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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: Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood.Objective: The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD.Methods: This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05.Results: After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (β  = -0.29, p = 0.037) and poorer working memory (β= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p > 0.132).Conclusion: Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function. [ABSTRACT FROM AUTHOR]

• Fallers with MCI had a greater level of disruptive DMN-SMN connectivity. • DMN-SMN connectivity increased linearly from Fallers only – MCI only – Fallers + MCI. • Fallers with MCI have significantly greater postural sway than those without MCI. • Postural sway increased linearly from Fallers only - MCI only - Fallers + MCI. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. • Maintaining physical and cognitive function is critical for healthy aging. • Physical function and cognitive function are linked and share common mechanisms. • Exercise training improves physical function and cognitive function. • Exercise-induced improvements in physical and cognitive function are associated. [ABSTRACT FROM AUTHOR]