Associations between sex, systemic iron and inflammatory status and subcortical brain iron.

Brain iron increases in several neurodegenerative diseases are associated with disease progression. However, the causes of increased brain iron remain unclear. This study investigates relationships between subcortical iron, systemic iron and inflammatory status. Brain magnetic resonance imaging (MRI) scans and blood plasma samples were collected from cognitively healthy females (n = 176, mean age = 61.4 ± 4.5 years, age range = 28-72 years) and males (n = 152, mean age = 62.0 ± 5.1 years, age range = 32-74 years). Regional brain iron was quantified using quantitative susceptibility mapping. To assess systemic iron, haematocrit, ferritin and soluble transferrin receptor were measured, and total body iron index was calculated. To assess systemic inflammation, C-reactive protein (CRP), neutrophil:lymphocyte ratio (NLR), macrophage colony-stimulating factor 1 (MCSF), interleukin 6 (IL6) and interleukin 1ß (IL1ß) were measured. We demonstrated that iron levels in the right hippocampus were higher in males compared with females, while iron in the right caudate was higher in females compared with males. There were no significant associations observed between subcortical iron levels and blood markers of iron and inflammatory status indicating that such blood measures are not markers of brain iron. These results suggest that brain iron may be regulated independently of blood iron and so directly targeting global iron change in the treatment of neurodegenerative disease may have differential impacts on blood and brain iron.

Accelerating glacier volume loss on Juneau Icefield driven by hypsometry and melt-accelerating feedbacks.

Globally, glaciers and icefields contribute significantly to sea level rise. Here we show that ice loss from Juneau Icefield, a plateau icefield in Alaska, accelerated after 2005 AD. Rates of area shrinkage were 5 times faster from 2015-2019 than from 1979-1990. Glacier volume loss remained fairly consistent (0.65-1.01 km3 a-1) from 1770-1979 AD, rising to 3.08-3.72 km3 a-1 from 1979-2010, and then doubling after 2010 AD, reaching 5.91 ± 0.80 km3 a-1 (2010-2020). Thinning has become pervasive across the icefield plateau since 2005, accompanied by glacier recession and fragmentation. Rising equilibrium line altitudes and increasing ablation across the plateau has driven a series of hypsometrically controlled melt-accelerating feedbacks and resulted in the observed acceleration in mass loss. As glacier thinning on the plateau continues, a mass balance-elevation feedback is likely to inhibit future glacier regrowth, potentially pushing glaciers beyond a dynamic tipping point.

Active Compared With Passive Voiding Trials After Midurethral Sling Surgery: A Systematic Review.

OBJECTIVE: To compare active with passive voiding trials on the rate of passing a trial of void and discharge rates with catheter in women who have undergone midurethral sling for treatment of stress urinary incontinence (SUI). DATA SOURCES: MEDLINE, EMBASE, and ClinicalTrials.gov were searched through February 24, 2023. METHODS OF STUDY SELECTION: Our population included women undergoing midurethral sling, with or without anterior or posterior repair, for treatment of SUI. Our two primary outcomes were rate of passing voiding trial and rate of discharge with a catheter. Our secondary outcome was the rate of delayed postoperative urinary retention, when a patient initially passes a trial of void but then subsequently presents in retention. TABULATION, INTEGRATION, AND RESULTS: Abstracts were doubly screened; full-text articles were doubly screened; and accepted articles were doubly extracted. In single-arm studies evaluating either passive or active voiding trial, random-effects meta-analyses of pooled proportions were used to assess outcomes. Of 3,033 abstracts screened, 238 full-text articles were assessed, and 26 met inclusion criteria. Ten studies including 1,370 patients reported active trial of void. Sixteen studies including 3,643 patients reported passive trial of void. We included five randomized controlled trials, five comparative retrospective studies, five prospective single group studies, and 11 retrospective single group studies. Five of the studies included patients with a concomitant anterior or posterior colporrhaphy. On proportional meta-analysis, the active trial of void group was less likely to pass the voiding trial (81.0%, 95% CI, 0.76-0.87% vs 89.0%, 95% CI, 0.84-0.9%3, P =.029) with high heterogeneity ( I2 =93.0%). Furthermore, there were more discharges with catheter in active trial of void compared with passive trial of void (19.0%, 95% CI, 0.14-0.24% vs 7.0%, 95% CI, 0.05-0.10%, P <.01). The rates of delayed postoperative urinary retention were low and not different between groups (0.6%, 95% CI, 0.00-0.02% vs 0.2%, 95% CI, 0.00-0.01%, P =.366) with low heterogeneity ( I2 =0%). Sling revisions were statistically lower in the active trial of void group (0.5%, 95% CI, 0.00-0.01% vs 1.5%, 95% CI, 0.01-0.02%, P =.035) with low heterogeneity ( I2 =10.4%). CONCLUSION: Passive trial of void had higher passing rates and lower discharge with catheter than active trial of void. Rates of most complications were low and similar between both groups, although passive trial of void had higher sling revisions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022341318.

