estimated using an automated validated method. As expected, cognitive deficits in all tested domains were present in LLD subjects compared with comparison subjects. In the LLD group, processing speed was correlated with scores on memory and working memory tasks. Attentional deficits were correlated with total and periventricular WMH volume, and episodic memory was associated with heart rate variability. There were no associations between cognitive variables and traditional vascular risk factors or between cognitive variables and any of these parameters in the comparison subjects. This study suggests that processing speed may be an important factor underlying deficits in LLD, but it also indicates that other factors, including those related to vascular disease, are important and thus provide further support for the vascular depression hypothesis.

A limited number of studies have demonstrated changes in cerebral blood flow (CBF) in older individuals with depression, but there are considerable inconsistencies between studies. To investigate changes in CBF using arterial spin labelling (ASL) magnetic resonance imaging (MRI) in people with late-life depression and in a similarly aged healthy control group. Sixty-eight participants (30 healthy individuals, 38 with depression) underwent ASL and T(1)-weighted MRI scanning. For each individual, regional estimates of separate grey and white matter CBF were obtained. Group differences in CBF and their associations with clinical features were examined. Significant increases were observed in white matter CBF in patients with depression relative to the control group (F(1,65) = 9.7, P = 0.003). Grey matter CBF in lateral frontal, medial frontal, cingulate, central and parietal regions did not significantly differ between groups (F(1,65)≤2.1, P≥0.2). A significant correlation was found between white matter CBF and Montgomery-Åsberg Depression Rating Scale (MADRS) scores in depression (r' = -0.42, P = 0.03). Further analyses revealed that compared with controls, significant elevation of white matter CBF was apparent in participants whose depression was in remission (n = 21, MADRS≤10, P = 0.001) but not in those with current depression (n = 17, MADRS≥11, P = 0.80). Findings suggest a compensatory response to white matter pathological change or a response to (or a predictor of) successful antidepressant treatment, perhaps by facilitating neurotransmission in specific circuits and so reducing depressive symptoms.

Background Various service provision models for youth at risk of homelessness have been researched and implemented, including access to housing and physical and mental health resources. However, even with these interventions, we remain unaware of how best to manage symptoms of depression and anxiety and the rate of drug use in these populations primarily because of a lack of feasibility data. Methods This paper presents the results of a mixed-methods study in London, Canada, that examined the feasibility of implementing a biopsychosocial intervention, SKY Schools, in at-risk youth aged between 16 and 25 ( n  = 49). The study also recorded qualitative responses about the program’s usefulness from the perspective of the service users. The SKY Schools intervention consisted of social-emotional learning combined with Sudarshan Kriya Yoga, a standardized yoga-based breathing exercise routine. The intervention program was divided into two phases: an active learning phase and a reinforcement phase. The following feasibility outcome measures were collected: (1) the number of potential participants approached per month, (2) number (proportion) who were successfully screened, (3) the proportion of screened participants who enrolled, (4) the rate of retention in the study, (5) rate of adherence to study protocol, (6) proportion of planned ratings that were completed, (7) intervention cost per case, (8) completeness of final data for analysis, (9) length of time to collect all data, (10) quality of all collected data, (11) determining if partnering community organizations were willing to conduct the study as per study protocol, (12) determining if there were any capacity issues with partners providing intervention and investigators being able to perform the tasks that they were committed to doing, (13) determining if there were any problems of entering the data into a computer, (14) preliminary data about the safety of the intervention, and (15) preliminary estimate of treatment effects. Results All feasibility outcome measures were collectible. In the city of London, Canada it was feasible to conduct a pilot study in this population of youth at risk of homelessness. Foremost among the findings was a high retention rate (61.2%) and overall positive qualitative feedback with a number of potential suggestions to improve the delivery and quality of the intervention. However, we had a significantly low recruitment rate (0.27 participants per week) suggesting that multiple sites will be needed to achieve an adequate sample size for a subsequent definitive trial. Conclusions Future researchers may consider the findings of this feasibility study when designing a randomized control trial to further assess the efficacy and tolerability of SKY Schools. Trial registration Trial registration: Clinicaltrials.gov, identifier NCT02749240. Registered April 22, 2016, https://clinicaltrials.gov/ct2/show/NCT02749240 .

Background Recent estimates suggest an 11% prevalence of current late-life depression (LLD) and a lifetime prevalence of 16–20%. LLD leads to cognitive disturbance as well as a nearly two to three times increased risk of dementia. We conducted a recent randomized controlled trial (RCT) which demonstrated that Sahaj Samadhi meditation (SSM), an easy-to-implement, meditation-based augmentation strategy, led to higher rates of symptom remission when compared to treatment as usual (40.0 vs 16.3%; odds ratio, 3.36; 95% CI 1.06–10.64; p  = 0.040). Here we present a protocol describing a two-site, blinded, RCT, comparing an SSM arm to an active-control arm – a Health Enhancement Program (HEP) intervention – in their ability to reduce depressive symptoms and improve executive functioning, among several other exploratory outcomes. Methods/design One hundred and ninety-two ( n  = 192) participants with LLD will be recruited at two sites (London, ON, Canada, and Montreal, QC, Canada). Participants will undergo stratified randomization with regards to site and the presence of treatment-resistant-LLD (TR-LLD) or not, to either SSM or HEP. We will assess change in (1) depression severity using the Hamilton Depression Rating Scale (HAM-D), (2) executive functioning, and (3) other exploratory physiological and mood-based measures, at baseline (0 weeks), post intervention (12 weeks), and 26 weeks after baseline. Raters, clinicians, and care providers will be blinded to group allocation while participants will be blinded to the study hypotheses. Discussion This study should more definitively assess whether SSM can be used as an augmentation strategy in routine clinical care for patients suffering from LLD and TR-LLD. If the effects of SSM are significantly better than HEP, it will offer support for the routine use of this intervention to manage LLD/TR-LLD and comorbid declines in executive dysfunction. The results of this study could also inform whether SSM can improve/prevent cognitive decline in LLD. Trial registration ClinicalTrials.gov, ID: NCT03564041 . Registered on 20 June 2018.