An Individualized Tractography Pipeline for the Nucleus Basalis of Meynert Lateral Tract.

Background: At the center of the cortical cholinergic network, the nucleus basalis of Meynert (NBM) is crucial for the cognitive domains most vulnerable in PD. Preclinical evidence has demonstrated the positive impact of NBM deep brain stimulation (DBS) on cognition but early human trials have had mixed results. It is possible that DBS of the lateral NBM efferent white matter fiber bundle may be more effective at improving cognitive-motor function. However, precise tractography modelling is required to identify the optimal target for neurosurgical planning. Individualized tractography approaches have been shown to be highly effective for accurately identifying DBS targets but have yet to be developed for the NBM. Methods: Using structural and diffusion weighted imaging, we developed a tractography pipeline for precise individualized identification of the lateral NBM target tract. Using dice similarity coefficients, the reliability of the tractography outputs was assessed across three cohorts to investigate: 1) whether this manual pipeline is more reliable than an existing automated pipeline currently used in the literature; 2) the inter- and intra-rater reliability of our pipeline in research scans of patients with PD; and 3) the reliability and practicality of this pipeline in clinical scans of DBS patients. Results: The individualized manual pipeline was found to be significantly more reliable than the existing automated pipeline for both the segmentation of the NBM region itself (p<0.001) and the reconstruction of the target lateral tract (p=0.002). There was also no significant difference between the reliability of two different raters in the PD cohort (p=0.25), which showed high inter- (mean Dice coefficient >0.6) and intra-rater (mean Dice coefficient >0.7) reliability across runs. Finally, the pipeline was shown to be highly reliable within the clinical scans (mean Dice coefficient = 0.77). However, accurate reconstruction was only evident in 7/10 tracts. Conclusion: We have developed a reliable tractography pipeline for the identification and analysis of the NBM lateral tract in research and clinical grade imaging of healthy young adult and PD patient scans.

Resistance Training Maintains White Matter and Physical Function in Older Women with Cerebral Small Vessel Disease: An Exploratory Analysis of a Randomized Controlled Trial.

Background: As the aging population grows, there is an increasing need to develop accessible interventions against risk factors for cognitive impairment and dementia, such as cerebral small vessel disease (CSVD). The progression of white matter hyperintensities (WMHs), a key hallmark of CSVD, can be slowed by resistance training (RT). We hypothesize RT preserves white matter integrity and that this preservation is associated with improved cognitive and physical function. Objective: To determine if RT preserves regional white matter integrity and if any changes are associated with cognitive and physical outcomes. Methods: Using magnetic resonance imaging data from a 12-month randomized controlled trial, we compared the effects of a twice-weekly 60-minute RT intervention versus active control on T1-weighted over T2-weighted ratio (T1w/T2w; a non-invasive proxy measure of white matter integrity) in a subset of study participants (N = 21 females, mean age = 69.7 years). We also examined the association between changes in T1w/T2w with two key outcomes of the parent study: (1) selective attention and conflict resolution, and (2) peak muscle power. Results: Compared with an active control group, RT increased T1w/T2w in the external capsule (p = 0.024) and posterior thalamic radiations (p = 0.013) to a greater degree. Increased T1w/T2w in the external capsule was associated with an increase in peak muscle power (p = 0.043) in the RT group. Conclusion: By maintaining white matter integrity, RT may be a promising intervention to counteract the pathological changes that accompany CSVD, while improving functional outcomes such as muscle power.

No laughing white matter: Reduced integrity of the cortical cholinergic pathways in Parkinson's disease-related cognitive impairment.

