CDK12 is hyperactivated and a synthetic-lethal target in BRAF-mutated melanoma.

Melanoma is the deadliest form of skin cancer and considered intrinsically resistant to chemotherapy. Nearly all melanomas harbor mutations that activate the RAS/mitogen-activated protein kinase (MAPK) pathway, which contributes to drug resistance via poorly described mechanisms. Herein we show that the RAS/MAPK pathway regulates the activity of cyclin-dependent kinase 12 (CDK12), which is a transcriptional CDK required for genomic stability. We find that melanoma cells harbor constitutively high CDK12 activity, and that its inhibition decreases the expression of long genes containing multiple exons, including many genes involved in DNA repair. Conversely, our results show that CDK12 inhibition promotes the expression of short genes with few exons, including many growth-promoting genes regulated by the AP-1 and NF-κB transcription factors. Inhibition of these pathways strongly synergize with CDK12 inhibitors to suppress melanoma growth, suggesting promising drug combinations for more effective melanoma treatment.

Perspective: Human Milk Composition and Related Data for National Health and Nutrition Monitoring and Related Research.

National health and nutrition monitoring is an important federal effort in the United States and Canada, and the basis for many of their nutrition and health policies. Understanding of child exposures through human milk (HM) remains out of reach due to lack of current and representative data on HM's composition and intake volume. This article provides an overview of the current national health and nutrition monitoring activities for HM-fed children, HM composition (HMC) and volume data used for exposure assessment, categories of potential measures in HM, and associated variability factors. In this Perspective, we advocate for a framework for collection and reporting of HMC data for national health and nutrition monitoring and programmatic needs, including a shared vision for a publicly available Human Milk Composition Data Repository (HMCD-R) to include essential metadata associated with HMC. HMCD-R can provide a central, integrated platform for researchers and public health officials for compiling, evaluating, and sharing HMC data. The compiled compositional and metadata in HMCD-R would provide pertinent measures of central tendency and variability and allow use of modeling techniques to approximate compositional profiles for subgroups, providing more accurate exposure assessments for purposes of monitoring and surveillance. HMC and related metadata could facilitate understanding the complexity and variability of HM composition, provide crucial data for assessment of infant and maternal nutritional needs, and inform public health policies, food and nutrition programs, and clinical practice guidelines.

Sex Differences in Subsequent Falls and Falls Risk: A Prospective Cohort Study in Older Adults.

BACKGROUND: Sex differences for subsequent falls and falls risk factors in community-dwelling older adults who have fallen are unknown. Our aim was to: (1) compare the number of falls between sexes, (2) identify modifiable falls risk factors, and (3) explore the interaction of sex on falls risk factors in older adults who fall. METHODS: Four hundred sixty-two community dwellers seeking medical attention after an index fall were recruited from the Vancouver Falls Prevention Clinic and participated in this 12-month prospective cohort study. Ninety-six participants were part of a randomized controlled trial of exercise. Falls were tracked with monthly falls calendars. Demographics, falls risk measures, and the number of subsequent falls were compared between sexes. A principal component analysis (PCA) was employed to reduce the falls risk measures to a smaller set of factors. The PCA factors were used in negative binomial regression models to predict the number of subsequent falls. Age, exposure time (i.e., number of falls monitoring days), and prescribed exercise (yes/no) were used as covariates, and sex (male/female) and PCA factors were used as main effects. The interaction of sex by PCA factor was then included. RESULTS: Males fell more over 12 months (males: 2.80 ± 6.86 falls; females: 1.25 ± 2.63 falls) than females, and poorer executive function predicted falls in males. Four PCA factors were defined - impaired cognition and mobility, low mood and self-efficacy, mobility resilience, and perceived poor health - each predicted the number of falls. The sex by mobility resilience interaction suggested that mobility resilience was less protective of falls in males. CONCLUSION: Modifiable risk factors related to cognition, physical function, psychological wellbeing, and health status predicted subsequent falls. In males, better mobility was not as protective of falls compared with females. This may be due to males' poorer executive function, contributing to decreased judgement or slowed decision-making during mobility. These results may inform efficacious sex-specific falls prevention strategies.

