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This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression.
A genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study.
Longitudinal, naturalistic follow-up study.
Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center.
The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery was administered to the study participants at baseline and a minimum of twice within a subsequent 3-year period in order to measure cognitive decline. A GWAS analysis was conducted to identify genetic variation that is associated with baseline and change in the CERAD Total Score (CERAD-TS) in NCODE.
The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (p = 3.7 × 10−7; false discovery rate q = 0.0371). For each additional G allele, average baseline CERAD-TS decreased by 8.656 points. The most significant SNP that lies within a gene was rs11666579 in SLC27A1 (p = 1.1 × 10−5). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. SLC27A1 is involved with processing docosahexaenoic acid (DHA), an endogenous neuroprotective compound in the brain. Decreased levels of DHA have been associated with the development of Alzheimer’s disease. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in GRXCR1 (p = 1.1 × 10−6), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing.
Our GWAS of cognitive function and decline among individuals with late-life depression (LLD) has identified promising candidate genes that, upon replication in other cohorts of LLD, may be potential biomarkers for cognitive decline and suggests DHA supplementation as a possible therapy of interest.
Current sea-level rise partly stems from increased surface melting and meltwater runoff from the Greenland ice sheet. Multi-year snow, also known as firn, covers about 80% of the ice sheet and retains part of the surface meltwater. Since the firn cold content integrates its physical and thermal characteristics, it is a valuable tool for determining the meltwater-retention potential of firn. We use gap-filled climatological data from nine automatic weather stations in the ice-sheet accumulation area to drive a surface-energy-budget and firn model, validated against firn density and temperature observations, over the 1998–2017 period. Our results show a stable top 20 m firn cold content (CC20) at most sites. Only at the lower-elevation Dye-2 site did CC20 decrease, by 24% in 2012, before recovering to its original value by 2017. Heat conduction towards the surface is the main process feeding CC20 at all nine sites, while CC20 reduction occurs through low-cold-content fresh-snow addition at the surface during snowfall and latent-heat release when meltwater refreezes. Our simulations suggest that firn densification, while reducing pore space for meltwater retention, increases the firn cold content, enhances near-surface meltwater refreezing and potentially sets favourable conditions for ice-slab formation.
Aim of this contribution is to describe the intervention used in the study “Effectiveness and Cost-Effectiveness of Needs-Oriented Discharge Planning and Monitoring for High Utilisers of Psychiatric Services” (NODPAM). This intervention applies principles of needs-led care and focusses on the inpatient-outpatient transition. The NODPAM intervention manual includes a range of predefined standardised options based on number and type of needs.
For the intervention group, a trained intervention worker provides a coherent package of needs-oriented discharge planning and monitoring focussing on the care process. He or she emphasises continuity of the care process vis-à-vis both patient and clinician (and carers if possible) via providing two manualised intervention sessions): (a) A discharge planning session takes place just before discharge with the patient and responsible clinician at the inpatient service; (b) A monitoring session takes place three months after discharge with the patient and outpatient clinician (office-based or public outpatient mental health service-based). A written treatment plan is signed by and forwarded to all participants after each session.
Acceptance of the intervention by patients and clinicians has been high so far. Further results on duration, participant characteristics, and participants' appraisal of the NODPAM intervention will be presented.
These first results indicate that the NODPAM intervention is feasible in inpatient mental health services in Germany. Discussion will focus on its applicability in other service systems.
The evidence linking low-carbohydrate diets (LCD) to CVD is controversial, and results from epidemiological studies are inconsistent. We aimed to assess the relationship between LCD patterns and coronary artery Ca (CAC) scores from computed tomography in the Multi-Ethnic Study of Atherosclerosis cohort. Our sample included 5614 men and women free of clinical CVD at baseline (2000–2002), who had a FFQ, a baseline measure and ≥1 measure of CAC during follow-up. We excluded those with implausible energy intake or daily physical activity. The overall, animal-based and plant-based LCD scores were calculated based on intakes of macronutrients. Relative risk regression and robust regression models were used to examine the cross-sectional and longitudinal relationship between LCD score quintile and CAC outcomes, after adjustment for multiple cardiovascular risk factors. The mean age of participants was 63 years. The median intakes of total carbohydrate, fat and protein were 53·7, 30·5 and 15·6 % energy/d, respectively. Among 2892 participants with zero CAC scores at baseline, 264 developed positive scores during 2·4-year follow-up (11–59 months). Among those with positive scores at baseline, the median increase in CAC was 47 units over the course of follow-up. The overall, the animal-based and the plant-based LCD scores were not associated with CAC prevalence, incidence and progression. In conclusion, diets low in carbohydrate and high in fat and/or protein, regardless of the sources of protein and fat, were not associated with higher levels of CAC, a validated predictor of cardiovascular events, in this large multi-ethnic cohort.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Anxiety is among the most frequently studied emotions in second language acquisition (SLA). Study abroad (SA) researchers have examined its effects on SLA in that setting in a number of studies. The current study goes beyond previous SA research by examining how anxiety develops and connects with language proficiency development over SA. Specifically, it uses anxiety-related measures of foreign language classroom anxiety (FLCA), foreign language enjoyment (FLE), and a physiological manifestation of anxiety (hair cortisol). As far as the classroom is concerned, learners grew more comfortable, experiencing less anxiety and more enjoyment over the period of SA. However, learners showed physiological signs of overall elevated anxiety despite these increasing classroom comfort levels. Two key factors that may have influenced their anxiety levels abroad were tendency toward anxiety prior to SA and language proficiency upon departure for SA. The latter provides support for having students more proficient prior to SA, since doing so may lead to less anxiety during SA.
