IMPACT

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Protein IMPACT (Imprinted and ancient gene protein homolog)

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Load-dependent modulation of alpha oscillations during working memory encoding and retention in young and older adults.

Working memory (WM) is vulnerable to age-related decline, particularly under high loads. Visual alpha oscillations contribute to WM performance in younger adults, and although alpha decreases in power and frequency with age, it is unclear if alpha activity supports WM in older adults. We recorded electroencephalography (EEG) while 24 younger (aged 18-35 years) and 30 older (aged 50-86) adults performed a modified Sternberg task with varying load conditions. Older adults demonstrated slower reaction times at all loads, but there were no significant age differences in WM capacity. Regardless of age, alpha power decreased and alpha frequency increased with load during encoding, and the magnitude of alpha suppression during retention was larger at higher loads. While alpha power during retention was lower than fixation in older, but not younger adults, the relative change from fixation was not significantly different between age groups. Individual differences in alpha power did not predict performance for either age groups or at any WM loads. We demonstrate that alpha power and frequency are modulated in a similar task- and load-dependent manner during WM in both older and younger adults when WM performance is comparable across age groups. IMPACT STATEMENT: Aging is associated with a marked decrease in the power and frequency of alpha oscillations. Here, we demonstrate that when verbal working memory performance is matched across age groups, alpha power and frequency are modulated in a similar task- and load-dependent manner in both young and older adults.


Keywords

  • EEG
  • alpha oscillations
  • cognitive aging
  • working memory


Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis of the IMPACT Trial.

In the IMPACT trial, single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations, with a similar safety profile. Research Question Does age have an effect on trial outcomes? IMPACT was a Phase III, double-blind, 52-week trial. Patients ≥40 years of age with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 mcg, FF/VI 100/25 mcg, or UMEC/VI 62.5/25 mcg. Endpoints assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough forced expiratory volume in 1 second (FEV ), proportion of St George's Respiratory Questionnaire (SGRQ) responders (≥4 units decrease from baseline in SGRQ total score) and safety. The intent-to-treat population comprised 10,355 patients; 4724 (46%), 4225 (41%), and 1406 (14%) were ≤64, 65-74, and ≥75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates versus FF/VI (% reduction [95% confidence interval (CI)], ≤64 years: 8% [-1, 16], p=0.070; 65-74 years: 22% [14, 29], p<0.001; ≥75 years 18% [3, 31], p=0.021) and versus UMEC/VI (≤64 years: 16% [7, 25], p=0.002; 65-74 years: 33% [25, 41], p<0.001; ≥75 years 24% [6, 38], p=0.012), with greatest rate reduction seen in the 65-74 and ≥75 years subgroups. Post hoc analyses of CFB in trough FEV , and proportion of SGRQ responders at Week 52 were significantly greater with FF/UMEC/VI than FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status versus FF/VI and UMEC/VI irrespective of age for most endpoints, with a similar safety profile. GSK (CTT116855/NCT02164513).


Keywords

  • COPD
  • aging
  • exacerbations
  • safety
  • single-inhaler triple therapy


Using Video Telehealth to Deliver Patient-Centered Collaborative Care: The G-IMPACT Pilot.
This pilot project aimed to explore a new model of healthcare delivery to older adult medically complex Veterans by combining telehealth technology with an interdisciplinary medical team operating in real time. : The Geriatric-Interdisciplinary Mobile Patient Access Team (G-IMPACT) was comprised of a field team including a nurse practitioner and technology assistant who visited enrolled patients in their homes using synchronous video to link to a suite of geriatric specialists in a video-enabled room at a Veterans Affairs hospital. Clinicians interacted with patients, caregivers, and each other to develop mutually agreed upon treatment plans that were then immediately implemented in the field. : 11 total visits were conducted with 9 Veteran patients aged 55-91 (mean = 75.3 years). Both patients and clinicians reported a high level of satisfaction across multiple metrics, including visit quality, and positive indirect indicators of effectiveness were apparent from qualitative data. : Nurse practitioner facilitated video visits allowed geriatric patients to meet with multiple specialists simultaneously with both high patient satisfaction and increased real-time care coordination. : This project identified challenges and opportunities afforded by this type of real-time telehealth care delivery and can inform the development of future interdisciplinary mobile medical teams.


Keywords

  • Telehealth
  • aging
  • care coordination
  • home care
  • interdisciplinary
  • medicine
  • older adult
  • video


AGING, HEART RATE VARIABILITY AND METABOLIC IMPACT OF OBESITY.