Disrupted limbic-prefrontal effective connectivity in response to fearful faces in lifetime depression.

BACKGROUND: Multiple brain imaging studies of negative emotional bias in major depressive disorder (MDD) have used images of fearful facial expressions and focused on the amygdala and the prefrontal cortex. The results have, however, been inconsistent, potentially due to small sample sizes (typically N<50). It remains unclear if any alterations are a characteristic of current depression or of past experience of depression, and whether there are MDD-related changes in effective connectivity between the two brain regions. METHODS: Activations and effective connectivity between the amygdala and dorsolateral prefrontal cortex (DLPFC) in response to fearful face stimuli were studied in a large population-based sample from Generation Scotland. Participants either had no history of MDD (N=664 in activation analyses, N=474 in connectivity analyses) or had a diagnosis of MDD during their lifetime (LMDD, N=290 in activation analyses, N=214 in connectivity analyses). The within-scanner task involved implicit facial emotion processing of neutral and fearful faces. RESULTS: Compared to controls, LMDD was associated with increased activations in left amygdala (PFWE=0.031,kE=4) and left DLPFC (PFWE=0.002,kE=33), increased mean bilateral amygdala activation (ß=0.0715,P=0.0314), and increased inhibition from left amygdala to left DLPFC, all in response to fearful faces contrasted to baseline. Results did not appear to be attributable to depressive illness severity or antidepressant medication status at scan time. LIMITATIONS: Most studied participants had past rather than current depression, average severity of ongoing depression symptoms was low, and a substantial proportion of participants were receiving medication. The study was not longitudinal and the participants were only assessed a single time. CONCLUSIONS: LMDD is associated with hyperactivity of the amygdala and DLPFC, and with stronger amygdala to DLPFC inhibitory connectivity, all in response to fearful faces, unrelated to depression severity at scan time. These results help reduce inconsistency in past literature and suggest disruption of 'bottom-up' limbic-prefrontal effective connectivity in depression.

Structural brain correlates of childhood trauma with replication across two large, independent community-based samples.

INTRODUCTION: Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts. METHODS: The two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes. RESULTS: Childhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (ß=-0.0385, SE=0.0048, p(FDR)=5.43x10-15) and parietal lobes (ß=-0.0387, SE=0.005, p(FDR)=1.56x10-14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (ß=-0.0232, SE=0.0039, p(FDR)=2.91x10-8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes. DISCUSSION: Associations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.

Metabolite Signature and Differential Expression of Genes in Washington Navel Oranges (Citrus sinensis) Infected by Spiroplasma citri.