Safeguarding threatened species in captivity is a promising management approach, but evaluating the performance of captive programmes is essential to assess reintroduction potential. The eastern population of the Northern Bald Ibis, Geronticus eremita, used to be a locally common migratory bird species, but catastrophic population declines throughout the past century have resulted in a single population in southern Turkey that forages freely during summer but only survives in captivity during winter. We examined whether breeding success of this semi-wild colony was comparable to breeding success of previous wild populations, and to what extent breeding success was influenced by supplementary feeding and wild foraging in habitats near the breeding station. Average productivity from 2009 to 2015 was 1.12 fledglings per nesting pair (range 0.96–1.19). In 2013 and 2014, there was no correlation between attendance at supplementary feeding events and productivity, and breeding birds attended on average only 35% of supplementary feeding events. Birds that were frequently observed at a local tree nursery raised fewer offspring, while birds observed more frequently in poldered cultivation, and in particular in mint crops or in fields covered with manure, raised on average more offspring. Foraging success was highest in meadows and cropland, particularly in mint crops and fields covered in manure, and lowest at the tree nursery. We speculate that selection of highly suitable wild foraging habitat such as mint crops or fields covered in manure allows the Northern Bald Ibis to raise more fledglings than exclusive reliance on supplementary food provided at the breeding station. Establishing a second breeding colony of this species in Turkey will therefore require a careful assessment of the suitability of wild foraging habitat in the vicinity of suitable nesting opportunities.
The role of episodic mass loss in evolved massive stars is one of the outstanding questions in stellar evolution theory. Integral field spectroscopy of nebulae around massive stars provide information on their recent mass-loss history. η Car is one of the most massive evolved stars and is surrounded by a complex circumstellar environment. We have conducted a three-dimensional morpho-kinematic analysis of η Car’s ejecta outside its famous Homunculus nebula. SHAPE modelling of VLT MUSE data establish unequivocally the spatial cohesion of the outer ejecta and the correlation of ejecta with the soft X-ray emission.
Glacier surface mass-balance measurements on Greenland started more than a century ago, but no compilation exists of the observations from the ablation area of the ice sheet and local glaciers. Such data could be used in the evaluation of modelled surface mass balance, or to document changes in glacier melt independently from model output. Here, we present a comprehensive database of Greenland glacier surface mass-balance observations from the ablation area of the ice sheet and local glaciers. The database spans the 123 a from 1892 to 2015, contains a total of ~3000 measurements from 46 sites, and is openly accessible through the PROMICE web portal (http://www.promice.dk). For each measurement we provide X, Y and Z coordinates, starting and ending dates as well as quality flags. We give sources for each entry and for all metadata. Two thirds of the data were collected from grey literature and unpublished archive documents. Roughly 60% of the measurements were performed by the Geological Survey of Denmark and Greenland (GEUS, previously GGU). The data cover all regions of Greenland except for the southernmost part of the east coast, but also emphasize the importance of long-term time series of which there are only two exceeding 20 a. We use the data to analyse uncertainties in point measurements of surface mass balance, as well as to estimate surface mass-balance profiles for most regions of Greenland.
We investigate the international linkages of uncertainty associated with the long-term movements of inflation. In the first step, we establish that inflation uncertainty in the G7 is intertwined, and the degree of synchronization has increased during the recent two decades. We also document a rise in inflation uncertainty accompanying the global financial crisis. Based on a factor–structural vector autoregression, we provide evidence of a common international shock. We disclose that this shock is closely related to oil and commodity price uncertainty, and it explains large parts of the recent rise in inflation uncertainty. Moreover, increased synchronization can be explained by greater relative importance of this global shock. We also document that inflation uncertainty has become more stable, because domestic shocks translate less extensively into individual economies. This finding lends support to the “good policy” hypothesis.