Organoids in Lung Cancer Management.

Lung cancer is a complex milieu of genomically altered cancer cells, a diverse collection of differentiated cells and nonneoplastic stroma. Lung cancer organoids is a three-dimensional structure grown from patient cancer tissue that could mimic in vivo complex behavior and cellular architecture of the cancer. Furthermore, the genomic alterations of the primary lung tumor is captured ex vivo. Lung cancer organoids have become an important preclinical model for oncology studies in recent years. It could be used to model the development of lung cancer, investigate the process of tumorigenesis, and also study the signaling pathways. The organoids could also be a platform to perform drug screening and biomarker validation of lung cancer, providing a promising prediction of patient-specific drug response. In this review, we described how lung cancer organoids have opened new avenues for translating basic cancer research into clinical therapy and discussed the latest and future developments in organoid technology, which could be further applied in lung cancer organoids research.

Massive haplotypes underlie ecotypic differentiation in sunflowers.

Species often include multiple ecotypes that are adapted to different environments1. However, it is unclear how ecotypes arise and how their distinctive combinations of adaptive alleles are maintained despite hybridization with non-adapted populations2-4. Here, by resequencing 1,506 wild sunflowers from 3 species (Helianthus annuus, Helianthus petiolaris and Helianthus argophyllus), we identify 37 large (1-100 Mbp in size), non-recombining haplotype blocks that are associated with numerous ecologically relevant traits, as well as soil and climate characteristics. Limited recombination in these haplotype blocks keeps adaptive alleles together, and these regions differentiate sunflower ecotypes. For example, haplotype blocks control a 77-day difference in flowering between ecotypes of the silverleaf sunflower H. argophyllus (probably through deletion of a homologue of FLOWERING LOCUS T (FT)), and are associated with seed size, flowering time and soil fertility in dune-adapted sunflowers. These haplotypes are highly divergent, frequently associated with structural variants and often appear to represent introgressions from other-possibly now-extinct-congeners. These results highlight a pervasive role of structural variation in ecotypic adaptation.

Feasibility of image registration and fusion for evaluation of structure and perfusion of the entire second trimester placenta by three-dimensional power Doppler ultrasound.

BACKGROUND: Placental perfusion can be evaluated by 3D power Doppler ultrasound (3D PD-US), particularly using the validated tool 3D Fractional Moving Blood Volume (3D-FMBV); however regional variability and size limitations beyond the first trimester mean that multiple 3D PD-US volumes are required to evaluate the whole organ. PURPOSE: We assessed the feasibility of manual offline stitching of second trimester 3D PD-US volumes of the placenta to assess whole organ perfusion using 3D-FMBV. MATERIALS AND METHODS: This was a single-centre, prospective, observational cohort study of 36 normal second trimester singleton pregnancies with anterior placentas. 3D PD-US placental volumes were manually segmented offline and stitched together by rigid registration using manually selected, pair-wise coordinates. Data acquisition and offline volume segmentation and stitching were triplicated by a single observer with Dice similarity coefficient (DSC) and Hausdorff distance used to assess consistency. Intraclass correlation coefficient (ICC) was used to assess intra-observer repeatability of 3D-FMBV and placental volume. RESULTS: Acquisition and stitching success were 94% and 88%, respectively. Median time for acquisition, segmentation and stitching were 13 min, 40 min and 95 min, respectively. Median intra-observer DSCs were 0.94 and 0.88, and Hausdorff distances were 11.85 mm and 36.6 mm, for segmentations and stitching, respectively. CONCLUSION: 3D-ultrasound volume stitching of the placenta is technically feasible. Intra-observer repeatability was good to excellent for all measured parameters. This work demonstrates technical feasibility; further studies may provide the basis of an in-vivo assessment tool to measure the placenta in mid-to late pregnancy.

Geriatrician-led evidence-based Falls Prevention Clinic: a prospective 12-month feasibility and acceptability cohort study among older adults.