Spiroplasma citri is the pathogen that causes citrus stubborn disease (CSD). Infection of citrus with S. citri has been shown to cause leaf mottling, reduce fruit yield, and stunt tree growth. Fruit from trees exhibiting symptoms of CSD are misshapen and discolored. The symptoms of CSD are easily confused with nutrient deficiencies or symptoms of citrus greening disease. In this study, young Washington navel oranges (Citrus sinensis) were graft-inoculated with budwood originating from trees confirmed to be infected with S. citri. Leaf samples were collected monthly for 10 months for metabolomics and differential gene expression analyses. Significant differences in the concentration of metabolites and expressed genes were observed between control and S. citri-infected trees throughout the experiment. Metabolites and genes associated with important defense and stress pathways, including jasmonic acid signaling, cell wall modification, amino acid biosynthesis, and the production of antioxidant and antimicrobial secondary metabolites, were impacted by S. citri throughout the study, and even prior to symptom development. This work fills a current gap in knowledge surrounding the pathogenicity of S. citri and provides an updated mechanistic explanation for the development of CSD symptoms in S. citri-infected plants.

Epigenome-wide association study of global cortical volumes in generation Scotland: Scottish family health study.

A complex interplay of genetic and environmental risk factors influence global brain structural alterations associated with brain health and disease. Epigenome-wide association studies (EWAS) of global brain imaging phenotypes have the potential to reveal the mechanisms of brain health and disease and can lead to better predictive analytics through the development of risk scores.We perform an EWAS of global brain volumes in Generation Scotland using peripherally measured whole blood DNA methylation (DNAm) from two assessments, (i) at baseline recruitment, ~6 years prior to MRI assessment (N = 672) and (ii) concurrent with MRI assessment (N=565). Four CpGs at baseline were associated with global cerebral white matter, total grey matter, and whole-brain volume (Bonferroni p≤7.41×10-8, ßrange = -1.46x10-6 to 9.59 × 10-7). These CpGs were annotated to genes implicated in brain-related traits, including psychiatric disorders, development, and ageing. We did not find significant associations in the meta-analysis of the EWAS of the two sets concurrent with imaging at the corrected level.These findings reveal global brain structural changes associated with DNAm measured ~6 years previously, indicating a potential role of early DNAm modifications in brain structure. Although concurrent DNAm was not associated with global brain structure, the nominally significant findings identified here present a rationale for future investigation of associations between DNA methylation and structural brain phenotypes in larger population-based samples.

Spectral clustering based on structural magnetic resonance imaging and its relationship with major depressive disorder and cognitive ability.

There is increasing interest in using data-driven unsupervised methods to identify structural underpinnings of common mental illnesses, including major depressive disorder (MDD) and associated traits such as cognition. However, studies are often limited to severe clinical cases with small sample sizes and most do not include replication. Here, we examine two relatively large samples with structural magnetic resonance imaging (MRI), measures of lifetime MDD and cognitive variables: Generation Scotland (GS subsample, N = 980) and UK Biobank (UKB, N = 8,900), for discovery and replication, using an exploratory approach. Regional measures of FreeSurfer derived cortical thickness (CT), cortical surface area (CSA), cortical volume (CV) and subcortical volume (subCV) were input into a clustering process, controlling for common covariates. The main analysis steps involved constructing participant K-nearest neighbour graphs and graph partitioning with Markov stability to determine optimal clustering of participants. Resultant clusters were (1) checked whether they were replicated in an independent cohort and (2) tested for associations with depression status and cognitive measures. Participants separated into two clusters based on structural brain measurements in GS subsample, with large Cohen's d effect sizes between clusters in higher order cortical regions, commonly associated with executive function and decision making. Clustering was replicated in the UKB sample, with high correlations of cluster effect sizes for CT, CSA, CV and subCV between cohorts across regions. The identified clusters were not significantly different with respect to MDD case-control status in either cohort (GS subsample: pFDR = .2239-.6585; UKB: pFDR = .2003-.7690). Significant differences in general cognitive ability were, however, found between the clusters for both datasets, for CSA, CV and subCV (GS subsample: d = 0.2529-.3490, pFDR  < .005; UKB: d = 0.0868-0.1070, pFDR  < .005). Our results suggest that there are replicable natural groupings of participants based on cortical and subcortical brain measures, which may be related to differences in cognitive performance, but not to the MDD case-control status.

