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Background: Potential moderators such as exercise intensity or apolipoprotein-E4 (ApoE4) carriership may determine the magnitude of exercise effects on physical and cognitive functions in patients with dementia (PwD). We determined the effects of a 24-week aerobic and strength training program with a low- and high-intensity phase on physical and cognitive function., Methods: In an assessor-blinded randomized trial, 91 PwD (all-cause dementia, recruited from daycare and residential care facilities, age 82.3 ± 7.0 years, 59 women, Mini-Mental State Examination 20.2 ± 4.4) were allocated to the exercise or control group. In the exercise group, PwD participated in a walking and lower limb strength training program with 12 weeks low- and 12 weeks high-intensity training offered three times/week. Attention-matched control participants performed flexibility exercises and recreational activities. We assessed adherence, compliance, and exercise intensity for each session. We assessed physical (endurance, gait speed, mobility, balance, leg strength) and cognitive (verbal memory, visual memory, executive function, inhibitory control, psychomotor speed) functions with performance-based tests at baseline and after 6, 12, 18, 24, and 36 weeks (follow-up). ApoE4 carriership was determined post-intervention., Results: Sixty-nine PwD were analyzed. Their mean attendance was ~ 60% during the study period. There were no significant effects of the exercise vs. control intervention on endurance, mobility, balance, and leg strength in favor of the exercise group (Cohen's d = 0.13-0.18). Gait speed significantly improved with ~ 0.05 m/s after the high-intensity phase for exercise participants (Cohen's d = 0.41) but declined at follow-up. There were no significant effects of the exercise vs. control intervention on any of the cognitive measures (Cohen's d ~ - 0.04). ApoE4 carriership did not significantly moderate exercise effects on physical or cognitive function., Conclusions: Exercise was superior to control activities for gait speed in our sample of PwD. However, the training effect provided no protection for mobility loss after detraining (follow-up). There were no beneficial effects of the exercise vs. control group on cognitive function. Exercise intensity moderated the effects of exercise on gait speed. ApoE4 carriership moderated the effect of exercise on global cognition only (trend level)., Trial Registration: Netherlands Trial Register, NTR5035. Registered on 2 March 2015.

It is now recognized that understanding how neuroinflammation affects brain function may provide new insights into Alzheimer's pathophysiology. Tumor necrosis factor (TNF)-α, an inflammatory cytokine marker, has been implicated in Alzheimer's disease (AD), as it can impair neuronal function through suppression of long-term potentiation. Our study investigated the relationship between cerebrospinal fluid TNF-α and functional connectivity (FC) in a cohort of 64 older adults (μ age = 69.76 years; 30 cognitively normal, 34 mild AD). Higher cerebrospinal fluid TNF-α levels were associated with lower FC among brain regions important for high-level decision-making, inhibitory control, and memory. This effect was moderated by apolipoprotein E-ε4 (APOE4) status. Graph theory metrics revealed there were significant differences between APOE4 carriers at the node level, and by diagnosis at the network level suggesting global brain network dysfunction in participants with AD. These findings suggest proinflammatory mechanisms may contribute to reduced FC in regions important for high-level cognition. Future studies are needed to understand the role of inflammation on brain function and clinical progression, especially in APOE4 carriers., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: People with dementia are known to be physically frailer, more sedentary, and participate less in regular physical exercise compared to their healthy peers. Physical activity interventions have the potential to reduce the level of frailty in community-dwelling older adults. Exergaming combines physical exercise with cognitive stimulation in a virtual environment. It is an innovative and fun way of exercising, which may aid people with dementia to be more physically active. The primary aim of this study was to investigate the efficacy of a 12-week exergame training and equally long aerobic training, both compared to an active control group, on frailty in people with dementia., Design: A 3-armed randomized controlled trial compared exergame training, aerobic training, and an active control intervention., Participants: 115 people with dementia [mean (standard deviation [SD]) age = 79.2 (6.9) years; mean (SD) Mini-Mental State Examination score = 22.9 (3.4)]., Methods: Participants were randomized