OBJECTIVE: We assessed the feasibility and acceptability of delivering a geriatrician-led evidence-based Falls Prevention Clinic to older adults with a history of falls. DESIGN: 12-month prospective cohort study. SETTING: Vancouver Falls Prevention Clinic, Vancouver, British Columbia, Canada (www.fallsclinic.ca). PARTICIPANTS: 188 community-dwelling older adults aged ≥70 years who received a baseline assessment at the Vancouver Falls Prevention Clinic due to having had at least one fall resulting in medical attention in the previous 12 months. Fifty-six per cent of participants were also participating in a randomised controlled trial. MEASUREMENTS: Feasibility was ascertained by measuring demand (clinic attendance). Acceptability was measured by compliance with recommendations, completion of monthly fall calendars and patient experience. RESULTS: The attendance was 65% of those eligible and invited. This indicates feasibility for demand. 155 received at least one of the following clinical management recommendations from four domains (compliance reported in %): (1) medication changes (78%); (2) exercise prescription (58%); (3) referrals to other healthcare professionals (78%); and/or (4) lifestyle modifications (35%) excluding exercise. Overall compliance to all recommendations was 69%. Patient experience was related to factors impacting patient perceived physical benefit and attributes influencing patient satisfaction. CONCLUSION: This study demonstrated the feasibility and acceptability of a multifactorial intervention approach based on best available evidence-based medicine.

Low 25-hydroxyvitamin D levels are more prevalent in Canadians of South Asian than European ancestry inhabiting the National Capital Region of Canada.

The US Institute of Medicine defined serum 25-hydroxyvitamin D (25OHD) cut point values of 30 nmol/L and 40 nmol/L were used to assess the vitamin D status of South Asian and European Canadians of self-identified ancestry living in the National Capital Region of Canada. Serum 25OHD values were measured in the spring and fall of 2012 to represent status during the winter and summer months, respectively. A total of 1238 measurements were obtained from 669 participants (49% South Asian ancestry): some participants were measured only once (spring or fall). Median 25OHD values were significantly higher in participants of European ancestry: 70.8 nmol/L (68.1, 73.5; 95% CI) versus South Asian ancestry: 42.7 nmol/L (40.5, 45.0; P<0.001). Spring vs. fall differences were small for each ethnic group and significant only for those of European ancestry (2.9, CI: 1.0-4.9 nmol/L; P = 0.01). Among participants of South Asian ancestry, 27.3% (fall) and 29.1% (spring) of females had values <40 nmol/L while the percentages for males were considerably higher (36.5% and 44.2%, respectively). The corresponding values for participants of European ancestry were ≤10%, showing that the South Asian participants were less likely to achieve the 25OHD concentrations established by the IOM for optimum bone health. Investigation of the factors related to serum 25OHD levels showed that supplement intake and ethnic background were associated with the biggest differences. Skin color was not a major factor, suggesting that genetic factors are responsible for the observed differences between participants of different ethnic backgrounds.

Sustained Effects of Memory and Lifestyle Interventions on Memory Functioning of Older Adults: An 18-Month Follow-Up Study.

Background: There has been much research devoted to examining the short-term effects of different interventions for improving memory functioning of older adults with memory complaints. Nevertheless, very few studies have examined the long-term effects of these interventions. Thus, the present study compared the sustained effects of a conventional memory intervention (MI) and a Chinese lifestyle intervention on improving memory functioning in older adults. Methods: Twenty-nine older adults who were aged 60 years and older and had memory complaints were recruited. Each completed 10 weekly sessions of the Dejian Mind-body Intervention (DMBI; n = 11) or MI (n = 18) approximately 18 months ago. Participants' verbal and visual memory functioning and their subjective impression of the changes of their memory performance and physical and psychological health status were evaluated. Results: Results showed significant improvements in memory in both intervention groups at the follow-up assessments when compared with baseline. In addition, older adults in both intervention groups perceived improved memory performance and physical and psychological wellness at follow-up, with the DMBI group reporting significantly greater improvements in physical health compared to the MI group. Conclusion: Altogether, the present study provides supportive evidence that the DMBI and MI might be two effective remedies for older adults to improve or preserve their memory functioning with relatively sustained effects.

Frontal Underactivation During Working Memory Processing in Adults With Acute Partial Sleep Deprivation: A Near-Infrared Spectroscopy Study.