Blunted medial prefrontal cortico-limbic reward-related effective connectivity and depression.

Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex. However it is unclear whether this finding can be replicated in a large number of subjects. The functional anatomy of the medial prefrontal cortex and basal ganglia has been extensively studied and the former has excitatory glutamatergic projections to the latter. Reduced effect of glutamatergic projections from the prefrontal cortex to the nucleus accumbens has been argued to underlie motivational disorders such as depression, and many prominent theories of major depressive disorder propose a role for abnormal cortico-limbic connectivity. However, it is unclear whether there is abnormal reward-linked effective connectivity between the medial prefrontal cortex and basal ganglia related to depression. While resting state connectivity abnormalities have been frequently reported in depression, it has not been possible to directly link these findings to reward-learning studies. Here, we tested two main hypotheses. First, mood symptoms are associated with blunted striatal reward prediction error signals in a large community-based sample of recovered and currently ill patients, similar to reports from a number of studies. Second, event-related directed medial prefrontal cortex to basal ganglia effective connectivity is abnormally increased or decreased related to the severity of mood symptoms. Using a Research Domain Criteria approach, data were acquired from a large community-based sample of subjects who participated in a probabilistic reward learning task during event-related functional MRI. Computational modelling of behaviour, model-free and model-based functional MRI, and effective connectivity dynamic causal modelling analyses were used to test hypotheses. Increased depressive symptom severity was related to decreased reward signals in areas which included the nucleus accumbens in 475 participants. Decreased reward-related effective connectivity from the medial prefrontal cortex to striatum was associated with increased depressive symptom severity in 165 participants. Decreased striatal activity may have been due to decreased cortical to striatal connectivity consistent with glutamatergic and cortical-limbic related theories of depression and resulted in reduced direct pathway basal ganglia output. Further study of basal ganglia pathophysiology is required to better understand these abnormalities in patients with depressive symptoms and syndromes.

Aspirin moderates the association between cardiovascular risk, brain white matter hyperintensity total lesion volume and processing speed in normal ageing.

OBJECTIVES: Cardiovascular risk is associated with cognitive decline and this effect is attributed to brain pathology, including white matter hyperintensity (WMH) burden. Low-dose aspirin is frequently recommended for reducing vascular events. We investigated the effect of taking aspirin on the association between cardiovascular risk, WMH burden and cognitive function. STUDY DESIGN: The study sample was drawn from 318 dementia-free adults aged 67-71 years. Brain magnetic resonance imaging (MRI) scans were acquired from 239 participants. MAIN OUTCOME MEASURES: WMH total lesion volumes (TLV) were extracted using the automated lesion segmentation algorithm. We measured cardiovascular risk by calculating ASSIGN score. Cognitive ability was measured using a test of processing speed. We developed structural equation models to test our hypothesis. RESULTS: Sixty-eight participants (47.1 % male, mean age = 68.8 years) reported that they took aspirin. The demographic measures did not differ significantly by aspirin use. Among aspirin users, there was a strong negative association between WMH TLV and cognition (ß = -0.43, p-value < 0.001), while in non-users of aspirin the only significant predictor of poorer cognition was cardiovascular risk (ß = -0.17, p-value = 0.001). CONCLUSIONS: Aspirin use moderates the negative effect of WMH burden on cognition. Considering WMH burden in addition to cardiovascular risk could improve the prediction of cognitive decline in older adults with aspirin use.

Chemical and sensory analysis of commercial Navel oranges in California.

Seven lots of commercially available Navel oranges grown in California were evaluated with flavoromic, metabolomic, sensory descriptive analysis, and consumer testing techniques to identify sensory and chemical drivers of liking. Eight identified chemical clusters related to numerous sensory attributes and consumer preferences. Differences in adult and child preferences led to the discovery of six consumer clusters (four adult and two child). Sweetness, overall flavor, sourness, fruity flavor, and juiciness were identified as the main sensory drivers of liking for the consumers. Fructose, glucose, and proline were among the compounds that best explained perceived sweetness while sourness was correlated with citrate and ascorbate. Perceived fruity flavor increased with higher concentrations of ethanol. We conclude that consumers differ in their preferences for Navel oranges and desire fruit that is higher in both sweetness and sourness.