Depression in late life is a risk factor for cognitive decline. Depression is also associated with increased disability and social support deficits; these may precede conversion to dementia and inform risk. In this study, we examined if baseline or one-year change in disability and social support predicted later cognitive deterioration.
299 cognitively intact depressed older adults were followed for an average of approximately seven years. Participants received antidepressant treatment according to a standardized algorithm. Neuropsychological testing and assessment of disability and social support were assessed annually. Cognitive diagnosis was reviewed annually at a consensus conference to determine if participants remained cognitively normal, or if they progressed to either dementia or cognitively impaired, no dementia (CIND).
During study participation, 167 individuals remained cognitively normal (56%), 83 progressed to CIND (28%), and 49 progressed to dementia (16%). Greater baseline instrumental activities of daily living (IADL) deficits predicted subsequent conversion to a cognitive diagnosis (CIND or dementia). However, neither baseline measures nor one-year change in basic ADLs (BADLs) and social support predicted cognitive conversion. In post hoc analyses, two IADL measures (managing finances, preparing meals) significantly increased the odds of cognitive conversion.
Greater IADL deficits predicted increased risk of cognitive conversion. Assessment of IADL deficits may provide clues about risk of later cognitive decline.
In this response to commentaries, we revisit the two main arguments of our target article. Based on data drawn from a variety of research areas – vocal behavior in nonhuman primates, speech physiology and pathology, neurobiology of basal ganglia functions, motor skill learning, paleoanthropological concepts – the target article, first, suggests a two-stage model of the evolution of the crucial motor prerequisites of spoken language within the hominin lineage: (1) monosynaptic refinement of the projections of motor cortex to brainstem nuclei steering laryngeal muscles, and (2) subsequent “vocal-laryngeal elaboration” of cortico-basal ganglia circuits, driven by human-specific FOXP2 mutations. Second, as concerns the ontogenetic development of verbal communication, age-dependent interactions between the basal ganglia and their cortical targets are assumed to contribute to the time course of the acquisition of articulate speech. Whereas such a phylogenetic reorganization of cortico-striatal circuits must be considered a necessary prerequisite for ontogenetic speech acquisition, the 30 commentaries – addressing the whole range of data sources referred to – point at several further aspects of acoustic communication which have to be added to or integrated with the presented model. For example, the relationships between vocal tract movement sequencing – the focus of the target article – and rhythmical structures of movement organization, the connections between speech motor control and the central-auditory and central-visual systems, the impact of social factors upon the development of vocal behavior (in nonhuman primates and in our species), and the interactions of ontogenetic speech acquisition – based upon FOXP2-driven structural changes at the level of the basal ganglia – with preceding subvocal stages of acoustic communication as well as higher-order (cognitive) dimensions of phonological development. Most importantly, thus, several promising future research directions unfold from these contributions – accessible to clinical studies and functional imaging in our species as well as experimental investigations in nonhuman primates.
The Mediterranean diet has been reported to be inversely associated with incident metabolic syndrome (MetSyn) among older adults; however, this association has not been studied in young African American and white adults. The objective of the present study was to evaluate the association of a modified Mediterranean diet (mMedDiet) score with the 25-year incidence of the MetSyn in 4713 African American and white adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. A diet history questionnaire was used to assess dietary intake at baseline, year 7 and year 20 and a mMedDiet score was created. Cardiovascular risk factors were measured at multiple examinations over 25 years. The MetSyn was defined according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. Cox proportional-hazards regression analysis was use to evaluate associations for incident MetSyn across the mMedDiet score categories adjusting for demographic characteristics, lifestyle factors and BMI. Higher mMedDiet scores represented adherence to a dietary pattern rich in fruit, vegetables, whole grains, nuts and fish, but poor in red and processed meat and snack foods. The incidence of MetSyn components (abdominal obesity, elevated TAG concentrations and low HDL-cholesterol concentrations) was lower in those with higher mMedDiet scores than in those with lower scores. Furthermore, the incidence of the MetSyn was lower across the five mMedDiet score categories; the hazard ratios and 95 % CI from category 1 to category 5 were 1·0; 0·94 (0·76, 1·15); 0·84 (0·68, 1·04); 0·73 (0·58, 0·92); and 0·72 (0·54, 0·96), respectively (Ptrend= 0·005). These findings suggest that the risk of developing the MetSyn is lower when consuming a diet rich in fruit, vegetables, whole grains, nuts and fish.
