Association between APOE Genotype and Change in Physical Function in a Population-Based Swedish Cohort of Older Individuals Followed Over Four Years.
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ABSTRACT:
SUBMITTER: Skoog I
PROVIDER: S-EPMC5047916 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dupuytren's disease (DD) is a fibroproliferative disorder affecting the palmar fascia of the hand. Risk factors include diabetes mellitus (DM), whereas a high body mass index (BMI) is associated with a lower prevalence of DD. The aim of this study was to further elucidate risk and protective factors for the development of DD using longitudinal population-based data from the Malmö Diet and Cancer Study (MDCS). During 1991-1996, the inhabitants aged 46-73 years in the city of Malmö, Sweden were invited to participate in the population-based MDCS (41% participation rate). Data on incident DD were retrieved from Swedish national registers. Associations between DM, alcohol consumption, BMI, and serum apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) at baseline were analysed in multivariable Cox regression models adjusted for known confounders. Among 30,446 recruited participants, 347 men and 194 women were diagnosed with DD during a median follow-up time of 23 years. DM (men HR 2.23; 95% CI 1.50-3.30, women HR 2.69; 95% CI 1.48-4.90) and alcohol consumption (men HR 2.46; 95% CI 1.85-3.27, women HR 3.56; 95% CI 1.95-6.50) were independently associated with incident DD in the Cox regression models. Furthermore, inverse associations with incident DD were found for obesity among men, and ApoB/ApoA1 ratio among both sexes. DM and excess alcohol consumption constituted major risk factors for the development of DD. Furthermore, an inverse association between obesity among men and DD, and also between ApoB/ApoA1 ratio and DD was found in both sexes.
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Project description:ObjectivesCognitive dysfunction is a key feature of bipolar disorder (BD). However, not much is known about its temporal stability, as some studies have demonstrated a neurodegenerative model in BD while others have shown no change in cognitive functioning over time. Building upon our prior work, which examined the natural course of executive functioning, the current study aimed to investigate the natural course of memory, emotion processing, and fine motor dexterity over a 5-year period in BD and healthy control (HC) samples.MethodsUsing a 5-year longitudinal cohort, 90 individuals with BD and 17 HCs were administered a battery of neuropsychological tests at study baseline and at 1 and 5 years after study entry that captured four areas of cognitive performance: visual memory, auditory memory, emotion processing, and fine motor dexterity.ResultsLatent growth curve modeling showed no group differences in the slopes of any of the cognitive factors between the BD and HC groups. Age at baseline was negatively associated with visual memory, emotion processing, and fine motor dexterity. Education level was positively associated with auditory and visual memory and fine motor. Female gender was negatively associated with emotion processing.ConclusionsExtending our prior work on longitudinal evaluation of executive functioning, individuals with BD show similar linear change in other areas of cognitive functioning including memory, emotion processing, and fine motor dexterity as compared to unaffected HCs. Age, education, and gender may have some differential effects on cognitive changes.
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Project description:Introduction: Physical activity (PA) is inversely associated with risk of heart failure and cardiovascular disease (CVD), whereas increased left ventricular (LV) mass and mass to volume (m:v) ratio are unfavorable CVD risk factors. We assessed whether changes in leisure time PA were associated with longitudinal changes in cardiac structure in a community-based population.Methods: We included 2779 Multi-Ethnic Study of Atherosclerosis participants, free of baseline CVD, who had available data on PA and cardiac magnetic resonance imaging at examinations 1 (2000-2002) and 5 (2010-2012). Physical activity was measured by a Typical Week PA Survey and converted to MET-minutes per week of moderate+vigorous activity. We used linear mixed effect models to estimate the associations of baseline and change in PA with baseline and change in cardiac structure, adjusting for CVD risk factors and body size.Results: At baseline, the mean age was 59 yr, 53% were women, and 58% of nonwhite race/ethnicity. During average 10-yr follow-up, and after accounting for baseline PA levels, the highest quintiles of PA increase were significantly associated with increases in LV mass (2.3 g; 95% confidence interval [CI], 0.4-4.2), LV end-diastolic volume (4.7 mL; 95% CI, 2.4-7.0), and stroke volume (3.3 mL; 95% CI, 1.6-5.1), but lower M:V ratio (-2.9; 95% CI, -5.0 to -0.8) compared with the lowest quintiles. Increasing exercise PA was associated with increases in LV diameter and reductions in M:V ratio, whereas occupational PA was associated with increases in m:v ratio. Increasing PA over 10 yr was also associated with greater risk of eccentric dilated LV hypertrophy at examination 5.Conclusions: After accounting for baseline PA, greater positive changes in leisure-time PA levels were associated with a more eccentric-type of LV remodeling pattern over 10 yr. The clinical implications of such findings remain to be determined.