BACKGROUND: Approximately one third of recently diagnosed Parkinson's disease (PD) patients experience cognitive decline. The nucleus basalis of Meynert (NBM) degenerates early in PD and is crucial for cognitive function. The two main NBM white matter pathways include a lateral and medial trajectory. However, research is needed to determine which pathway, if any, are associated with PD-related cognitive decline. METHODS: Thirty-seven PD patients with no mild cognitive impairment (MCI) were included in this study. Participants either developed MCI at 1-year follow up (PD MCI-Converters; n = 16) or did not (PD no-MCI; n = 21). Mean diffusivity (MD) and fractional anisotropy (FA) of the medial and lateral NBM tracts were extracted using probabilistic tractography. Between-group differences in MD and FA for each tract was compared using ANCOVA, controlling for age, sex, and disease duration. Control comparisons of the internal capsule MD and FA were also performed. Associations between baseline MD or FA and cognitive outcomes (working memory, psychomotor speed, delayed recall, and visuospatial function) were assessed using linear mixed models. RESULTS: PD MCI-Converters had significantly greater MD and lower FA (p < .001) of both NBM tracts compared to PD no-MCI. No difference was found in the MD (p = .06) or FA (p = .31) of the control region. Trends were identified between: 1) lateral tract MD and FA with working memory decline; and 2) medial tract MD and reduced psychomotor speed. CONCLUSIONS: Reduced integrity of the NBM tracts is evident in PD patients up to one year prior to the development of MCI. Thus, deterioration of the NBM tracts in PD may be an early marker of those at risk of cognitive decline.

No Laughing White Matter: Cortical Cholinergic Pathways and Cognitive Decline in Parkinson's Disease.

Background: Approximately one third of recently diagnosed Parkinson's disease (PD) patients experience cognitive decline. The nucleus basalis of Meynert (NBM) degenerates early in PD and is crucial for cognitive function. The two main NBM white matter pathways include a lateral and medial trajectory. However, research is needed to determine which pathway, if any, are associated with PD-related cognitive decline. Methods: Thirty-seven PD patients with no mild cognitive impairment (MCI) were included in this study. Participants either developed MCI at 1-year follow up (PD MCI-Converters; n=16) or did not (PD no-MCI; n=21). Mean diffusivity (MD) of the medial and lateral NBM tracts were extracted using probabilistic tractography. Between-group differences in MD for each tract was compared using ANCOVA, controlling for age, sex, and disease duration. Control comparisons of the internal capsule MD were also performed. Associations between baseline MD and cognitive outcomes (working memory, psychomotor speed, delayed recall, and visuospatial function) were assessed using linear mixed models. Results: PD MCI-Converters had significantly greater MD of both NBM tracts compared to PD no-MCI (p<.001). No difference was found in the control region (p=.06). Trends were identified between: 1) lateral tract MD, poorer visuospatial performance (p=.05) and working memory decline (p=.04); and 2) medial tract MD and reduced psychomotor speed (p=.03). Conclusions: Reduced integrity of the NBM tracts is evident in PD patients up to one year prior to the development of MCI. Thus, deterioration of the NBM tracts in PD may be an early marker of those at risk of cognitive decline.

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function.

BACKGROUND: Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms. METHODS: Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up). DISCUSSION: Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as "medicine" to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016.

Weight for It: Resistance Training Mitigates White Matter Hyperintensity-Related Disruption to Functional Networks in Older Females.

BACKGROUND: White matter hyperintensities (WMH) are associated with impaired cognition and increased falls risk. Resistance training (RT) is a promising intervention to reduce WMH progression, improve executive functions, and reduce falls. However, the underlying neurobiological process by which RT improves executive functions and falls risk remain unclear. We hypothesized that: 1) RT reduces the level of WMH-related disruption to functional networks; and 2) reduced disruption to the sensorimotor and attention networks will be associated with improved executive function and reduced falls risk. OBJECTIVE: Investigate the impact of 52 weeks of RT on WMH-related disruption to functional networks. METHODS: Thirty-two older females (65-75 years) were included in this exploratory analysis of a 52-week randomized controlled trial. Participants received either twice-weekly RT or balance and tone training (control). We used lesion network mapping to assess changes in WMH-related disruption to the sensorimotor, dorsal attention, and ventral attention networks. Executive function was measured using the Stroop Colour-Word Test. Falls risk was assessed using the Physiological Profile Assessment (PPA) and the foam sway test. RESULTS: RT significantly reduced the level of WMH-related disruption to the sensorimotor network (p = 0.012). Reduced disruption to the dorsal attention network was associated with improvements in Stroop performance (r = 0.527, p = 0.030). Reduced disruption to the ventral attention network was associated with reduced PPA score (r = 0.485, p = 0.049)Conclusion:RT may be a promising intervention to mitigate WMH-related disruption to the sensorimotor network. Additionally, reducing disruption to the dorsal and ventral attention networks may contribute to improved executive function and reduced falls risk respectively.

Mind the gaps: functional networks disrupted by white matter hyperintensities are associated with greater falls risk.