Evaluation of California-Grown Blood and Cara Cara Oranges Through Consumer Testing, Descriptive Analysis, and Targeted Chemical Profiling.

The acceptability of Moro, Tarocco, Cara Cara, Shahani, Bream Tarocco, Boukhobza, and Sanguinelli oranges from both commercial and research orchards was tested with adult (n = 152) and child (n = 72) consumers. Qualitative focus groups were also conducted to understand consumer familiarity and thoughts about the fruit. Sensory descriptive and chemical analyses were carried out to identify drivers of liking. Overall, consumers preferred the lighter colored varieties consisting of Tarocco, Cara Cara, and Boukhobza. One cluster of adults (n = 80) showed preferences towards sweet and fruity flavors and away from sourness and citric acid. The second adult cluster (n = 72) was tolerant of the sour fruit but did not like fruit high in bitterness and flavonoid content. The largest child cluster (n = 42) showed preferences for samples higher in orange and tropical flavors (Cara Cara, Tarocco, and Boukhobza varieties). The appearance of the Cara Cara was strongly liked by the consumer population in both quantitative and qualitative settings. Hunter scale a color values strongly correlated to the higher berry/dried fruit flavors, and concentrations of naringenin. Focus group participants noted that they were relatively unfamiliar with blood oranges. Growers and producers may want to invest in the lighter colored varieties, such as Cara Cara, Tarocco, Boukhobza and Shahani, as these were liked by a majority of consumers and were low in less desirable sensory characteristics, such as bitterness and sourness. PRACTICAL APPLICATION: Through consumer tests, sensory evaluation, and chemical analyses, this research uncovered which sensory properties may drive consumer acceptance of blood and Cara Cara oranges, and informed potential production and marketing strategies for increasing their consumption. This information should benefit the citrus industry as a whole and may enhance the use of specialty oranges by the food, beverage, and food service industries.

Cohort profile for the STratifying Resilience and Depression Longitudinally (STRADL) study: A depression-focused investigation of Generation Scotland, using detailed clinical, cognitive, and neuroimaging assessments.

STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS provides an important opportunity to study complex gene-environment interactions, incorporating linkage to existing datasets and inclusion of early-life variables for two longitudinal birth cohorts. Specifically, data collection in STRADL included: socio-economic and lifestyle variables; physical measures; questionnaire data that assesses resilience, early-life adversity, personality, psychological health, and lifetime history of mood disorder; laboratory samples; cognitive tests; and brain magnetic resonance imaging. Some of the questionnaire and cognitive data were first assessed at the GS:SFHS baseline assessment between 2006-2011, thus providing longitudinal measures of depression and resilience. Similarly, routine NHS data and early-life variables are linked to STRADL data, further providing opportunities for longitudinal analysis. Recruitment has been completed and we consented and tested 1,188 participants.

The association between polypharmacy and late life deficits in cognitive, physical and emotional capability: a cohort study.

Background Polypharmacy is a growing health concern for older adults and is associated with poorer clinical outcome. Objective This study aim is to investigate the association between polypharmacy and impairment in cognitive, physical and emotional capability controlling for the confounding effect of co-morbidities. Setting The Aberdeen 1936 Birth Cohort from 1999 to 2004. Method Recruited were 498 dementia free participants around 64 years old and recruited into wave one. Linear regression and structural equation models were used. Models were adjusted for the effect of age, gender, childhood IQ, education and Body Mass Index. A triad of impairment was defined as a composite measure of impairment in cognitive, physical and emotional function. Main outcome measure The relationships between polypharmacy, co-morbidity and triad of impairment. Results The prevalence of polypharmacy was 12.3% in this relatively healthy sample. Polypharmacy was significantly associated with increased impairment in cognitive, physical and emotional ability (ß = 3.6, p = 0.003) after controlling for the effect of comorbidities and other confounding variables. As expected, higher childhood IQ and educational achievement had protective effects against impairment while higher comorbidity score and Body Mass Index were associated with increased impairment in this population. Conclusions The independent association of polypharmacy and reduced cognitive, physical and emotional capability makes this a promising target for predicting and potentially reducing the risk of impairment and associated healthcare costs in older adults. Longitudinal studies are required to investigate the underlying mechanisms for the observed relationships further.