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Project description:ObjectiveQuadriceps weakness, associated with functional limitations, is a target of treatment of knee osteoarthritis (OA). Limited data exist on the relationship between modest strength increases and improvements in function. The aim of this study was to evaluate concurrent change in strength and physical function over 5 years.MethodsAmong subjects from the Multicenter Osteoarthritis (MOST) study, we excluded those with knee replacement after baseline. A 3-category variable defined whether, at 5 years, knee extensor strength increased, decreased, or remained within 15% of baseline, a clinically important cut-off. The outcomes were the 5-times sit-to-stand test, 20-meter walk test, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) physical function score, and 3 individual physical functions from WOMAC: arising from a chair, going up stairs, and getting on/off toilet. Linear and logistic models, stratified by sex, evaluated associations between change in strength and change in physical function over 5 years. To compare weaker versus stronger women, we stratified analyses at 56 Nm baseline strength.ResultsAmong 1,534 participants (60.6% women), 22% of men and 30% of women increased strength by at least 15% at 5 years. Compared with women whose strength did not change, women whose strength increased had improved chair stand performance (odds ratio 2.27 [95% confidence interval 1.56, 3.30]) but no improvement in other functions. In men, an increase in strength was not associated with significant improvement in physical function. Similar results were observed for a 20% or 30% increase.ConclusionModest improvement in quadriceps strength was associated with improved chair stand performance in women but not in men. Most functions did not improve with an increase in strength, and targeted interventions may be required to improve functional status.
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Project description:Little is known about the evolution of protein structures and the degree of protein structure conservation over planetary time scales. Here, we report the X-ray crystal structures of seven laboratory resurrections of Precambrian thioredoxins dating up to approximately four billion years ago. Despite considerable sequence differences compared with extant enzymes, the ancestral proteins display the canonical thioredoxin fold, whereas only small structural changes have occurred over four billion years. This remarkable degree of structure conservation since a time near the last common ancestor of life supports a punctuated-equilibrium model of structure evolution in which the generation of new folds occurs over comparatively short periods and is followed by long periods of structural stasis.
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Project description:We investigated the influence of the apolipoprotein E-ɛ4 allele (APOE-ɛ4) on longitudinal age-related changes in brain functional connectivity (FC) and cognition, in view of mixed cross-sectional findings. One hundred and twenty-two healthy older adults (aged 58-79; 25 APOE-ɛ4 carriers) underwent task-free fMRI scans at baseline. Seventy-eight (16 carriers) had at least one follow-up (every 2 years). Changes in intra- and internetwork FCs among the default mode (DMN), executive control (ECN), and salience (SN) networks, as well as cognition, were quantified using linear mixed models. Cross-sectionally, APOE-ɛ4 carriers had lower functional connectivity between the ECN and SN than noncarriers. Carriers also showed a stronger age-dependent decrease in visuospatial memory performance. Longitudinally, carriers had steeper increase in inter-ECN-DMN FC, indicating loss of functional segregation. The longitudinal change in processing speed performance was not moderated by APOE-ɛ4 genotype, but the brain-cognition association was. In younger elderly, faster loss of segregation was correlated with greater decline in processing speed regardless of genotype. In older elderly, such relation remained for noncarriers but reversed for carriers. APOE-ɛ4 may alter aging by accelerating the change in segregation between high-level cognitive systems. Its modulation on the longitudinal brain-cognition relationship was age-dependent.
| S-EPMC6866329 | biostudies-literature
Project description:BACKGROUND:Cognitive training may contribute to the ability to maintain cognitive function in healthy elderly adults. Whether genotype modifies training effects remains unknown. OBJECTIVE:Assess influence of APOE on cognitive function over time in community-dwelling elderly adults participating in multi-domain cognitive training. METHODS:Healthy individuals ?70 years of age were screened from one urban community in Shanghai. 145 healthy Chinese older adults met inclusion criteria and were assigned to intervention (n?=?88) or control (n?=?57) groups. Multi-domain cognitive training involved 24 sessions of different content taking place over 12 weeks. Neuropsychological testing was administered at baseline, immediately after training, six months and twelve months post-intervention; composite measures of cognitive function were identified via factor analysis. RESULTS:Three factors explained the majority of variance in function (verbal memory, processing speed, executive function). The intervention attenuated 12-month declines in processing speed, regardless of APOE genotype (p?=?0.047). Executive function declined in APOE?4 carriers over 12 months, regardless of intervention (p?=?0.056). There was a significant interaction after 12 months where intervention ?4 carriers had better processing speed than ?4 controls (p?=?0.003). Intervention ?2 carriers had better executive function immediately after training (p?=?0.02) and had better verbal memory 6-months post-intervention (p?=?0.04). These effects remained significant after false-discovery rate correction. CONCLUSION:Multi-domain cognitive training reduces declines in processing speed over time. APOE?4 is associated with reductions in executive function over time, and training may attenuate ?4-associated declines in processing speed. APOE?2 carriers may also benefit from training, particularly on measures of executive function and verbal memory.