White matter hyperintensities (WMH) are associated with greater falls risk and slow gait speed. Whether these deficits are caused by the disruption of large-scale functional networks remains inconclusive. Further, physical activity moderates the association between WMHs and falls, but whether this extends to the disruption of functional networks remains unknown. One hundred and sixty-four adults (>55 years old) were included in this study. Using lesion network mapping, we identified significant correlations between the percentage of WMH-related disruption of the dorsal attention network and Physiological Profile Assessment (PPA) score (r = 0.24, p < 0.01); and between disruption of both the sensorimotor (r = 0.23, p < 0.01) and ventral attention networks (r = 0.21, p = 0.01) with foam sway. There were no significant associations with floor sway or gait speed. Physical activity moderated the association between the dorsal attention network and PPA score (p = 0.045). Thus, future research should investigate whether physical activity should be recommended in the clinical management of older adults with cerebral small vessel disease.

Sweat the Fall Stuff: Physical Activity Moderates the Association of White Matter Hyperintensities With Falls Risk in Older Adults.

Background: Falls in older adults are a major public health problem. White matter hyperintensities (WMHs) are highly prevalent in older adults and are a risk factor for falls. In the absence of a cure for WMHs, identifying potential strategies to counteract the risk of WMHs on falls are of great importance. Physical activity (PA) is a promising countermeasure to reduce both WMHs and falls risk. However, no study has yet investigated whether PA attenuates the association of WMHs with falls risk. We hypothesized that PA moderates the association between WMHs and falls risk. Methods: Seventy-six community-dwelling older adults aged 70-80 years old were included in this cross-sectional study. We indexed PA using the Physical Activity Score for the Elderly (PASE) Questionnaire. Falls risk was assessed using the Physiological Profile Assessment (PPA), and WMH volume (mm3) was determined by an experienced radiologist on T2-weighted and PD-weighted MRI scans. We first examined the independent associations of WMH volume and PASE score with PPA. Subsequently, we examined whether PASE moderated the relationship between WMH volume and PPA. We plotted simple slopes to interpret the interaction effects. Age, sex, and Montreal Cognitive Assessment (MoCA) score were included as covariates in all models. Results: Participants had a mean age of 74 years (SD = 3 years) and 54 (74%) were female. Forty-nine participants (66%) had a Fazekas score of 1, 19 (26%) had a score of 2, and 6 (8%) a score of 3. Both PASE (ß = -0.26 ± 0.11; p = 0.022) and WMH volume (ß = 0.23 ± 0.11; p = 0.043) were each independently associated with PPA score. The interaction model indicated that PASE score moderated the association between WMH volume and PPA (ß = -0.27 ± 0.12; p = 0.030), whereby higher PASE score attenuated the association between WMHs and falls risk. Conclusion: PA is an important moderator of falls risk. Importantly, older adults with WMH can reduce their risk of falls by increasing their PA.

Painting by lesions: White matter hyperintensities disrupt functional networks and global cognition.

White matter hyperintensities (WMH) are a prominent feature of cerebral small vessel disease and are associated with cognitive impairment. These deficits in cognition may be caused by the disruption of large-scale functional networks due to the presence of WMHs. However, knowledge regarding the relevance of these lesions on functional networks remains inconclusive. These inconsistencies may derive from issues with interpreting functional imaging data from clinical populations. Lesion network mapping is a technique that allows the overlaying of lesions from a patient population to the functional connectivity of a human connectome derived from healthy adults. This allows researchers to identify functional networks that would be disrupted in a healthy population should the WMHs seen in cerebral small vessel disease be present. We hypothesized that the extent to which these functional networks are disrupted by WMHs is associated with cognitive performance in older adults with cerebral small vessel disease. This cross-sectional study combined baseline data from four studies to create a total sample of 164 older adults (aged ≥55) from metropolitan Vancouver with cerebral small vessel disease. Using lesion network mapping, we assessed the percentage overlap between voxels functionally connected with both the WMHs (lesion network) and five common functional networks: (1) visual; (2) dorsal attention; (3) ventral attention; (4) sensorimotor; and (5) frontoparietal. Cognition was assessed using: (1) Montreal Cognitive Assessment (MoCA); (2) Stroop Colour Word Test (3-2); (3) Trail Making Tests (Part B-A); and (4) Digit Symbol Substitution Test. A One-Way ANOVA and Tukey post-hoc tests were performed to identify the functional networks with greatest percentage overlap with the lesion network. Partial correlations controlling for age were used to analyse whether the extent of the overlap between the lesion and functional networks was associated with poorer cognition. The visual, ventral attention, and frontoparietal networks had significantly greater overlap with the lesion network. After controlling for multiple comparisons, level of lesion network overlap with both the sensorimotor network (p<.001) and ventral attention network (p <. 001) was significantly correlated with MoCA score. Thus, the greater the disruption to the sensorimotor and ventral attention networks, the poorer the global cognition. Our results reveal that the visual, ventral attention, and frontoparietal networks are most vulnerable to disruptions stemming from WMHs. Additionally, we identified that disruption to the sensorimotor and ventral attention networks, as a result of WMHs, may underlie deficits in global cognition in older adults with cerebral small vessel disease.