and individually trained 3 times a week during 12 weeks. The Evaluative Frailty Index for Physical activity (EFIP) was used to assess the level of frailty at baseline and after the 12-week intervention period. Between-group differences were analyzed with analysis of covariance., Results: The exergame group showed a trend toward higher adherence compared to the aerobic group (87.3% vs 81.1%, P = .05). A significant reduction on the EFIP was found in the exergame group (EG) compared to the active control group (CG) [mean difference (95% confidence interval) between EG and CG: -0.034 [-0.062, -0.007], P = .012], with a small-to-moderate effect size (partial η 2  = 0.055)., Conclusions and Implications: This is the first study to show that a 12-week exergame intervention reduces the level of frailty in people with dementia. This is an important and promising result, because frailty is a powerful predictor for adverse health outcomes, and its reduction may have positive effects on health status. Moreover, exergaming resulted in high adherence rates of physical exercise, which makes it an effective strategy to engage people with dementia in physical activity., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Introduction/purpose: Little is known about the comparative effectiveness of exercise programs, especially when delivered at a high intensity, in mobility-limited older adults. We compared the effects of 25 sessions of high-intensity agility exergaming (EXE) and stationary cycling (CYC) at the same cardiovascular load on measured and perceived mobility limitations, balance, and health-related quality of life in mobility-limited older adults., Methods: Randomized to EXE (n = 28) and CYC (n = 27), mobility-impaired older adults (age 70 yr) exercised five times per week for 5 wk at 80% of age-predicted maximal heart rate. Waitlisted controls did not exercise (n = 28)., Results: Groups did not differ at baseline in any outcomes (P > 0.05). The primary outcomes (The Short Form-36-Health Survey: EXE, 6.9%; effect size, 2.2; CYC, 5.5%, 1.94; Western Ontario and McMaster Universities Osteoarthritis Index: EXE, -27.2%, -3.83; CYC, -17.2, -2.90) improved similarly (P > 0.05). Secondary outcomes, including body mass (-3.7%), depression (-18%), and walking capacity (13.5%) also improved (P < 0.05) similarly after the two interventions. Activities of daily living, Berg Balance Score, BestTest scores, and Dynamic Gait Index improved more (P < 0.05) after EXE than CYC. Center of pressure of standing sway path improved in one of six tests only after EXE (P < 0.05). Postexercise cardiovascular response improved in EXE (P = 0.019). CON did not change in any outcomes (P > 0.05)., Conclusions: When matched for cardiovascular and perceived effort, two diverse high-intensity exercise programs improved health-related quality of life, perceived mobility limitation, and walking capacity similarly and balance outcomes more in mobility-limited older adults, expanding these older adults' evidence-based exercise options to reduce mobility limitations.

This systematic review and meta-analysis examined the dose-response relationship between exercise and cognitive function in older adults with and without cognitive impairments. We included single-modality randomized controlled aerobic, anaerobic, multicomponent or psychomotor exercise trials that quantified training frequency, session and program duration and specified intensity quantitatively or qualitatively. We defined total exercise duration in minutes as the product of program duration, session duration, and frequency. For each study, we grouped test-specific Hedges' d (n = 163) and Cohen's d (n = 23) effect sizes in the domains Global cognition, Executive function and Memory. We used multilevel mixed-effects models to investigate dose-related predictors of exercise effects. In healthy older adults (n = 23 studies), there was a small positive effect of exercise on executive function (d = 0.27) and memory (d = 0.24), but dose-parameters did not predict the magnitude of effect sizes. In older adults with cognitive impairments (n = 13 studies), exercise had a moderate positive effect on global cognition (d = 0.37). For older adults with cognitive impairments, we found evidence for exercise programs with a short session duration and high frequency to predict higher effect sizes (d = 0.43-0.50). In healthy older adults, dose-parameters did not predict the magnitude of exercise effects on cognition. For older adults with cognitive impairments, exercise programs with shorter session duration and higher frequency may generate the best cognitive results. Studies are needed in which different exercise doses are directly compared among randomized subjects or conditions., Competing Interests: The authors have declared that no competing interests exist.