The relationship between aging and changes in heart rate variability (HRV) could depend on the metabolic profile of obese people, i.e. metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). We aimed to determine the age at which obesity related autonomic dysfunction becomes significant and whether it decreases differently according to metabolic profile. We analyzed HRV in 99 adults using Wildman's criteria for metabolic profile and 5-minute HRV for autonomic nervous system. In MHO, high frequency (HF) decreased in the 4 decade of life. In MUO, standard deviation of R-R intervals (SDNN), root mean square of successive differences of all R-R intervals (RMSSD), number of adjacent intervals differing by more than 50 ms expressed as percentage of all intervals in the collecting period (pNN50), HF, low frequency (LF), LF/HF (LF divided by HF) and total power (TP) decreased in the 4 decade of life (partial shared variance 28%-36%). In conclusion, an age dependent decrease of HRV occurs in MUO between the third and fifth decade of life. In MHO, HF significantly decreases around the age of 40 years. Cardiometabolic profile influences metabolic aging, altering the autonomic nervous system.

MeSH Terms

  • Aging
  • Autonomic Nervous System
  • Autonomic Nervous System Diseases
  • Female
  • Heart Rate
  • Humans
  • Male
  • Metabolic Diseases
  • Metabolism
  • Middle Aged
  • Obesity

Keywords

  • Aging
  • Autonomic nervous system
  • Heart rate
  • Obesity, metabolically benign
  • Parasympathetic nervous system
  • Sympathetic nervous system


Endophytic Bacillus strains isolated from alfalfa (Medicago sativa L.) seeds: enhancing the lifespan of Caenorhabditis elegans.

Medicago sativa L. (alfalfa) is an important forage crop throughout the world. Despite the abiotic nutritional components of alfalfa having been extensively studied, there is only limited information on alfalfa endophytes. In this study, thirteen endophytic bacteria were isolated from alfalfa seeds. Bacillus (76·9%) was the most abundant genus, followed by Enterobacter (15·4%), Brevibacterium (7·7%), Geobacillus (7·7%) and Staphylococcus (7·7%). Four of the 13 endophytic bacteria, including Bacillus amyloliquefaciens EnB-alf1, Bacillus subtilis EnB-alf3, EnB-alf5 and EnB-alf13, were capable of significantly extending the lifespan of Caenorhabditis elegans. In addition, B. amyloliquefaciens EnB-alf1 enhanced the resistance of C. elegans to thermal stress whereas B. subtilis EnB-alf3 enhanced the resistance to oxidative stress. Further studies demonstrated that the enhanced lifespan of the worm was depended on the function of DAF-2/DAF-16 and was associated with the colonization of strain in the worms' intestines when strain EnB-alf1 or strain EnB-alf3 was presented to the worms as food sources. Our results suggest that some endophytic Bacillus strains isolated from alfalfa are beneficial on C. elegans health. SIGNIFICANCE AND IMPACT OF THE STUDY: Medicago sativa L. (alfalfa) is an important forage crop throughout the world. Despite the abiotic nutritional components of alfalfa having been extensively studied, there is only limited information available on alfalfa endophytes. Beneficial bacteria residing in the host intestine have been shown to affect host longevity. However, there is limited information available on the functions of alfalfa seed endophytes to nematodes. In this study, four endophytic Bacillus strains isolated from alfalfa seeds were found to significantly extend the lifespan of Caenorhabditis elegans and enhance resistance to thermal and oxidative stress. Our results suggest that some endophytic Bacillus strains isolated from alfalfa seeds can promote good health in C. elegans.

MeSH Terms

  • Animals
  • Bacillus subtilis
  • Brevibacterium
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Endophytes
  • Enterobacter
  • Forkhead Transcription Factors
  • Geobacillus
  • Longevity
  • Medicago sativa
  • Oxidative Stress
  • Receptor, Insulin
  • Seeds
  • Staphylococcus

Keywords

Caenorhabditis elegans

  • alfalfa seeds
  • bacterial endophytes
  • isolation
  • longevity


Temporal trend in dementia incidence since 2002 and projections for prevalence in England and Wales to 2040: modelling study.