Reshaping the path of vascular cognitive impairment with resistance training: a study protocol for a randomized controlled trial.

BACKGROUND: Subcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. Importantly, SIVCI is considered the most treatable form of cognitive impairment in older adults, due to its modifiable risk factors such as hypertension, diabetes mellitus, and hypercholesterolemia. Exercise training is a promising intervention to delay the progression of SIVCI, as it actively targets these cardiometabolic risk factors. Despite the demonstrated benefits of resistance training on cognitive function and emerging evidence suggesting resistance training may reduce the progression of white matter hyperintensities (WMHs), research on SIVCI has predominantly focused on the use of aerobic exercise. Thus, the primary aim of this proof-of-concept randomized controlled trial is to investigate the efficacy of a 12-month, twice-weekly progressive resistance training program on cognitive function and WMH progression in adults with SIVCI. We will also assess the efficiency of the intervention. METHODS: Eighty-eight community-dwelling adults, aged > 55 years, with SIVCI from metropolitan Vancouver will be recruited to participate in this study. SIVCI will be determined by the presence of cognitive impairment (Montreal Cognitive Assessment < 26) and cerebral small vessel disease using computed tomography or magnetic resonance imaging. Participants will be randomly allocated to a twice-weekly exercise program of (1) progressive resistance training or (2) balance and tone training (i.e., active control). The primary outcomes are cognitive function measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-13 with additional cognitive tests) and WMH progression. DISCUSSION: The burden of SIVCI is immense, and to our knowledge, this will be the first study to quantify the effect of progressive resistance training on cognitive function and WMH progression among adults with SIVCI. Slowing the rate of cognitive decline and WMH progression could preserve functional independence and quality of life. This could lead to reduced health care costs and avoidance of early institutional care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02669394 . Registered on February 1, 2016.

Shining the Light on the MotionWatch8 Light Sensor for Sleep and Aging Research: What Can We Measure and What Are We Missing?

BACKGROUND: Poor sleep is common among older adults at risk for dementia and may be due to circadian dysregulation. Light is the most important external stimulus to the circadian clock and bright light therapy (BLT) has been used for >20 years to help realign circadian rhythms. However, the ability of field methods (e.g., actigraphy) to accurately determine the type and intensity of light is unknown. OBJECTIVE: We examined the ability of the MotionWatch8 (MW8) light sensor to determine: 1) light versus dark, 2) electrical light versus daylight, and 3) device-based BLT versus light which was not BLT. METHODS: We tested the MW8 under 17 daily light scenarios. Light exposure data was collected for 5 minutes during each scenario. Concurrently, we measured light exposure using the LT40 Light Meter, a sensitive measure of light intensity. We then developed individual cut-points using receiver operator characteristics analyses to determine optimal MW8 cut-points for 1) light versus dark; 2) electrical light versus daylight; and 3) light from a BLT box versus light which was not BLT. Bland-Altman plots tested the precision of the MW8 compared to the LT40. RESULTS: The MW8 accurately discriminated light versus dark (>32 lux), and electrical light versus daylight (<323 lux). However, the MW8 had poor accuracy for 1) discriminating BLT from light which was not BLT; and 2) low precision compared to the LT40. CONCLUSION: The MW8 appears to be able to discern light versus dark and electrical light versus daylight; however, there remains a need for accurate field methods capable of measuring light exposure.

Head over heels but I forget why: Disruptive functional connectivity in older adult fallers with mild cognitive impairment.