Individuals with partial sleep deprivation may have working memory (WM) impairment, but the underlying neural mechanism of this phenomenon is relatively unknown. The present study examined neural processing during WM performance in individuals with and without partial sleep deprivation using near-infrared spectroscopy (NIRS). Forty college students (10 males) were equally split into Sufficient Sleep (SS) and Insufficient Sleep (IS) groups based on self-reports of previous night's sleep duration. Participants in the SS group obtained the recommended amounts of sleep according to various sleep organizations (i.e., >7.0 h), whereas those in the IS group obtained amounts of sleep no greater than the lower limit of the recommendation (i.e., ≤7.0 h). All participants underwent an n-back paradigm with a WM load (i.e., 3-back) and a control condition (i.e., 0-back) while their prefrontal hemodynamics were recorded by NIRS. The IS and SS groups performed the tasks comparably well. However, unlike the SS group, which exhibited bilateral frontal activation indicated by increased oxyhemoglobin concentration and decreased deoxyhemoglobin concentration during WM processing (i.e., 3-back > 0-back), the IS group did not exhibit such activation. In addition, levels of WM-related frontal activation, especially those on the left side, correlated with sleep duration the night before, even when habitual sleep duration was controlled for. The findings suggest the presence of frontal lobe dysfunction in the absence of evident WM difficulties in individuals with acute partial sleep deprivation. They also highlight the importance of a good night's sleep to brain health.

Sex Difference in Aerobic Exercise Efficacy to Improve Cognition in Older Adults with Vascular Cognitive Impairment: Secondary Analysis of a Randomized Controlled Trial.

Aerobic training (AT) is a promising, non-pharmacological intervention to mitigate the deleterious effects of aging and disease on brain health. However, a large amount of variation exists in its efficacy. This is a secondary analysis of a randomized controlled trial of AT in 71 older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Specifically, we investigated: 1) whether sex moderates the relationship between AT and executive functions, and 2) the role of brain derived neurotrophic factor (BDNF) and gains in functional fitness capacity. Older adults were randomly assigned to either 6-month, thrice-weekly AT or to usual care plus education (CON). At baseline, trial completion, and 6-month follow-up, executive functions were assessed with the Trail Making Test (A & B), verbal digits forward and backward test, and the Stroop Test. Functional fitness capacity was assessed with the 6-Minute Walk Test. Compared with CON, AT significantly improved Trail Making Test performance in females but not males, an effect that was retained at follow-up. AT significantly increased BDNF levels in females but decreased levels in males. On the other hand, AT led to significant gains in functional fitness capacity in males only. This study provides evidence that sex differences exist in AT efficacy on brain health as well as in the biological mechanisms subserving AT.

Corrigendum: The Impact of Aerobic Exercise on Fronto-Parietal Network Connectivity and Its Relation to Mobility: An Exploratory Analysis of a 6-Month Randomized Controlled Trial.

[This corrects the article on p. 344 in vol. 11, PMID: 28713255.].

The Impact of Aerobic Exercise on Fronto-Parietal Network Connectivity and Its Relation to Mobility: An Exploratory Analysis of a 6-Month Randomized Controlled Trial.

Impaired mobility is a major concern for older adults and has significant consequences. While the widely accepted belief is that improved physical function underlies the effectiveness of targeted exercise training in improving mobility and reducing falls, recent evidence suggests cognitive and neural benefits gained through exercise may also play an important role in promoting mobility. However, the underlying neural mechanisms of this relationship are currently unclear. Thus, we hypothesize that 6 months of progressive aerobic exercise training would alter frontoparietal network (FPN) connectivity during a motor task among older adults with mild subcortical ischemic vascular cognitive impairment (SIVCI)-and exercise-induced changes in FPN connectivity would correlate with changes in mobility. We focused on the FPN as it is involved in top-down attentional control as well as motor planning and motor execution. Participants were randomized either to usual-care (CON), which included monthly educational materials about VCI and healthy diet; or thrice-weekly aerobic training (AT), which was walking outdoors with progressive intensity. Functional magnetic resonance imaging was acquired at baseline and trial completion, where the participants were instructed to perform bilateral finger tapping task. At trial completion, compared with AT, CON showed significantly increased FPN connectivity strength during right finger tapping (p < 0.05). Across the participants, reduced FPN connectivity was associated with greater cardiovascular capacity (p = 0.05). In the AT group, reduced FPN connectivity was significantly associated with improved mobility performance, as measured by the Timed-Up-and-Go test (r = 0.67, p = 0.02). These results suggest progressive AT may improve mobility in older adults with SIVCI via maintaining intra-network connectivity of the FPN.