 To forecast dementia prevalence with a dynamic modelling approach that integrates calendar trends in dementia incidence with those for mortality and cardiovascular disease.  Modelling study.  General adult population of England and Wales.  The English Longitudinal Study of Ageing (ELSA) is a representative panel study with six waves of data across 2002-13. Men and women aged 50 or more years, selected randomly, and their cohabiting partners were recruited to the first wave of ELSA (2002-03). 11392 adults participated (response rate 67%). To maintain representativeness, refreshment participants were recruited to the study at subsequent waves. The total analytical sample constituted 17 906 people. Constant objective criteria based on cognitive and functional impairment were used to ascertain dementia cases at each wave.  To estimate calendar trends in dementia incidence, correcting for bias due to loss to follow-up of study participants, a joint model of longitudinal and time-to-event data was fitted to ELSA data. To forecast future dementia prevalence, the probabilistic Markov model IMPACT-BAM (IMPACT-Better Ageing Model) was developed. IMPACT-BAM models transitions of the population aged 35 or more years through states of cardiovascular disease, cognitive and functional impairment, and dementia, to death. It enables prediction of dementia prevalence while accounting for the growing pool of susceptible people as a result of increased life expectancy and the competing effects due to changes in mortality, and incidence of cardiovascular disease.  In ELSA, dementia incidence was estimated at 14.3 per 1000 person years in men and 17.0/1000 person years in women aged 50 or more in 2010. Dementia incidence declined at a relative rate of 2.7% (95% confidence interval 2.4% to 2.9%) for each year during 2002-13. Using IMPACT-BAM, we estimated there were approximately 767 000 (95% uncertainty interval 735 000 to 797 000) people with dementia in England and Wales in 2016. Despite the decrease in incidence and age specific prevalence, the number of people with dementia is projected to increase to 872 000, 1 092 000, and 1 205 000 in 2020, 2030, and 2040, respectively. A sensitivity analysis without the incidence decline gave a much larger projected growth, of more than 1.9 million people with dementia in 2040.  Age specific dementia incidence is declining. The number of people with dementia in England and Wales is likely to increase by 57% from 2016 to 2040. This increase is mainly driven by improved life expectancy.

MeSH Terms

  • Aged
  • Dementia
  • England
  • Female
  • Health Surveys
  • Humans
  • Incidence
  • Life Expectancy
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Models, Theoretical
  • Population Surveillance
  • Prevalence
  • Sex Distribution
  • Socioeconomic Factors
  • Time Factors
  • Wales


[How do general practitioners evaluate collaborative care of elderly depressed patients? Results of a qualitative study].

Depression is a very common disease among the elderly. Various studies demonstrated the need to improve the care for elderly depressed patients. Within the GermanIMPACT trial specifically trained care managers were engaged to cooperate with general practitioners (GPs). This study investigates how GPs evaluate this cooperation and their attitude towards collaborative care. To explore the perspective of GPs a qualitative study design with semi-structured interviews was chosen. The guideline-based interviews were conducted with GPs from the intervention group, the control group and with GPs who had decided not to participate in the trial. The interviews were audio-taped, fully transcribed and analysed. Eighteen GPs were interviewed. Almost all GPs from the intervention group appreciated the support by care managers. Advantages they mentioned included their own relief by the committed conversation between patient and care manager, the continuous monitoring of the patients as well as the regular feedback via protocols. GPs who refused to take part in the study expressed different attitudes towards collaborative care. Due to the general overall positive valuation of care managers as well as their positive attitude towards collaborative care a continuation of the IMPACT program in Germany should be considered. More investigation needs to be done to answer the question how care managers can be integrated in everyday primary care.

MeSH Terms

  • Aged
  • Aging
  • Attitude of Health Personnel
  • Cooperative Behavior
  • Depressive Disorder
  • General Practitioners
  • Germany
  • Humans
  • Interprofessional Relations
  • Primary Health Care
  • Qualitative Research

Keywords

  • Altersdepression
  • Koordinierte Versorgung
  • Qualitative Methoden
  • collaborative care
  • hausärztliche Versorgung
  • late-life depression
  • primary care
  • qualitative methods


Assessment of frailty in aged dogs.