Disrupted functional connectivity has been highlighted as a neural mechanism by which impaired cognitive function and mobility co-exist in older adults with mild cognitive impairment (MCI). The objective of this study was to determine the independent and combined effects of MCI and faller status on functional connectivity of three functional networks: default mode network (DMN), fronto-parietal network (FPN) and sensorimotor network (SMN) between 4 groups of older adults: 1) Healthy; 2) MCI without Falls; 3) Fallers without MCI; and 4) Fallers with MCI. METHODS: Sixty-six adults aged 70-80 years old were included. Cognition was assessed using: 1) cognitive dual task; 2) Stroop Colour-Word Test; 3) Trail Making Tests (TMT); and 4) Digit Symbol Substitution Test (DSST). Postural sway was assessed with eyes opened and standing on the floor. Functional connectivity was measured using fMRI while performing a finger-tapping task. RESULTS: Differences in DMN-SMN connectivity were found for Fallers with MCI vs Fallers without MCI (p = .001). Fallers with MCI had significantly greater postural sway than the other groups. Both DMN-SMN connectivity (p = .03) and postural sway (p = .001) increased in a significantly linear fashion from Fallers without MCI, to MCI without Falls, to Fallers with MCI. Participants with MCI performed significantly worse on the DSST (p = .003) and TMT (p = .007) than those without MCI. CONCLUSION: Aberrant DMN-SMN connectivity may underlie reduced postural stability. Having both impaired cognition and mobility is associated with a greater level of disruptive DMN-SMN connectivity and increased postural sway than singular impairment.

Impact of exercise training on physical and cognitive function among older adults: a systematic review and meta-analysis.

Exercise plays a key role in healthy aging by promoting both physical and cognitive function. Physical function and cognitive function appear to be interrelated and may share common mechanisms. Thus, exercise-induced improvements in physical function and cognitive function may co-occur and be associated with each other. However, no systematic review has specifically assessed and compared the effects of exercise on both physical function and cognitive function in older adults, and the association between changes in both outcomes after exercise training. Thus, we conducted a systematic review and meta-analysis (N = 48 studies) among older adults (60+ years). These data suggest exercise training has a significant benefit for both physical function (g = 0.39; p < 0.001) and cognitive function (g = 0.24; p < 0.001). At the study level, there was a positive correlation between the size of the exercise-induced effect on physical function and on cognitive function (b = 0.41; p = 0.002). Our results indicate exercise improves both physical and cognitive function, reiterating the notion that exercise is a panacea for aging well.

Nutritional labelling for healthier food or non-alcoholic drink purchasing and consumption.