The Neurobiology of Personal Control During Reward Learning and Its Relationship to Mood.

BACKGROUND: The majority of reward learning neuroimaging studies have not focused on the motivational aspects of behavior, such as the inherent value placed on choice itself. The experience and affective value of personal control may have particular relevance for psychiatric disorders, including depression. METHODS: We adapted a functional magnetic resonance imaging reward task that probed the value placed on exerting control over one's decisions, termed choice value, in 122 healthy participants. We examined activation associated with choice value; personally chosen versus passively received rewards; and reinforcement learning metrics, such as prediction error. Relationships were tested between measures of motivational orientation (categorized as autonomy, control, and impersonal) and subclinical depressive symptoms. RESULTS: Anticipating personal choice activated left insula, cingulate, right inferior frontal cortex, and ventral striatum (pfamilywise error-corrected < .05). Ventral striatal activations to choice were diminished in participants with subclinical depressive symptoms. Personally chosen rewards were associated with greater activation of the insula and inferior frontal gyrus, cingulate cortex, hippocampus, thalamus, and substantia nigra compared with rewards that were passively received. In participants who felt they had little control over their own behavior (impersonal orientation), prediction error signals in nucleus accumbens were stronger during passive trials. CONCLUSIONS: Previous findings regarding personal choice have been verified and advanced through the use of both reinforcement learning models and correlations with psychopathology. Personal choice has an impact on the extended reward network, potentially allowing these clinically important areas to be addressed in ways more relevant to personality styles, self-esteem, and symptoms such as motivational anhedonia.

Increased diastolic blood pressure is associated with MRI biomarkers of dementia-related brain pathology in normative ageing.

Background: hypertension is a risk for brain ageing, but the mechanisms underlying this effect remain unclear. Magnetic resonance imaging (MRI) detected biomarkers of brain ageing include white matter hyperintensities (WMHs), a marker of cerebrovascular disease, and hippocampal volume, a marker of Alzheimer's disease pathology. Objective: to examine relationships between blood pressure (BP) components and brain pathology in older adults. Subjects: two hundred and twenty-seven members of the Aberdeen 1936 Birth Cohort between ages 64 and 68 years. Methods: BP was assessed biennially between 64 and 68 years and brain MRI performed at 68 years. The risk factors of interest were diastolic and systolic BP and their visit-to-visit variability. Outcomes were WMH abundance and hippocampal volume. Regression models, controlling for confounding factors, examined their relationships. Results: higher diastolic BP predicted increased WMH (ß = 0.13, P = 0.044) and smaller hippocampi (ß = -0.25, P = 0.006). In contrast, increased systolic BP predicted larger hippocampi (ß = 0.22, P = 0.013). Variability of diastolic BP predicted lower hippocampal volume (ß = -0.15, P = 0.033). These relationships were independent of confounding life-course risk factors. Anti-hypertensive medication did not modify these relationships, but was independently associated with increased WMH (ß = 0.17, P = 0.011). Conclusion: increased diastolic BP is associated with biomarkers of both cerebrovascular and Alzheimer's diseases, whereas the role of systolic BP is less clear, with evidence for a protective effect on hippocampal volume. These differing relationships emphasise the importance of considering individual BP components with regard to brain ageing and pathology. Interventions targeting diastolic hypertension and its chronic variability may provide new strategies able to slow the accumulation of these harmful pathologies.

Klotho, APOEε4, cognitive ability, brain size, atrophy, and survival: a study in the Aberdeen Birth Cohort of 1936.