OBJECTIVE To define a frailty-related phenotype-a clinical syndrome associated with the aging process in humans-in aged dogs and to investigate its association with time to death. ANIMALS 116 aged guide dogs. PROCEDURES Dogs underwent a clinical geriatric assessment (CGA) and were followed to either time of death or the study cutoff date. A 5-component clinical definition of a frailty phenotype was derived from clinical items included in a geriatric health evaluation scoresheet completed by veterinarians during the CGA. Univariate (via Kaplan-Meier curves) and multivariate (via Cox proportional hazards models) survival analyses were used to investigate associations of the 5 CGA components with time to death. RESULTS 76 dogs died, and the median time from CGA to death was 4.4 years. Independent of age at the time of CGA, dogs that had ≥ 2 of the 5 components (n = 10) were more likely to die during the follow-up period, compared with those that had 1 or no components (adjusted hazard ratio, 3.9 [95% confidence interval, 1.4 to 10.9]). After further adjustments for subclinical or clinical diseases and routine biomarkers, the adjusted hazard ratio remained significant. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that signs of frailty appeared to be a risk factor for death in dogs. The concept of frailty in dogs requires further development. IMPACT FOR HUMAN MEDICINE The concept of frailty, as defined for humans, seems transposable to dogs. Given that they share humans' environments and develop several age-related diseases similar to those in humans, dogs may be useful for the study of environmental or age-related risk factors for frailty in humans.

MeSH Terms

  • Aging
  • Animals
  • Cadaver
  • Dogs
  • Female
  • Male
  • Physical Fitness
  • Proportional Hazards Models


IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans.

The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2. Here, we tested whether IMPACT down-regulation mimics the effects of DR in C. elegans. Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2-dependent manner. Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi. IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR.

MeSH Terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Protein Kinase Inhibitors
  • Protein Kinases
  • RNA Interference
  • Signal Transduction
  • Transcription Factors

Keywords

  • Aging
  • Dietary restriction
  • GCN2
  • IMPACT
  • Integrated stress response


[SPECULAR MICROSCOPY NORMATIVE DATA: DOES PATIENT AGE HAVE AN IMPACT ON CORNEAL ENDOTHELIUM FEATURES IN ELDERLY EYES?].

Corneal endothelium is essential for adequate corneal hydration and transparency. Age and ethnicity- related variability in endothelial properties is known. To determine specular microscopy trends in the elderly and to provide normative data of endothelial features of the sampled cohort of the Israeli population aged 55-88 years. This is a retrospective cross-sectional study analyzing specular microscopy data of the Israeli population aged 55-88 years and the determination of correlation of age to specular microscopy features. A comparison of endothelial properties was conducted between age-based groups: 55-64 years, 65-74 years, and 75-88 years. One hundred and eighty eight eyes of 188 patients, mean age 71.05 ± 7.9 years, were included; Mean Cell Density 2549.53 ± 294.71 cells/mm²; Coefficient of variation (CV) 42.12 ± 6.9%; Hexagonality (Hexa) 49.15 ± 6.62%; Central Corneal thickness (CCT) 552 ± 47 µm. A weak correlation was observed between cell density and age [r = -0.169; p = 0.02); CV, Hexa, and CCT did not show any correlation with age. Group analysis did not reveal statistically significant differences between the following age groups: 55-64 years; 65-74 years; 75-88 years Normative data of endothelial properties of the sampled cohort of Israeli population aged 55-88 years is provided. Age has a weak correlation with cell density. Considering the aging of the population, endothelial properties do not justify the rejection of potential donors based on age alone.

MeSH Terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • Cell Count
  • Cellular Senescence
  • Cornea
  • Cross-Sectional Studies
  • Endothelium, Corneal
  • Female
  • Humans
  • Israel
  • Male
  • Microscopy
  • Middle Aged
  • Normal Distribution
  • Statistics as Topic


THE IMPACT OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS ON THE CAPTIVE ASIAN ELEPHANT (ELEPHAS MAXIMUS) POPULATION OF THE UNITED KINGDOM AND IRELAND (1995-2013).

Elephant endotheliotropic herpesvirus (EEHV) is one of the most devastating infections and causes of mortality in captive Asian elephant ( Elephas maximus ) populations. Eight confirmed fatal EEHV cases have occurred since 1995 within the captive Asian elephant population of the United Kingdom and Ireland. This report aims to review the impact of EEHV on the captive Asian elephant population in the United Kingdom and Ireland, document and compare fatal cases, and recommend a framework of monitoring within the United Kingdom and Ireland to increase the success of treatment of EEHV hemorrhagic disease (EEHV HD) in the future. Six zoologic institutions (which include zoos, safari parks, and wildlife parks) that currently house or have previously housed a captive Asian elephant group were included in this report. Medical records and postmortem results were collected from four of these institutions for each confirmed fatal case. EEHV HD was found to be responsible for 29.6% of fatalities in Asian elephants born in captivity in the United Kingdom and Ireland between 1995 and 2013. Following a review of all the cases, it is shown that although clinical signs may be associated with specific EEHV species, the swiftness of disease progression means that most body tissues are impacted 1-6 days following the presentation of visible clinical signs and treatment is less likely to succeed. Therefore, EEHV monitoring should consist of conducting regular polymerase chain reaction analysis of whole blood samples from at-risk, young Asian elephants aged 1-8 yr in order for subclinical viremia to be identified early and treatment to be started before the appearance of visible clinical signs.

