Search

Objectives:Disinhibited behaviors in dementia are associated with multiple negative outcomes. However, effective interventions are under-researched. This systematic review aims to provide an overview of intervention studies that report outcome measures of disinhibited behaviors in dementia.Design:Systematic searches of the databases MEDLINE, EMBASE, and PsychINFO, Social Work Abstracts and Cochrane Central Register of Controlled Trial databases were conducted for publications published between 2002 and March 2020. We included hand-searched reviews, original articles, case reports, cohort studies, and randomized controlled trials (RCTs). All studies were rated for research quality. Statistical and clinical significance were considered for individual studies. Effect sizes were included where provided or calculated where possible. Mean effect sizes were calculated for RCTs only.Participants:The systematic review included studies involving people living with dementia.Measurements:The Neuropsychiatric Inventory disinhibition subscale was used most often.Results:Nine pharmacological and 21 nonpharmacological intervention studies utilized different theoretical/clinical approaches. These included pain management, antidepressants, models of care, education and/or training, music-based approaches, and physical activity. The quality of research in RCTs was strong with a greater effect size in nonpharmacological compared to pharmacological approaches (mean Cohen’s d = 0.49 and 0.27, respectively). Disinhibition was a secondary outcome in all studies.Conclusion:Pharmacological (including pain management and antidepressants) and, more so, nonpharmacological (models of care, education/training, physical activity, and music) approaches were effective in reducing disinhibition.

NEW FINDINGS What is the central question of this study? Cerebrovascular reactivity (CVR) is a common functional test to assess brain health, and impaired CVR has been associated with all-cause cardiovascular mortality: does the duration of the CO2 stimulus and the time point used for data extraction alter the CVR outcome measure? What is the main finding and its importance? This study demonstrated CVR measures calculated from 1 and 2 min CO2 stimulus durations were significantly higher than CVR calculated from a 4 min CO2 stimulus. CVRs calculated from the first 2 min of the CO2 stimulus were significantly higher than CVR values calculated from the final minute if the duration was ≥4 min. This study highlights the need for consistent methodological approaches. ABSTRACT Cerebrovascular reactivity to carbon dioxide (CVR) is a common functional test to assess brain vascular health, though conflicting age and fitness effects have been reported. Studies have used different CO2 stimulus durations to induce CVR and extracted data from different time points for analysis. Therefore, this study examined whether these differences alter CVR and explain conflicting findings. Eighteen healthy volunteers (24 ± 5 years) inhaled CO2 for four stimulus durations (1, 2, 4 and 5 min) of 5% CO2 (in air) via the open-circuit Douglas bag method, in a randomized order. CVR data were derived from transcranial Doppler (TCD) measures of middle cerebral artery blood velocity (MCAv), with concurrent ventilatory sensitivity to the CO2 stimulus ( VE,CO2 ). Repeated measures ANOVAs compared CVR and VE,CO2 measures between stimulus durations and steady-state time points. An effect of stimulus duration was observed (P = 0.002, η² = 0.140), with 1 min (P = 0.010) and 2 min (P

Cerebral blood flow (CBF) measures are used in clinical settings to diagnose conditions (e.g., vasospasms, sickle cell disease, stroke, dementia, confirmation of brain death), as well as in research, emerging as potential early biomarkers of declining brain health. The aim of this chapter is to provide an overview of approaches used to measure CBF for determining resting cerebral tissue perfusion and functional CBF responsiveness. We will highlight the strengths and weaknesses of each and illustrate the methodological differences that need to be considered when assessing brain vascular health. The imaging methods measuring CBF will cover: Doppler ultrasound (spanning transcranial Doppler (TCD), duplex ultrasound, and transcranial color Doppler (TCCD)), magnetic resonance imaging (MRI) (including arterial spin labeling (ASL), blood oxygenation level dependent (BOLD) signal measures and phase-contrast angiography), and finally near-infrared spectroscopy (NIRS).

