Addressing the challenge to identify the role played by lifestyle factors in dementia.
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ABSTRACT:
SUBMITTER: Akbaraly T
PROVIDER: S-EPMC7327356 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Addressing the challenge to identify the role played by lifestyle factors in dementia.
Annals of translational medicine 20200601 11
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Project description:IntroductionWe first examined the role of age at cardiovascular disease (CVD) onset for incident dementia, and then examined whether lifestyle factors at guideline-recommended levels in individuals with CVD mitigates dementia risk.MethodsWe used population-based data (Whitehall II: n = 10,308/baseline 1985-1988/examinations every 4-5 years). Lifestyle factors (non-smoking, body mass index [BMI], physical activity, diet) were extracted post-CVD.ResultsOver a median of 31.6 years, 3275 (32.1%) developed CVD. At age 70, risk of dementia was higher in individuals with CVD onset before (hazard ratio [HR] of incident dementia for participants with CVD before age 60, using participants without CVD at age 70 as the reference: 1.56, 95% confidence interal [CI] 1.18-2.08) but not after 60 years. In participants with CVD, a greater number of lifestyle factors at recommended levels post-CVD was associated with a lower dementia risk (per lifestyle factor at recommended level HR: 0.73, 95% CI 0.59-0.92).DiscussionOur results suggest that early onset CVD is associated with a higher dementia risk at older ages. In those with CVD, the dementia risk was lower if lifestyle factors are at recommended levels following CVD diagnosis.HighlightsCVD in midlife but not in late life is associated with a higher risk of dementia. Dementia risk in CVD patients is lower if their lifestyle factors are at recommended levels. These findings provide evidence to promote CVD prevention in midlife or earlier. Study findings also show the importance of a healthy lifestyle in those with CVD.
| S-EPMC10947967 | biostudies-literature
Project description:BACKGROUND:The role of lifestyle factors and sleep for dementia is uncertain. OBJECTIVE:To examine the associations of major lifestyle factors and sleep duration with risk of late-onset dementia. METHODS:We used data from a population-based cohort of 28,775 Swedish adults who were ?65 years of age and completed a questionnaire about lifestyle and other modifiable factors in the autumn of 1997. Dementia cases were ascertained by linkage with the Swedish National Patient Register. RESULTS:During a mean follow-up of 12.6 years, dementia was diagnosed among 3,755 participants (mean age at diagnosis 83.2±5.1 years). There were no associations of an overall healthy diet (defined by a modified Dietary Approaches to Stop Hypertension Diet score or a Mediterranean diet score), alcohol and coffee consumption, or physical activity with dementia incidence. Compared with never smokers, dementia risk was increased in former and current smokers (hazard ratio [95% confidence interval] = 1.13 [1.04-1.23] and 1.10 [1.00-1.21], respectively). Extended time of sleep (>9 h per night) was associated with an increased risk of dementia. However, this association appeared to be related to a reverse causation effect since the association did not remain after exclusion of cases diagnosed within the first five or ten years of follow-up. CONCLUSIONS:This study found no evidence that major lifestyle factors, aside from smoking, or sleep duration influence the risk of dementia.
| S-EPMC6218132 | biostudies-literature
Project description:BackgroundArachidonic acid (AA) is oxidized by cytochrome P450s (CYPs) to form epoxyeicosatrienoic acids (EETs), compounds that modulate ion transport, gene expression, and vasorelaxation. Both CYP2Cs and CYP2Js are involved in kidney EET epoxidation.MethodsIn this study, we used a CYP2C11-null rat model to explore the in vivo effects of CYP2C11 on vasorelaxation. For 2 months, CYP2C11-null and wild-type (WT) Sprague-Dawley rats were either fed normal lab (0.3% (w/w) sodium chloride) or high-salt (8% (w/w) sodium chloride) diets. Subsequently, an invasive method was used to determine blood pressure. Next, western blots, quantitative PCR, and immunohistochemistry were used to determine renal expression of CYPs involved in AA metabolism.ResultsAmong CYP2C11-null rats, a high-salt diet (females: 156.79 ± 15.89 mm Hg, males: 130.25 ± 16.76 mm Hg, n = 10) resulted in significantly higher blood pressure than a normal diet (females: 118.05 ± 8.43 mm Hg, P < 0.01; males: 115.15 ± 11.45 mm Hg, P < 0.05, n = 10). Compared with WT rats under the high-salt diet, western blots showed that CYP2C11-null rats had higher renal expression of CYP2J2 and CYP4A. This was consistent with the results of immunohistochemistry and the qPCR, respectively. The two rat strains did not differ in the renal expression of CYP2C23 or CYP2C24.ConclusionOur findings suggested that CYP2C11 plays an important role in lowering blood pressure under the challenge of a high-salt diet.
