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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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), or ii. 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) [ABSTRACT FROM AUTHOR]