MeSH Terms

  • Aging
  • Animals
  • Elephants
  • Female
  • Herpesviridae
  • Herpesviridae Infections
  • Ireland
  • Male
  • United Kingdom

Keywords

  • Case studies
  • EEHV
  • elephant calves
  • health monitoring
  • hemorrhagic disease


THE IMPACT OF LATE-LIFE ANXIETY AND DEPRESSION ON COGNITIVE FLEXIBILITY AND COGNITIVE RESTRUCTURING SKILL ACQUISITION.

Studies examining treatment moderators and mediators in late-life anxiety and depression are sparse. Executive functioning skills decrease with age, and are poorer in the context of anxiety and depression. One of the key cognitive behavioral therapy techniques for anxiety and depression is cognitive restructuring (CR), which teaches people to identify and dispute maladaptive thoughts. There is evidence that cognitive flexibility (CF), one aspect of executive functioning, has a negative impact on CR skill acquisition in nonclinical older adults, and this warrants extension in a clinical sample. This study assessed CR skill acquisition in a clinical sample of 47 older adults with anxiety and depression and 53 nonclinical controls during an experimental paradigm, and investigated the influence of CF on this relationship. A battery of neuropsychological tests assessing CF were administered and CR was learned during a brief intervention. The clinical sample showed poorer CF on some measures, as well as poorer CR quality and efficacy (reduction in subjective distress). CF partially mediated the relationship between clinical status and CR quality, and between clinical status and CR efficacy. These results provide preliminary evidence that older adults with anxiety and depression are worse at learning and benefiting from CR with a brief intervention and this is partially due to having poorer CF skills. These findings warrant further examination in a treatment context to assess whether CR skill acquisition improves over treatment.

MeSH Terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Anxiety
  • Cognition
  • Cognitive Behavioral Therapy
  • Depression
  • Executive Function
  • Female
  • Humans
  • Male
  • Neuropsychological Tests
  • Thinking

Keywords

  • aging
  • cognitive restructuring
  • cognitive therapy
  • executive function


Group-mediated physical activity promotion and mobility in sedentary patients with knee osteoarthritis: results from the IMPACT-pilot trial.

To compare the effects of a group-mediated cognitive behavioral exercise intervention (GMCB) with traditional center-based exercise therapy (TRAD) on objectively assessed levels of physical activity (PA) and mobility in sedentary patients with knee osteoarthritis (OA). The Improving Maintenance of Physical Activity in Knee Osteoarthritis Trial-Pilot (IMPACT-P) was a 12-month, 2-arm, single-blind, randomized controlled pilot study designed to compare the effects of GMCB and TRAD on 80 sedentary patients with knee OA with self-reported difficulty in daily activities [mean age 63.5 yrs, 84% women, mean body mass index (BMI) 32.7 kg/m(2)]. Objective assessments of PA (LIFECORDER Plus Accelerometer) and mobility (400-m walk) were obtained at baseline, 3 months, and 12 months by study personnel blinded to participants' treatment assignment. Intent to treat 2 (treatment: GMCB and TRAD) × 2 (time: 3 mos and 12 mos) analyses of covariance of controlling for baseline, age, sex, and BMI-adjusted change in the outcomes demonstrated that the GMCB intervention yielded significantly greater increases in PA (p < 0.01) and a nonsignificant yet more favorable improvement in mobility (p = 0.09) relative to TRAD. Partial correlation analyses also revealed that change in PA was significantly correlated with the 400-m walk performance at 3-month (r = -0.51, p < 0.01) and 12-month (r = -0.40, p < 0.01) followup assessments. Findings from the IMPACT-P trial suggest that the GMCB treatment resulted in significantly greater improvement in PA and nonsignificant yet more favorable change in mobility relative to TRAD.

MeSH Terms

  • Aged
  • Body Mass Index
  • Exercise Therapy
  • Female
  • Health Promotion
  • Humans
  • Male
  • Middle Aged
  • Motor Activity
  • Osteoarthritis, Knee
  • Pilot Projects
  • Single-Blind Method
  • Treatment Outcome
  • Walking

Keywords

  • AGING
  • EXERCISE
  • MOBILITY
  • OSTEOARTHRITIS
  • PHYSICAL ACTIVITY