Functional connectivity among brain regions affected in Alzheimer's disease is associated with CSF TNF-α in APOE4 carriers.

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.

Exergaming as a Physical Exercise Strategy Reduces Frailty in People With Dementia: A Randomized Controlled Trial.

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 η2 = 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.

Diverse Exercises Similarly Reduce Older Adults' Mobility Limitations.

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.

Dose-response relationship between exercise and cognitive function in older adults with and without cognitive impairment: A systematic review and meta-analysis.

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.

Psychometric Properties of a Flanker Task in a Sample of Patients with Dementia: A Pilot Study.

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.