A Chinese Chan-based Mind-Body Intervention Improves Memory of Older Adults.

There is growing interest in the adoption of lifestyle interventions to remediate age-related declines in memory functioning and physical and psychological health among older adults. This study aimed to investigate whether a Chinese Chan-based lifestyle intervention, the Dejian Mind-Body Intervention (DMBI), leads to positive benefits for memory functioning in older adults. Fifty-six adults aged 60 years or older with subjective memory complaints (SMC) were randomly assigned to receive the DMBI or a control intervention (i.e., a conventional memory intervention; MI) once a week for 10 weeks; 48 of the adults completed the intervention. Participants' verbal and visual memory functioning before and after the intervention were compared. In addition, changes in the participants' subjective feelings about their memory performance and physical and psychological health after the intervention were examined. The results showed that both the DMBI and MI resulted in significant improvements in both verbal and visual memory functioning and that the extent of the improvements was correlated with participants' level of performance at baseline. In addition, compared to the MI group, the DMBI group had significantly greater improvements in subjective physical and psychological health after the intervention. In summary, the present findings support the potential of the DMBI as an alternative lifestyle intervention for improving memory functioning, subjective physical and psychological health of older adults with SMC.

Economic evaluation of aerobic exercise training in older adults with vascular cognitive impairment: PROMoTE trial.

BACKGROUND/OBJECTIVES: Evidence suggests that aerobic exercise may slow the progression of subcortical ischaemic vascular cognitive impairment (SIVCI) by modifying cardiovascular risk factors. Yet the economic consequences relating to aerobic training (AT) remain unknown. Therefore, our primary objective was to estimate the incremental cost per quality-adjusted life years (QALYs) gained of a thrice weekly AT intervention compared with usual care. DESIGN: Cost-utility analysis alongside a randomised trial. SETTING: Vancouver, British Columbia, Canada. PARTICIPANTS: 70 adults (mean age of 74 years, 51% women) who meet the diagnostic criteria for mild SIVCI. INTERVENTION: A 6-month, thrice weekly, progressive aerobic exercise training programme compared with usual care (CON; comparator) with a follow-up assessment 6 months after formal cessation of aerobic exercise training. MEASUREMENTS: Healthcare resource usage was estimated over the 6-month intervention and 6-month follow-up period. Health status (using the EQ-5D-3L) at baseline and trial completion and 6-month follow-up was used to calculate QALYs. The incremental cost-utility ratio (cost per QALY gained) was calculated. RESULTS: QALYs were both modestly greater, indicating a health gain. Total healthcare costs (ie, 1791±1369 {2015 $CAD} at 6 months) were greater, indicating a greater cost for the thrice weekly AT group compared with CON. From the Canadian healthcare system perspective, the incremental cost-utility ratios for thrice weekly AT were cost-effective compared with CON, when using a willingness to pay threshold of $CAD 20 000 per QALY gained or higher. CONCLUSIONS: AT represents an attractive and potentially cost-effective strategy for older adults with mild SIVCI. TRIAL REGISTRATION NUMBER: NCT01027858.

Slow Processing Speed Predicts Falls in Older Adults With a Falls History: 1-Year Prospective Cohort Study.