Depression is a common psychological symptom associated with dementia. Pharmacological approaches are often used despite two large negative trials of efficacy. This meta-analysis examines nonpharmacological (i.e., psychosocial) approaches for symptoms of depression in people living with dementia and reports statistical and clinical significance.Relevant studies published between 2012 and 2020 were sourced by searching electronic databases: MEDLINE, EMBASE, PsychINFO, Social Work Abstracts and the Cochrane Central Register of Controlled Trials. Studies were assessed for methodological quality. Random-effects meta-analysis was performed to calculate a pooled effect size (ES) and 95% confidence intervals (CI).Overall, 37 nonpharmacological studies were identified including 2,636 participants. The mean quality rating was high (12/14, SD=1.4). Meta-analysis revealed that nonpharmacological approaches were significantly associated with reduced symptoms of depression with a medium effect size (ES=-0.53, 95%CI [-0.72, -0.33], p 0.0001). There was considerable heterogeneity between studies. Meta-regression revealed this was not driven by intervention type or setting (residential versus community).Nonpharmacological approaches such as reminiscence, cognitive stimulation/ rehabilitation, therapeutic, music-based approaches and education/ training, have the potential to reduce symptoms of depression in dementia.

Introduction Resting cerebral blood flow (CBF) and perfusion measures have been used to determine brain health. Studies showing variation in resting CBF with age and fitness level using different imaging approaches have produced mixed findings. We assess the degree to which resting CBF measures through transcranial Doppler (TCD) and arterial spin labeling (ASL) MRI provide complementary information in older and younger, fit and unfit cohorts. Methods Thirty‐five healthy volunteers (20 younger: 24 ± 7y; 15 older: 66 ± 7y) completed two experimental sessions (TCD/MRI). Aging and fitness effects within and between imaging modalities were assessed. Results Middle cerebral artery blood velocity (MCAv, TCD) was lower and transit time (MRI) slower in older compared with younger participants (p, We assess the degree to which resting CBF measures from transcranial Doppler (TCD) and arterial spin labeling (ASL) MRI provide complementary information in older and younger, fit and unfit cohorts. Middle cerebral artery blood velocity (MCAv, TCD) was lower and transit time (MRI) slower in older compared with younger participants, though fitness effects in the younger group opposed those in the older group. Whole cohort transit times correlated with MCAv, whereas tissue perfusion did not correlate with TCD measures.

Cocoa flavanols protect humans against vascular disease, as evidenced by improvements in peripheral endothelial function, likely through nitric oxide signalling. Emerging evidence also suggests that flavanol-rich diets protect against cognitive aging, but mechanisms remain elusive. In a randomized double-blind within-subject acute study in healthy young adults, we link these two lines of research by showing, for the first time, that flavanol intake leads to faster and greater brain oxygenation responses to hypercapnia, as well as higher performance only when cognitive demand is high. Individual difference analyses further show that participants who benefit from flavanols intake during hypercapnia are also those who do so in the cognitive challenge. These data support the hypothesis that similar vascular mechanisms underlie both the peripheral and cerebral effects of flavanols. They further show the importance of studies combining physiological and graded cognitive challenges in young adults to investigate the actions of dietary flavanols on brain function.