BACKGROUND: Nutritional labelling is advocated as a means to promote healthier food purchasing and consumption, including lower energy intake. Internationally, many different nutritional labelling schemes have been introduced. There is no consensus on whether such labelling is effective in promoting healthier behaviour. OBJECTIVES: To assess the impact of nutritional labelling for food and non-alcoholic drinks on purchasing and consumption of healthier items. Our secondary objective was to explore possible effect moderators of nutritional labelling on purchasing and consumption. SEARCH METHODS: We searched 13 electronic databases including CENTRAL, MEDLINE and Embase to 26 April 2017. We also handsearched references and citations and sought unpublished studies through websites and trials registries. SELECTION CRITERIA: Eligible studies: were randomised or quasi-randomised controlled trials (RCTs/Q-RCTs), controlled before-and-after studies, or interrupted time series (ITS) studies; compared a labelled product (with information on nutrients or energy) with the same product without a nutritional label; assessed objectively measured purchasing or consumption of foods or non-alcoholic drinks in real-world or laboratory settings. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of bias' tool and GRADE to assess the quality of evidence. We pooled studies that evaluated similar interventions and outcomes using a random-effects meta-analysis, and we synthesised data from other studies in a narrative summary. MAIN RESULTS: We included 28 studies, comprising 17 RCTs, 5 Q-RCTs and 6 ITS studies. Most (21/28) took place in the USA, and 19 took place in university settings, 14 of which mainly involved university students or staff. Most (20/28) studies assessed the impact of labelling on menus or menu boards, or nutritional labelling placed on, or adjacent to, a range of foods or drinks from which participants could choose. Eight studies provided participants with only one labelled food or drink option (in which labelling was present on a container or packaging, adjacent to the food or on a display board) and measured the amount consumed. The most frequently assessed labelling type was energy (i.e. calorie) information (12/28).Eleven studies assessed the impact of nutritional labelling on purchasing food or drink options in real-world settings, including purchases from vending machines (one cluster-RCT), grocery stores (one ITS), or restaurants, cafeterias or coffee shops (three RCTs, one Q-RCT and five ITS). Findings on vending machines and grocery stores were not interpretable, and were rated as very low quality. A meta-analysis of the three RCTs, all of which assessed energy labelling on menus in restaurants, demonstrated a statistically significant reduction of 47 kcal in energy purchased (MD -46.72 kcal, 95% CI -78.35, -15.10, N = 1877). Assuming an average meal of 600 kcal, energy labelling on menus would reduce energy purchased per meal by 7.8% (95% CI 2.5% to 13.1%). The quality of the evidence for these three studies was rated as low, so our confidence in the effect estimate is limited and may change with further studies. Of the remaining six studies, only two (both ITS studies involving energy labels on menus or menus boards in a coffee shop or cafeteria) were at low risk of bias, and their results support the meta-analysis. The results of the other four studies which were conducted in a restaurant, cafeterias (2 studies) or a coffee shop, were not clearly reported and were at high risk of bias.Seventeen studies assessed the impact of nutritional labels on consumption in artificial settings or scenarios (henceforth referred to as laboratory studies or settings). Of these, eight (all RCTs) assessed the effect of labels on menus or placed on a range of food options. A meta-analysis of these studies did not conclusively demonstrate a reduction in energy consumed during a meal (MD -50 kcal, 95% CI -104.41, 3.88, N = 1705). We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies.Six laboratory studies (four RCTs and two Q-RCTs) assessed the impact of labelling a single food or drink option (such as chocolate, pasta or soft drinks) on energy consumed during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant difference in energy (kcal) consumed (SMD 0.05, 95% CI -0.17 to 0.27, N = 732). However, the confidence intervals were wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies.There was no evidence that nutritional labelling had the unintended harm of increasing energy purchased or consumed. Indirect evidence came from five laboratory studies that involved mislabelling single nutrient content (i.e. placing low energy or low fat labels on high-energy foods) during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant increase in energy (kcal) consumed (SMD 0.19, 95% CI -0.14to 0.51, N = 718). The effect was small and the confidence intervals wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence from these studies as very low, providing very little confidence in the effect estimate. AUTHORS' CONCLUSIONS: Findings from a small body of low-quality evidence suggest that nutritional labelling comprising energy information on menus may reduce energy purchased in restaurants. The evidence assessing the impact on consumption of energy information on menus or on a range of food options in laboratory settings suggests a similar effect to that observed for purchasing, although the evidence is less definite and also of low quality.Accordingly, and in the absence of observed harms, we tentatively suggest that nutritional labelling on menus in restaurants could be used as part of a wider set of measures to tackle obesity. Additional high-quality research in real-world settings is needed to enable more certain conclusions.Further high-quality research is also needed to address the dearth of evidence from grocery stores and vending machines and to assess potential moderators of the intervention effect, including socioeconomic status.

The effects of an 8-week computerized cognitive training program in older adults: a study protocol for a randomized controlled trial.

BACKGROUND: Given the world's aging population, it is important to identify strategies that promote healthy cognitive aging and minimize cognitive decline. Currently, no curative pharmaceutical therapy exists for cognitive impairment and dementia. As a result, there is much interest in lifestyle approaches. Specifically, complex mental activity, such as cognitive training, may be a promising method to combat cognitive decline in older adults. As such, the industry of commercial computerized cognitive training (CCT) applications has rapidly grown in the last decade. However, the efficacy of these commercial products is largely not established. Moreover, exercise is a recognized strategy for promoting cognitive outcomes in older adults and may augment the efficacy of computerized cognitive training applications. Therefore, we propose a proof-of-concept randomized controlled trial (RCT) to examine the effect of a commercial CCT program in community-dwelling older adults. METHODS: An 8-week RCT to examine the effect of a commercial CCT program, alone and preceded by a 15-min brisk walk, on cognitive function and explore the underlying neural mechanisms in adults aged 65-85 years old. Participants will be randomized to one of three intervention groups: 1) Computerized cognitive training (FBT); 2) A 15-min brisk walk followed by computerized cognitive training (Ex-FBT); or 3) A combination of educational classes, sham cognitive training, and balanced and tone exercises (active control, BAT). Participants in all intervention groups will attend three one-hour classes per week over the course of the intervention. Participants will be assessed at baseline, trial completion, and 1-year post study completion (1-year follow-up). DISCUSSION: If results from this study show benefits for cognition at trial completion, CCT programs, alone or in combination with walking, might be a strategy to promote healthy cognitive aging in older adults. In addition, results from the 1-year follow-up measurement could provide important information regarding the long-term benefits of these CCT programs. TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration System: NCT02564809; registered September 1, 2015.