| S-EPMC6485204 | biostudies-literature
Project description:ImportanceElite-level contact sport participation is associated with increased dementia risk, which may be attributable to sport-related traumatic brain injury and repetitive head impact exposure. However, the contribution of wider, potentially modifiable dementia risk factors remains uncertain.ObjectiveTo explore the association of potentially modifiable dementia risk factors with dementia risk among former professional soccer players.Design, setting, and participantsThis retrospective cohort study used electronic health record linkage to national electronic datasets of general and mental health hospital inpatient and day-case admissions, prescribing information, and death certification in Scotland for male former professional soccer players born between January 1, 1900, and December 31, 1990, who were aged 30 years or older on December 31, 2020, and general population control individuals matched by sex, year of birth, and area socioeconomic status. Database interrogation was performed on November 30, 2021, and data were analyzed between January 16, 2023, and July 8, 2024.ExposuresHistory of smoking, depression, alcohol-related disorders, diabetes, hypertension, hearing loss, and obesity coded within electronic health records.Main outcomes and measuresPrevalence of dementia risk factors and their association with incident dementia diagnoses were evaluated and compared between former soccer players and matched controls.ResultsThe final cohort consisted of 11 984 male former professional soccer players and 35 952 matched controls. Over a median 21 years (IQR, 7-34 years) of follow-up from study entry at age 30 years or older, providing a total of 1 039 848 years of follow-up, 434 former soccer players (3.62%) and 453 matched population controls (1.26%) were identified with a dementia diagnosis (hazard ratio [HR], 3.02; 95% CI, 2.54-3.58; P < .001). Overall, rates of general health and lifestyle dementia risk factors were similar or lower among former soccer players compared with matched controls (eg, diabetes: 4.26% vs 6.35%). Dementia risk associated with these factors among soccer players was similar to or lower than among controls (eg, hypertension: HR, 4.62 [95% CI, 3.69-5.78] vs 6.96 [95% CI, 5.64-8.59]).Conclusions and relevanceThis cohort study found no evidence that high dementia risk among former professional soccer players was associated with potentially modifiable general health and lifestyle dementia risk factors. These data support continuation of measures directed toward reducing exposure to repetitive head impacts and traumatic brain injury in sport.
| S-EPMC11629125 | biostudies-literature
Project description:The purpose of this manuscript is to provide, based on an extensive analysis of a proteomic data set, suggestions for proper statistical analysis for the discovery of sets of clinically relevant biomarkers. As tractable example we define the measurable proteomic differences between apparently healthy adult males and females. We choose urine as body-fluid of interest and CE-MS, a thoroughly validated platform technology, allowing for routine analysis of a large number of samples. The second urine of the morning was collected from apparently healthy male and female volunteers (aged 21-40) in the course of the routine medical check-up before recruitment at the Hannover Medical School.We found that the Wilcoxon-test is best suited for the definition of potential biomarkers. Adjustment for multiple testing is necessary. Sample size estimation can be performed based on a small number of observations via resampling from pilot data. Machine learning algorithms appear ideally suited to generate classifiers. Assessment of any results in an independent test-set is essential.Valid proteomic biomarkers for diagnosis and prognosis only can be defined by applying proper statistical data mining procedures. In particular, a justification of the sample size should be part of the study design.
| S-EPMC3017845 | biostudies-other
Project description:Extensive literature in the United States documents racial/ethnic and gender disparities in the incidence and prevalence of dementia yet few studies have examined how race/ethnicity and gender intersect to shape inequalities in the risk of dementia. Moreover, few studies have examined heterogeneity in the contribution of known risk factors to dementia across these demographic strata while properly accounting for the semi-competing risk of death. I calculated the proportion of dementia cases attributable to socioeconomic, lifestyle, and medical risk factors across demographic subgroups using nationally representative data from the US-based Health and Retirement Study for the years 2000-2016 and a multistate framework that accounts for the semi-competing risk of death. Socioeconomic resources contributed to the largest number of dementia cases but the magnitude of this contribution varied across strata defined by race/ethnicity and gender. The greatest potential for dementia prevention was observed among non-Hispanic black and Hispanic men and women, supporting an intersectionality approach, and underscoring the need for culturally sensitive intervention and public health initiatives to address the growing burden of dementia. Taken together, work demonstrates the potential benefit of taking an intersectional approach to understanding disparities in dementia.
| S-EPMC8683757 | biostudies-literature
Project description:ObjectivesThis study aimed to conduct a feasibility pilot of the Dementia Lifestyle Coach program; an individual coaching and counselling program for people recently diagnosed with dementia, to help them to adjust to the diagnosis and live well.MethodsA randomised controlled pilot trial (n = 11) with wait-list control group was undertaken over 12 months. Intervention group participants received immediate personalised counselling from a registered psychologist and monthly support (face-to-face or by telephone) from a trained peer mentor living with dementia. The wait-listed control group commenced treatment 6 months after baseline.ResultsRecruitment and delivery of the Dementia Lifestyle Coach program was highly feasible. The program was acceptable, with nine of the 11 participants describing benefits including informational and emotional support, improving their outlook and mood, and family relationships. The planned program was adapted to participants' individual needs.ConclusionsThis small pilot showed that it is feasible to recruit for and deliver a counselling and peer mentoring program for people recently diagnosed with dementia. A larger hybrid implementation randomised control trial should be conducted to evaluate efficacy and effectiveness.