BACKGROUND/OBJECTIVES: A previous fall is a strong predictor of future falls. Recent epidemiologic data suggest that deficits in processing speed predict future injurious falls. Our primary objective was to determine a parsimonious predictive model of future falls among older adults who experienced ≥1 fall in the past 12 months based on the following categories: counts of (1) total, (2) indoor, (3) outdoor or (4) non-injurious falls; (5) one mild or severe injury fall (yes vs no); (6) an injurious instead of a non-injurious fall; and (7) an outdoor instead of an indoor fall. DESIGN: 12-month prospective cohort study. SETTING: Vancouver Falls Prevention Clinic, Canada (www.fallsclinic.ca). PARTICIPANTS: Two-hundred and eighty-eight community-dwelling older adults aged ≥70 years with a history of ≥1 fall resulting in medical attention in the previous 12 months. MEASUREMENTS: We employed principal component analysis to reduce the baseline predictor variables to a smaller set of five factors (i.e., processing speed, working memory, emotional functioning, physical functioning and body composition/fall risk profile). Second, we used the extracted five factors as predictors in regression models predicting the incidence of falls over a 12-month prospective observation period. We conducted regression analyses for the seven falls-related categories (defined above). RESULTS: Among older adults with a falls history, processing speed was the most consistent predictor of future falls; poorer processing speed predicted a greater number of total, indoor, outdoor, and non-injurious falls, and a greater likelihood of experiencing at least one mild or severe injurious fall (all P values < .01). CONCLUSION: Poorer performance on the processing speed factor, a trainable factor, was independently associated with the most costly type of falls-injurious falls.

Distinct Cytokine and Chemokine Profiles in Autism Spectrum Disorders.

Previous studies have shown that immunological factors are involved in the pathogenesis of autism spectrum disorders (ASDs). However, this research has been conducted almost exclusively in Western contexts, and only a handful of studies on immune measures have been conducted in Asian populations, such as Chinese populations. The present study examined whether immunological abnormalities are associated with cognitive deficits and problem behaviors in Chinese children with ASD and whether these children show different immunological profiles. Thirteen typically developing (TD) children and 22 children with ASD, aged 6-17 years, participated voluntarily in the study. Executive functions and short-term memory were measured using neuropsychological tests, and behavioral measures were assessed using parent ratings. The children were also assessed on immunological measures, specifically, the levels of cytokines and chemokines in the blood serum. Children with ASD showed greater deficits in cognitive functions, as well as altered levels of immunological measures, including CCL2, CCL5, and CXCL9 levels, compared to TD children, and the cognitive functions and associated behavioral deficits of children with ASD were significantly associated with different immunological measures. The children were further sub-classified into ASD with only autistic features (ASD-only) or ASD comorbid with attention deficit hyperactivity disorder (ASD + ADHD). The comorbidity results showed that there were no differences between the two groups of ASD children in any of the cognitive or behavioral measures. However, the results pertaining to immunological measures showed that the children with ASD-only and ASD + ADHD exhibited distinct cytokine and chemokine profiles and that abnormal immunologic function was associated with cognitive functions and inattention/hyperactivity symptoms. These results support the notion that altered immune functions may play a role in the selective cognitive and behavioral symptoms of ASD.

Are the EQ-5D-3L and the ICECAP-O responsive among older adults with impaired mobility? Evidence from the Vancouver Falls Prevention Cohort Study.

PURPOSE: Preference-based generic measures are gaining increased use in mobility research to assess health-related quality of life and wellbeing. Hence, we examined the responsiveness of these two measures among individuals at risk of mobility impairment among adults aged ≥70 years. METHODS: We conducted a 12-month prospective cohort study of community-dwelling older adults (n = 288 to n = 341 depending on analysis) who were seen at the Vancouver Falls Prevention Clinic who had a history of at least one fall in the previous 12 months. We compared the responsiveness of the EuroQol-5 Domain-3 Level (EQ-5D-3L) and the index of capability for older adults (ICECAP-O) by examining changes in these measures over time (i.e., over 6 and 12 months) and by examining whether their changes varied as a function of having experienced 2 or more falls over 6 and 12 months. RESULTS: Only the ICECAP-O showed a significant change over time from baseline through 12 months; however, neither measure showed change that exceeded the standard error of the mean. Both measures were responsive to falls that occurred during the first 6 months of the study (p < .05). These effects appeared to be amplified among individuals identified as having mild cognitive impairment (MCI) at baseline (p < .01). Additionally, the EQ-5D-3L was responsive among fallers who did not have MCI as well as individuals with MCI who did not fall (p < .05). CONCLUSION: This study provides initial evidence suggesting that the EQ-5D-3L is generally more responsive, particularly during the first 6 months of falls tracking among older adults at risk of future mobility impairment.