Resting State Default Mode Network Connectivity, Dual Task Performance, Gait Speed, and Postural Sway in Older Adults with Mild Cognitive Impairment.

Aging is associated with an increased risk of falling. In particular, older adults with mild cognitive impairment (MCI) are more vulnerable to falling compared with their healthy counterparts. Major contributors to this increased falls risk include a decline in dual task performance, gait speed, and postural sway. Recent evidence highlights the potential influence of the default mode network (DMN), the frontoparietal network (FPN), and the supplementary motor area (SMA) on dual task performance, gait speed, and postural sway. The DMN is active during rest and deactivates during task-oriented processes, to maintain attention and stay on task. The FPN and SMA are involved in top-down attentional control, motor planning, and motor execution. The DMN shows less deactivation during task in older adults with MCI. This lack of deactivation is theorized to increase competition for resources between the DMN and task-related brain regions (e.g., the FPN and SMA), increasing distraction from the task and reducing task performance. However, no study has yet investigated the relationship between the between-network connectivity of the DMN with these regions and dual task walking, gait speed or postural sway. We hypothesized that greater functional connectivity both within the DMN and between DMN-FPN and DMN-SMA, will be associated with poorer performance during dual task walking, slower gait speed, and greater postural sway in older adults with MCI. Forty older adults with MCI were measured on a dual task-walking paradigm, gait speed over a 4-m walk, and postural sway using a sway-meter. Greater within-DMN connectivity was significantly correlated with poorer dual task performance. Furthermore, greater inter-network connectivity between the DMN and SMA was significantly correlated with slower gait speed and greater postural sway on the eyes open floor sway task. Thus, greater resting state DMN functional connectivity may be an underlying neural mechanism for reduced dual task ability, slower gait speed, and greater postural sway, resulting in the increased risk of mobility disability and falling in older adults with MCI.

The impact of nutritional labels and socioeconomic status on energy intake. An experimental field study.

There is some evidence for paradoxical effects of nutritional labelling on energy intake particularly amongst restrained eaters and those with a higher body mass index (BMI) resulting in greater consumption of energy from foods with a positive health message (e.g. "low-fat") compared with the same foods, unlabelled. This study aimed to investigate, in a UK general population sample, the likelihood of paradoxical effects of nutritional labelling on energy intake. Participants (n = 287) attended a London cinema and were offered a large tub of salted or toffee popcorn. Participants were randomised to receive their selected flavour with one of three labels: a green low-fat label, a red high-fat label or no label. Participants watched two film clips while completing measures of demographic characteristics, emotional state and taste of the popcorn. Following the experiment, popcorn consumption was measured. There were no main effects of nutritional labelling on consumption. Contrary to predictions neither BMI nor weight concern moderated the effect of label on consumption. There was a three-way interaction between low-fat label, weight concern and socioeconomic status (SES) such that weight-concerned participants of higher SES who saw a low-fat label consumed more than weight unconcerned participants of similar SES (t = -2.7, P = .04). By contrast, weight-concerned participants of lower SES seeing either type of label, consumed less than those seeing no label (t = -2.04, P = .04). Nutritional labelling may have different effects in different socioeconomic groups. Further studies are required to understand fully the possible contribution of food labelling to health inequalities.

Impact on decisions to start or continue medicines of providing information to patients about possible benefits and/or harms: a systematic review and meta-analysis.