The optimal exercise intensity and modality for maximizing cerebral blood flow (CBF) and hence potential exposure to positive, hemodynamically derived cerebral adaptations is yet to be fully determined. This study compared CBF velocity responses between running and cycling across a range of exercise intensities. Twenty‐six participants (12 females; age: 26 ± 8 years) completed four exercise sessions; two mode‐specific maximal oxygen consumption (VO2max) tests, followed by (order randomized) two incremental exercise protocols (3‐min stages at 35%, 50%, 65%, 80%, 95% VO2max). Continuous measures of middle cerebral artery velocity (MCAv), oxygen consumption, end‐tidal CO2 (PETCO2), and heart rate were obtained. Modality‐specific MCAv changes were observed for the whole group (interaction effect: p = .01). Exercise‐induced increases in MCAvmean during cycling followed an inverted‐U pattern, peaking at 65% VO2max (Δ12 ± 7 cm/s from rest), whereas MCAvmean during running increased linearly up to 95% VO2max (change from rest: Δ12 ± 13 vs. Δ7 ± 8 cm/s for running vs. cycling at 95% VO2max; p = .01). In contrast, both modalities had an inverted‐U pattern for PETCO2 changes, although peaked at different intensities (running: 50% VO2max, Δ6 ± 2 mmHg; cycling: 65% VO2max, Δ7 ± 2 mmHg; interaction effect: p = .01). Further subgroup analysis revealed that the running‐specific linear MCAvmean response was fitness dependent (Fitness*modality*intensity interaction effect: p = .04). Above 65% VO2max, fitter participants (n = 16; male > 45 mL/min/kg and female > 40 mL/min/kg) increased MCAvmean up to 95% VO2max, whereas in unfit participants (n = 7, male, This study compared cerebral blood flow (CBF) responses between running and cycling across a range of exercise intensities. Our findings demonstrate that exercise‐induced increases in CBF (as indexed from Doppler‐based measures of middle cerebral artery velocity, MCAv) during incremental running and cycling differ at higher exercise intensities, with the pattern of the MCAv response during running for fitter individuals dissociating from the regulatory influence of PCO2 at near maximal intensity (95% VO2max). Thus, modality‐specific differences in beat‐to‐beat flow patterns may alter CBF regulation processes and affect the complex integration of factors regulating CBF during exercise.

SUMMARYNAD+ is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+ levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.

What is the topic of this review? The topic of this review is to consider innovative exercise strategies that optimize neuroprotection in order to combat cognitive decline and neurodegenerative disease in older age. What advances does it highlight? The review summarizes current understanding around exercise mode, duration, frequency and intensity, and then highlights adaptive roles of select stressors that have equal if not indeed greater capacity than exercise per se to induce health-related adaptation in the brain. These stressors include, but are not exclusively limited to, hydrostatic and thermal stress, hypoxia, nutritional supplementation and cognitive loading, and are effective by targeting specific pathways that collectively contribute towards improved brain structure and function. The prevalence of cognitive decline and neurodegenerative diseases (e.g. stroke and dementia) is increasing. Numerous studies show that regular exercise has beneficial effects on brain health in clinical and non-clinical populations, yet adherence to public health exercise guidelines is notoriously poor. Recently, novel exercise strategies have been investigated to allow for more individualized and prescriptive approaches that target the key mechanistic pathways that allow exercise to mediate adaptation. This work exploring alternative approaches to the traditional model of exercise training has demonstrated exciting potential for positive health-related adaptations (especially for metabolic, muscle and cardiovascular function). However, few studies to date have focused on brain adaptations. The aim of this review is to summarize new and innovative interventions that have the potential to optimize exercise for improved brain health (i.e. brain structure and function). First, we briefly summarize current understanding of the nature whereby positive effects of exercise deliver their influence on the brain (i.e. underlying mechanisms and factors affecting its delivery). Second, we introduce the effects of exercise training on cognition and give examples of studies showing the beneficial effects of exercise in clinical populations. Finally, we explore the adaptive roles of individual stressors that may induce greater health-related adaptations in the brain than exercise alone, including environmental stressors (hydrostatic stress, thermal stress and hypoxia), nutritional supplementation and cognitive loading. In summary, optimized interventions that target key mechanistic pathways linked to improved brain structure and function could ultimately protect against and/or ameliorate cognitive decline and neurodegenerative diseases.

Summary Nicotinamide adenine dinucleotide (NAD+) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR., Graphical Abstract, Highlights • NR supplementation in aged subjects augments the skeletal muscle NAD+ metabolome • NR supplementation does not affect skeletal muscle mitochondrial bioenergetics • NR supplementation reduces levels of circulating inflammatory cytokines, Elhassan et al. show that oral nicotinamide riboside increases the NAD+ metabolome in aged human skeletal muscle, without apparently altering mitochondrial bioenergetics. Measures of muscle and whole-body metabolism are also unchanged. Nicotinamide riboside reduces the levels of circulating inflammatory cytokines. Studies in relevant human disease models are warranted.