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Project description:BackgroundImplementation science frameworks aided the development of a new, evidence-based clinical physical therapy program. The purpose of this report is to describe the process of sustaining a clinical program in practice for over 4 years. We present a framework for integrating tools for sustainability with the Knowledge-to-Action model in the context of a proactive physical therapy (PAPT) program for individuals with early-stage Parkinson's disease.MethodsSustainability of implementation strategies was addressed using the Dynamic Sustainability Framework and sustainability assessment tools. Repeated retrospective medical record reviews and phone interviews were used to evaluate the reach and adoption of the PAPT over 4 years. Characteristics of those who engaged with PAPT, implementation fidelity, and clinical effectiveness were assessed for year 1 and year 3. Sustainability was measured using RE-AIM, NHS Sustainability Model, and Clinical Sustainability Assessment Tool.ResultsReach increased from 28 to 110 total patients per year and spread occurred from one to three sites. PAPT user age, sex, Hoehn and Yahr rating, time since diagnosis, and type of insurance were similar in year 1 and year 3 (p > 0.05). The program sustained its effect to help participants increase or maintain self-reported exercise (Y1, 95%; Y3, 100%). However, upon evaluation PAPT users in year 3 had longer time since symptom onset and worse UPDRS motor scores compared to the PAPT users in year 1 (p < 0.05). All sites sustained the core intervention components, with sustainability scores of 71/100 (± 9.9) on the NHS Sustainability Model and 6.1/7 (± 0.9) on the Clinical Sustainability Assessment Tool.ConclusionsIntegrating multiple sustainability models and assessments supported continued effectiveness, spread, and sustainment of PAPT for 4 years. Effective planning, anticipating common healthcare changes, and addressing sustainability determinants early in program implementation were essential aspects of long-term success.
| S-EPMC8477476 | biostudies-literature
Project description:BackgroundFor adults in general population community settings, data regarding long-term course and outcomes of illicit drug use are sparse, limiting the formulation of evidence-based recommendations for drug use screening of adults in primary care.ObjectiveTo describe trajectories of three illicit drugs (cocaine, opioids, amphetamines) among adults in community settings, and to assess their relation to all-cause mortality.DesignLongitudinal cohort, 1987/88-2005/06.SettingCommunity-based recruitment from four cities (Birmingham, Chicago, Oakland, Minneapolis).ParticipantsHealthy adults, balanced for race (black and white) and gender were assessed for drug use from 1987/88-2005/06, and for mortality through 12/31/2008 (n = 4301)MeasurementsUse of cocaine, amphetamines, and opioids (last 30 days) was queried in the following years: 1987/88, 1990/91, 1992/93, 1995/96, 2000/01, 2005/06. Survey-based assessment of demographics and psychosocial characteristics. Mortality over 18 years.ResultsTrajectory analysis identified four groups: Nonusers (n = 3691, 85.8%), Early Occasional Users (n = 340, 7.9%), Persistent Occasional Users (n = 160, 3.7%), and Early Frequent/Later Occasional Users (n = 110, 2.6%). Trajectories conformed to expected patterns regarding demographics, other substance use, family background and education. Adjusting for demographics, baseline health status, health behaviors (alcohol, tobacco), and psychosocial characteristics, Early Frequent/Later Occasional Users had greater all-cause mortality (Hazard Ratio, HR = 4.94, 95% CI = 1.58-15.51, p = 0.006).LimitationsStudy is restricted to three common drugs, and trajectory analyses represent statistical approximations rather than identifiable "types". Causal inferences are tentative.ConclusionsFour trajectories describe illicit drug use from young adulthood to middle age. Two trajectories, representing over one third of adult users, continued use into middle age. These persons were more likely to continue harmful risk behaviors such as smoking, and more likely to die.
| S-EPMC3378735 | biostudies-literature
Project description:The high physical activity/high aerobic fitness phenotype predicts low morbidity and mortality more strongly than any other known biological risk factor. Inherited and/or acquired properties of skeletal muscle seem to be linked with aerobic fitness and other cardio-metabolic risk factors3. However, physical activity-induced changes in muscle and fat tissue-related complex molecular networks and their links with cardio-metabolic disease risk are not comprehensively understood. Here we show that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in musculus vastus lateralis tissue samples is chronically up-regulated for the central pathways or genes related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. In addition to aerobic fitness, upregulation of these pathways is associated in particular with high HDL cholesterol levels. In fat tissue we found physical activity-induced increases in polyunsaturated fatty acid metabolism and in branched chain amino acid degradation, which increases were associated with decreased ‘high-risk’ ectopic body fat and low glucose levels. Consistent with other findings plasma lipidomics analyses showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. The findings indicate the main pathways in skeletal muscle and fat tissue that mediate the chronic effects of physical activity on reduced cardio-metabolic disease risk, including the increase in aerobic fitness. Up-regulation of oxidative energy metabolism seems to be a common underlying mechanism.
2010-07-31 | GSE20319 | GEO