BACKGROUND: The impact of providing information about medicines to patients on decisions about starting or continuing them is unknown. PURPOSE: To estimate the impact on decisions to start or continue medicines, of providing information to patients about possible benefits and/or harms. DATA SOURCES: Electronic searches from 1980 to October 2010; reference and citation searches of included studies. STUDY SELECTION: Two investigators assessed studies' eligibility against inclusion criteria: randomized or pseudorandomized trials; participants older than 16 years and deciding for themselves; one group received information about possible benefits and/or harms of a potentially beneficial medicine, compared with another who did not; d) a measure of decision about starting or continuing a medicine. DATA EXTRACTION: One investigator extracted all data, checked by a second. DATA SYNTHESIS: Eight studies were included, covering a range of medicines. There was no consistent impact of interventions on decisions about whether to start or continue medicines (pooled odds ratio 1.08; 95% confidence interval [CI], 0.69-1.70; P = 0.74). Among those who received more information, knowledge was increased (pooled mean difference 8.47; 95% CI 2.17-14.77; P = 0.008), and decisional conflict was reduced (pooled mean difference -0.15; 95% CI -0.24 to -0.06; P = .001). LIMITATIONS: A small number of studies across different clinical contexts, of uncertain heterogeneity, were included. CONCLUSIONS: Providing information to patients about possible benefits and/or harms has no consistent effect on the number who decide to start or continue medicines, although it increases patients' knowledge and reduces their decisional conflict.

Trial Protocol: Using genotype to tailor prescribing of nicotine replacement therapy: a randomised controlled trial assessing impact of communication upon adherence.

BACKGROUND: The behavioural impact of pharmacogenomics is untested; informing smokers of genetic test results for responsiveness to smoking cessation medication may increase adherence to this medication. The objective of this trial is to estimate the impact upon adherence to nicotine replacement therapy (NRT) of informing smokers that their oral dose of NRT has been tailored to a DNA analysis. Hypotheses to be tested are as follows: I Adherence to NRT is greater among smokers informed that their oral dose of NRT is tailored to an analysis of DNA (genotype), compared to one tailored to nicotine dependence questionnaire score (phenotype). II Amongst smokers who fail to quit at six months, motivation to make another quit attempt is lower when informed that their oral dose of NRT was tailored to genotype rather than phenotype. METHODS/DESIGN: An open label, parallel groups randomised trial in which 630 adult smokers (smoking 10 or more cigarettes daily) using National Health Service (NHS) stop smoking services in primary care are randomly allocated to one of two groups:i. NRT oral dose tailored by DNA analysis (OPRM1 gene) (genotype), orii. NRT oral dose tailored by nicotine dependence questionnaire score (phenotype)The primary outcome is proportion of prescribed NRT consumed in the first 28 days following an initial quit attempt, with the secondary outcome being motivation to make another quit attempt, amongst smokers not abstinent at six months. Other outcomes include adherence to NRT in the first seven days and biochemically validated smoking abstinence at six months. The primary outcome will be collected on 630 smokers allowing sufficient power to detect a 7.5% difference in mean proportion of NRT consumed using a two-tailed test at the 5% level of significance between groups. The proportion of all NRT consumed in the first four weeks of quitting will be compared between arms using an independent samples t-test and by estimating the 95% confidence interval for observed between-arm difference in mean NRT consumption (Hypothesis I). Motivation to make another quit attempt will be compared between arms in those failing to quit by six months (Hypothesis II). DISCUSSION: This is the first clinical trial evaluating the behavioural impact on adherence of prescribing medication using genetic rather than phenotypic information. Specific issues regarding the choice of design for trials of interventions of this kind are discussed. TRIAL DETAILS: Funder: Medical Research Council (MRC)Grant number: G0500274. ISRCTN: 14352545. Date trial stated: June 2007. Expected end date: December 2009. Expected reporting date: December 2010.

Time orientation and health-related behaviour: measurement in general population samples.

Research on health behaviour and time orientation has been hindered by a lack of consensus about appropriate measurement. Study 1 assessed the reliability of the Consideration of Future Consequences Scale (CFC) and the Zimbardo Time Perspective Inventory (ZTPI) in a general population sample (n = 300). Although more reliable, the CFC was less readable. Study 2 assessed the validity of a shortened ZTPI, measuring future and present orientation, and the full CFC. The measures had good discrimination to distinguish interpersonal differences. Construct validity of present, but not future, orientation as measured by the ZTPI, was evidenced by its mediation of the association between socioeconomic status and expectations of participating in diabetes screening. The CFC mediated this relationship more weakly. Further investigation of present orientation in understanding health-related behaviour is warranted.