Healthy ageing is associated with decline in cognitive abilities such as language. Aerobic fitness has been shown to ameliorate decline in some cognitive domains, but the potential benefits for language have not been examined. In a cross-sectional sample, we investigated the relationship between aerobic fitness and tip-of-the-tongue states. These are among the most frequent cognitive failures in healthy older adults and occur when a speaker knows a word but is unable to produce it. We found that healthy older adults indeed experience more tip-of-the-tongue states than young adults. Importantly, higher aerobic fitness levels decrease the probability of experiencing tip-of-the-tongue states in healthy older adults. Fitness-related differences in word finding abilities are observed over and above effects of age. This is the first demonstration of a link between aerobic fitness and language functioning in healthy older adults ispartof: Scientific Reports vol:8 issue:1 ispartof: location:England status: Published online

Summary: Nicotinamide adenine dinucleotide (NAD+) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR. : Elhassan et al. show that oral nicotinamide riboside increases the NAD+ metabolome in aged human skeletal muscle, without apparently altering mitochondrial bioenergetics. Measures of muscle and whole-body metabolism are also unchanged. Nicotinamide riboside reduces the levels of circulating inflammatory cytokines. Studies in relevant human disease models are warranted. Keywords: nicotinamide adenine dinucleotide, metabolism, aging, inflammation, cell adhesion

What is the topic of this review? The topic of this review is to consider innovative exercise strategies that optimize neuroprotection in order to combat cognitive decline and neurodegenerative disease in older age. What advances does it highlight? The review summarizes current understanding around exercise mode, duration, frequency and intensity, and then highlights adaptive roles of select stressors that have equal if not indeed greater capacity than exercise per se to induce health-related adaptation in the brain. These stressors include, but are not exclusively limited to, hydrostatic and thermal stress, hypoxia, nutritional supplementation and cognitive loading, and are effective by targeting specific pathways that collectively contribute towards improved brain structure and function. The prevalence of cognitive decline and neurodegenerative diseases (e.g. stroke and dementia) is increasing. Numerous studies show that regular exercise has beneficial effects on brain health in clinical and non-clinical populations, yet adherence to public health exercise guidelines is notoriously poor. Recently, novel exercise strategies have been investigated to allow for more individualized and prescriptive approaches that target the key mechanistic pathways that allow exercise to mediate adaptation. This work exploring alternative approaches to the traditional model of exercise training has demonstrated exciting potential for positive health-related adaptations (especially for metabolic, muscle and cardiovascular function). However, few studies to date have focused on brain adaptations. The aim of this review is to summarize new and innovative interventions that have the potential to optimize exercise for improved brain health (i.e. brain structure and function). First, we briefly summarize current understanding of the nature whereby positive effects of exercise deliver their influence on the brain (i.e. underlying mechanisms and factors affecting its delivery). Second, we introduce the effects of exercise training on cognition and give examples of studies showing the beneficial effects of exercise in clinical populations. Finally, we explore the adaptive roles of individual stressors that may induce greater health-related adaptations in the brain than exercise alone, including environmental stressors (hydrostatic stress, thermal stress and hypoxia), nutritional supplementation and cognitive loading. In summary, optimized interventions that target key mechanistic pathways linked to improved brain structure and function could ultimately protect against and/or ameliorate cognitive decline and neurodegenerative diseases.

The ability to monitor one's sleepiness has obvious implications for safety critical procedures. Laboratory findings indicate that we may be poor at doing this compared with objective measurements (e.g. reaction times (RT)). However, the respective testing situations usually differ, to favour objective measures. These typically entail longer test durations with less distractions; both factors facilitate sleepiness. Using the Karolinska Sleepiness Scale (KSS) we compared subjective responses with RTs, in 2 min epochs, over 10 min periods in identical quiet settings, early afternoon, in 21 healthy volunteers with 5h prior night's sleep restriction. Whereas the initial KSS score was unrelated to 10 min RT, the KSS subsequently showed a similar, significant increase, comparable with RT. Changes in both scores were very significantly correlated. KSS scores indicated that 5 min was an effective 'settling down' period. Participants were good at estimating their sleepiness if presented with a procedure equivalent to that of the objective measure.