Can the Otago falls prevention program be delivered by video? A feasibility study.

OBJECTIVES: We assessed the feasibility of delivering the Otago Exercise Programme (OEP) via an interactive DVD (ie, OEP-DVD) in combination with monthly physical therapist phone calls to older adults. DESIGN: This pre-post (baseline and 6-month follow-up) study included an intervention group (n=61) based in a rural location and a control group (n=21) based in a city. SETTING: Sechelt and Vancouver, British Columbia. PARTICIPANTS: 82 community-dwelling adults ≥75 years. INTERVENTION: Individuals in the intervention group received the OEP-DVD and were instructed to do the exercises 3 times a week after their initial home physical therapist visit for 6 months. PRIMARY AND SECONDARY OUTCOMES: Feasibility was ascertained by withdrawal rate and compliance to the OEP-DVD. The number of participants and the frequency (ie, number of times weekly) they performed the OEP exercises and walking were used to estimate compliance. The potential benefit of the OEP-DVD on falls risk profile (Physiological Profile Assessment (PPA)) and mobility were examined by comparing the change in the intervention group compared with the control group. Self-reported compliance to the exercise programme was assessed by monthly returned diary. RESULTS: Of the 82 participants, 2 withdrew from the OEP-DVD group and none withdrew from the control group. We obtained compliance data on 72% of participants in the intervention group. The mean OEP-DVD compliance was 87% and the mean walking compliance was 166%. After adjusting for baseline PPA, baseline age, sex, baseline comorbidities, baseline cognitive status and baseline falls-related self-efficacy, there was a significant between-group improvement in the overall PPA score (OEP group pre-PPA to post-PPA score: 0.79±1.2 to 0.7±0.9; p<0.05) at study completion. CONCLUSIONS: Although the OEP-DVD resulted in significant reductions in falls risk among community-dwelling older adults, there was a notable loss to follow-up limiting the feasibility of this approach.

Aerobic exercise and vascular cognitive impairment: A randomized controlled trial.

OBJECTIVE: To assess the efficacy of a progressive aerobic exercise training program on cognitive and everyday function among adults with mild subcortical ischemic vascular cognitive impairment (SIVCI). METHODS: This was a proof-of-concept single-blind randomized controlled trial comparing a 6-month, thrice-weekly, progressive aerobic exercise training program (AT) with usual care plus education on cognitive and everyday function with a follow-up assessment 6 months after the formal cessation of aerobic exercise training. Primary outcomes assessed were general cognitive function (Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog]), executive functions (Executive Interview [EXIT-25]), and activities of daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]). RESULTS: Seventy adults randomized to aerobic exercise training or usual care were included in intention-to-treat analyses (mean age 74 years, 51% female, n = 35 per group). At the end of the intervention, the aerobic exercise training group had significantly improved ADAS-Cog performance compared with the usual care plus education group (-1.71 point difference, 95% confidence interval [CI] -3.15 to -0.26, p = 0.02); however, this difference was not significant at the 6-month follow-up (-0.63 point difference, 95% CI -2.34 to 1.07, p = 0.46). There were no significant between-group differences at intervention completion and at the 6-month follow-up in EXIT-25 or ADCS-ADL performance. Examination of secondary measures showed between-group differences at intervention completion favoring the AT group in 6-minute walk distance (30.35 meter difference, 95% CI 5.82 to 54.86, p = 0.02) and in diastolic blood pressure (-6.89 mm Hg difference, 95% CI -12.52 to -1.26, p = 0.02). CONCLUSIONS: This study provides preliminary evidence for the efficacy of 6 months of thrice-weekly progressive aerobic training in community-dwelling adults with mild SIVCI, relative to usual care plus education. CLINICALTRIALSGOV IDENTIFIER: NCT01027858. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for adults with mild SIVCI, an aerobic exercise program for 6 months results in a small, significant improvement in ADAS-Cog performance.