Background: There is a poor understanding of the dose-response relationship between years of physical activity and motor and cognitive function. We determined the dose-response effects of physical activity duration in years on motor and cognitive function and their relationship in healthy old females., Objectives: To determine the dose-effects of physical activity duration in years on motor and cognitive function and their relationship in health aging adults., Methods: We conducted a retrospective observational study with 201 old (age 69 years; SD=5.9) and 12 young (mean age 21 years; SD=1.9) females, with sub-groups based on number of years of self-reported physical activity. Aerobic capacity, mobility, functional reach, standing balance, global cognition, episodic memory, executive function, and processing speed were assessed with performance-based tests. We analyzed sub-group differences quantitatively and qualitatively and performed regression and mediation analyses to determine predictors and mediators of physical activity effects., Results: Based on physical activity of minimal (0.3 y, n=29), short (2.4 y, n=77), moderate (6.2 y, n=36) and long (16.6 y, n=59) duration, physical activity for at least 2.4 years affords old adults benefits in body mass index with peak dose-effects present in aerobic capacity and mobility at 6.2 years without additional benefits after 16.6 years of physical activity. Physical activity for any duration had no effects on functional reach, balance, executive function, episodic memory, and processing speed. Although weakly mobility predicted global cognition and executive function., Conclusion: Performing physical activity up to 6.2 years on average had favorable effects on body mass index, aerobic capacity and mobility. The data strengthen current recommendations for an active lifestyle in adulthood to prevent aging-related motor and cognitive decline., (Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background/aims: Reliable and valid neuropsychological tests for patients with dementia are scarce. To improve the assessment of attention and inhibitory control in dementia, we determined the feasibility, test-retest reliability, and validity of a Flanker task., Methods: Participants with all-cause diagnosed dementia ( n = 22, mean age 84 years; mean Mini-Mental State Examination [MMSE] score = 19.4) performed a computerized Flanker task twice within 7 days. The Flanker task required participants to indicate the direction of target arrows flanked by congruent or incongruent arrows. Number of completed trials, accuracy, and reaction times (RTs) were recorded, and interference scores were calculated from basic scores. We examined the psychometric properties of the Flanker task and its relationship with the MMSE and Stroop test., Results: The Flanker task was feasible. Test-retest reliability was good for number of correct answers and RTs, and fair to poor for accuracy and the interference scores. The correlation of the Flanker task with Stroop and MMSE performance was fair to poor., Conclusion: The Flanker task appears to be feasible, and a reliable and valid measure of selective attention. Although the test-retest reliability for the Flanker RT interference measure was fair, future studies need to confirm its validity to measure inhibitory control in patients with dementia.

Purpose: The Drug Burden Index (DBI) is a tool to quantify the anticholinergic and sedative load of drugs. Establishing functional correlates of the DBI could optimize drug prescribing in patients with dementia. In this cross-sectional study, we determined the relationship between DBI and cognitive and physical functions in a sample of patients with dementia., Methods: Using performance-based tests, we measured physical and cognitive functions in 140 nursing home patients aged over 70 with all-cause dementia. We also determined anticholinergic DBI (AChDBI) and sedative DBI (SDBI) separately and in combination as total drug burden (TDB)., Results: Nearly one half of patients (48%) used at least one DBI-contributing drug. In 33% of the patients, drug burden was moderate (0 < TDB < 1) whereas in 15%, drug burden was high (TDB ≥ 1). Multivariate models yielded no associations between TDB, AChDBI, and SDBI, and physical or cognitive function (all p > 0.05)., Conclusions: A lack of association between drug burden and physical or cognitive function in this sample of patients with dementia could imply that drug prescribing is more optimal for patients with dementia compared with healthy older populations. However, such an interpretation of the data warrants scrutiny as several dementia-related factors may confound the results of the study.