A single copy of klotho allele KL-VS is associated with longevity, better health, increased cognition, and bigger regional brain volume. However, its longitudinal effects on cognition and brain volumes, both global and regional, in late life are unclear. In this study we show that, relative to noncarriers, KL-VS heterozygotes had (1) shorter survival; (2) smaller white matter volumes; (3) slower cognitive decline; and (4) greater right frontal lobe volumes. The KL-VS heterozygote survival and white matter volume disadvantages were unexpected. A possible explanation for these results in the context of the literature is a potential interaction between the environment and/or age of the participants, leading to a heterozygote disadvantage. The longitudinal cognitive trajectories indicate that heterozygotes would have an advantage in very late life. Collectively these results suggest that the genotype-survival advantage of the KL-VS allele is age-dependent and possibly mediated through differential cognition and brain volume.

A comparison of measurement methods of hippocampal atrophy rate for predicting Alzheimer's dementia in the Aberdeen Birth Cohort of 1936.

INTRODUCTION: Various methods are available to measure hippocampal atrophy rate. We compared methods to predict Alzheimer's dementia. METHODS: Participants with brain imaging at ages 69 and 73 years were identified from a previous study. Simple manual measures and computationally automated volumetry were performed. Receiver operating characteristics assessed the predictive ability of each method at baseline and on logit regression analysis of two serial scans. RESULTS: Ten of 149 participants developed Alzheimer's dementia and had lower baseline volumes (3647 vs. 4194 mm3P = .002), rates of volume loss (-126 vs. -36 mm3/y; P = .001), and rates of loss in hippocampal fraction (-8.55 vs. -2.35 x 10-5/y; P = .001). Baseline volume with a rate of change gave the highest area under the curve value of 0.96. DISCUSSION: Automated volumetry measuring hippocampal size at age 69 years and subsequent rate of change predicts Alzheimer's dementia development.

An investigation of quality improvement initiatives in decreasing the rate of avoidable 30-day, skilled nursing facility-to-hospital readmissions: a systematic review.

OBJECTIVES: The main objective was to investigate the applicability and effectiveness of quality improvement initiatives in decreasing the rate of avoidable 30-day, skilled nursing facility (SNF)-to-hospital readmissions. PROBLEM: The rate of rehospitalizations from SNF within 30 days of original discharge has increased within the last decade. SETTING: The research team participants conducted a literature review via Cumulative Index of Nursing and Allied Health Literature and PubMed to collect data about quality improvement implemented in SNFs. RESULTS: The most common facilitator was the incorporation of specialized staff. The most cited barriers were quality improvement tracking and implementation. CONCLUSION: These strategy examples can be useful to acute care hospitals attempting to lower bounce back from subacute care providers and long-term care facilities seeking quality improvement initiatives to reduce hospital readmissions.

A Review of Frailty Syndrome and Its Physical, Cognitive and Emotional Domains in the Elderly.

BACKGROUND: Frailty, a very important complication of increasing age, is a well-recognised concept although it has not been accurately measured in the clinical setting. The aim of this literature review is to summarise commonly used frailty screening tools, and to describe how new measurement methods have been developed recently. METHODS: Several frailty measurement tools including the most cited and newly developed scales have been described in this review. We searched the MEDLINE using the search terms; "frailty score, scale, tool, instrument, index, phenotype" and then summarised selected tools for physical, cognitive, emotional and co-morbidity domains. RESULTS: The most cited frailty measurement methods developed from 1999 to 2005 are primarily criteria for physical frailty (e.g., frailty phenotype). More recently developed tools (e.g., triad of impairment and multidimensional frailty score) consider cognitive and emotional domains in addition to physical deficit in measuring frailty. Co-morbidity has also been considered as a domain of frailty in several measurement tools. CONCLUSION: Although frailty tools have traditionally assessed physical capability, cognitive and emotional impairment often co-exist in older adults and may have shared origins. Therefore, newer tools which provide a composite measure of frailty may be more relevant for future use.