| S-EPMC10946602 | biostudies-literature
Project description:BackgroundThere is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria.MethodCross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ? 30 kg/m(2)) and non-obese (BMI < 30 kg/m(2)). Metabolic health status was defined using five existing MH definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined.ResultsThe prevalence of MHO varied considerably between definitions (2.2% to 11.9%), was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006).ConclusionA standard MHO definition is required. Moderate and high levels of physical activity and compliance with food pyramid recommendations increase the likelihood of MHO. Stratification of obese individuals based on their metabolic health phenotype may be important in ascertaining the appropriate therapeutic or intervention strategy.
| S-EPMC3798285 | biostudies-literature
Project description:BackgroundMultidomain trials to prevent dementia by simultaneously targeting multiple risk factors with non-pharmacological lifestyle interventions show promise. Designing trials to evaluate the efficacy of individual interventions and their combinations is methodologically challenging. Determining the efficacy is, nevertheless, important to individuals, payers, and for resource allocations to support intervention implementation.Main bodyThe central rationale for seminal trials improving cardiovascular health or reducing falls risk in older adults is that multifactorial conditions may be amenable to improvement by simultaneously targeting multiple modifiable risk factors. Similar reasoning underlies lifestyle interventions to reduce dementia risk using combinations of physical exercise, cognitive training, diet, amelioration of vascular-metabolic risk factors, and improving sleep quality. Randomizing individuals with at least two modifiable risk factors to "standardly tailored" interventions to mitigate their risk factors, versus a comparator arm, will yield an unbiased estimate of the cumulative average effect of modifying more versus fewer risk factors. The between-group difference in the cognitive primary outcome will reflect both the main effects of the mitigated risk factors, as well as their synergistic effects. However, given the positive trial results, there are inherent challenges in quantifying post hoc which components, or combination of components, were responsible for improvements in cognition. Here, we elaborate on these methodological challenges and important considerations in using a standardly tailored design with two arms (one consisting of multidomain interventions tailored to participants' risk profiles and another consisting of active control conditions). We compare this approach to fully factorial designs and highlight the disadvantages and advantages of each. We discuss partial solutions, including analytical strategies such as risk reduction scores that measure reductions in the number or severity of risk factors in each study arm. Positive results can support the causal inference that between-group differences in the primary cognitive outcome were due to risk factor modification.ConclusionStandardly tailored designs are pragmatic and feasible evaluations of multidomain interventions to reduce dementia risk. We propose sensitivity and exploratory analyses of between-group reductions in the severity of risk factors, as a methodology to bolster causal inferences that between-group differences in the primary cognitive outcome are due to the risk factors modified.
| S-EPMC9275261 | biostudies-literature
Project description:Staphylococcus epidermidis is a ubiquitous human commensal skin bacterium that is also one of the most prevalent nosocomial pathogens. The genetic factors underlying this remarkable lifestyle plasticity are incompletely understood, mainly due to the difficulties of genetic manipulation, precluding high-throughput functional profiling of this species. To probe the versatility of S. epidermidis to survive across a diversity of environmental conditions, we developed a large-scale CRISPR interference (CRISPRi) screen complemented by transcriptional profiling (RNA sequencing) across 24 diverse conditions and piloted a droplet-based CRISPRi approach to enhance throughput and sensitivity. We identified putative essential genes, importantly revealing amino acid metabolism as crucial to survival across diverse environments, and demonstrated the importance of trace metal uptake for survival under multiple stress conditions. We identified pathways significantly enriched and repressed across our range of stress and nutrient-limited conditions, demonstrating the considerable plasticity of S. epidermidis in responding to environmental stressors. Additionally, we postulate a mechanism by which nitrogen metabolism is linked to lifestyle versatility in response to hyperosmotic challenges, such as those encountered on human skin. Finally, we examined the survival of S. epidermidis under acid stress and hypothesize a role for cell wall modification as a vital component of the survival response under acidic conditions. Taken together, this study integrates large-scale CRISPRi and transcriptomics data across multiple environments to provide insights into a keystone member of the human skin microbiome. Our results additionally provide a valuable benchmarking analysis for CRISPRi screens and are a rich resource for other staphylococcal researchers. IMPORTANCE Staphylococcus epidermidis is a bacteria that broadly inhabits healthy human skin, yet it is also a common cause of skin infections and bloodstream infections associated with implanted medical devices. Because human skin has many different types of S. epidermidis, each containing different genes, our goal is to determine how these different genes allow S. epidermidis to switch from healthy growth in the skin to being an infectious pathogen. Understanding this switch is critical to developing new strategies to prevent and treat S. epidermidis infections.
| S-EPMC9765180 | biostudies-literature