Dietary protein has been shown to increase urinary Ca excretion in randomised controlled trials, and diets high in protein may have detrimental effects on bone health; however, studies examining the relationship between dietary protein and bone health have conflicting results. In the present study, we examined the relationship between dietary protein (total, animal and vegetable protein) and lumbar spine trabecular volumetric bone mineral density (vBMD) among participants enrolled in the Multi-Ethnic Study of Atherosclerosis (n 1658). Protein intake was assessed using a FFQ obtained at baseline examination (2000–2). Lumbar spine vBMD was measured using quantitative computed tomography (2002–5), on average 3 years later. Multivariable linear and robust regression techniques were used to examine the associations between dietary protein and vBMD. Sex and race/ethnicity jointly modified the association of dietary protein with vBMD (P for interaction = 0·03). Among white women, higher vegetable protein intake was associated with higher vBMD (P for trend = 0·03), after adjustment for age, BMI, physical activity, alcohol consumption, current smoking, educational level, hormone therapy use, menopause and additional dietary factors. There were no consistently significant associations for total and animal protein intakes among white women or other sex and racial/ethnic groups. In conclusion, data from the present large, multi-ethnic, population-based study suggest that a higher level of protein intake, when substituted for fat, is not associated with poor bone health. Differences in the relationship between protein source and race/ethnicity of study populations may in part explain the inconsistent findings reported previously.
Given the high intake levels of soya and low incidence rates of breast cancer in Asian countries, isoflavones, substances with an oestrogen-like structure occurring principally in soyabeans, are postulated to be cancer protective. In the present study, we examined the association of dietary isoflavone intake with breast cancer risk in 84 450 women (896 in situ and 3873 invasive cases) who were part of the Multiethnic Cohort (Japanese Americans, whites, Latinos, African Americans and Native Hawaiians) with a wide range of soya intake levels. The absolute levels of dietary isoflavone intake estimated from a baseline FFQ were categorised into quartiles, with the highest quartile being further subdivided to assess high dietary intake. The respective intake values for the quartiles (Q1, Q2, Q3, and lower and upper Q4) were 0– < 3·2, 3·2– < 6·7, 6·7– < 12·9, 12·9– < 20·3, and 20·3–178·7 mg/d. After a mean follow-up period of 13 years, hazard ratios (HR) and 95 % CI were calculated using Cox regression models stratified by age and adjusted for known confounders. Linear trends were tested by modelling continuous variables of interest assigned the median value within the corresponding quartile. No statistically significant association was observed between dietary isoflavone intake and overall breast cancer risk (HR for upper Q4 v. Q1: 0·96 (95 % CI 0·85, 1·08); P trend = 0·40). While the test for interaction was not significant (P= 0·14), stratified analyses suggested possible ethnic/racial differences in risk estimates, indicating that higher isoflavone intakes may be protective in Latina, African American and Japanese American women. These results are in agreement with those of previous meta-analyses showing no protection of isoflavones at low intake levels, but suggesting inverse associations in populations consuming high amounts of soya.
Memory impairment in geriatric depression is understudied, but may identify individuals at risk for development of dementia and Alzheimer's disease (AD). Using a neuropsychologically based definition of amnestic mild cognitive impairment (aMCI) in patients with geriatric depression, we hypothesized that patients with aMCI, compared with those without it, would have increased incidence of both dementia and AD.
Participants were aged 60 years and older and consisted of depressed participants and non-depressed volunteer controls. The depressed cohort met criteria for unipolar major depression. All participants were free of dementia and other neurological illness at baseline. At study entry, participants were administered a standardized clinical interview, a battery of neurocognitive tests, and provided a blood sample for determination of apolipoprotein E genotype. A cognitive diagnosis was assigned by a panel of experts who convened annually and reviewed available clinical, neuropsychological and laboratory data to achieve a consensus cognitive diagnosis to determine a consensus diagnosis. Survival analysis examined the association between aMCI and later dementia (all-cause) and AD.
Among 295 depressed individuals, 63 (21.36%) met criteria for aMCI. Among 161 non-depressed controls, four (2.48%) met aMCI criteria. Participants were followed for 6.28 years on average. Forty-three individuals developed dementia, including 40 (13.6%) depressed and three (1.9%) control participants. Both aMCI and age were associated with incident dementia and AD.
The presence of aMCI is a poor prognostic sign among patients with geriatric depression. Clinicians should carefully screen elderly depressed adults for memory impairment.
Any account of “what is special about the human brain” (Passingham 2008) must specify the neural basis of our unique ability to produce speech and delineate how these remarkable motor capabilities could have emerged in our hominin ancestors. Clinical data suggest that the basal ganglia provide a platform for the integration of primate-general mechanisms of acoustic communication with the faculty of articulate speech in humans. Furthermore, neurobiological and paleoanthropological data point at a two-stage model of the phylogenetic evolution of this crucial prerequisite of spoken language: (i) monosynaptic refinement of the projections of motor cortex to the brainstem nuclei that steer laryngeal muscles, presumably, as part of a “phylogenetic trend” associated with increasing brain size during hominin evolution; (ii) subsequent vocal-laryngeal elaboration of cortico-basal ganglia circuitries, driven by human-specific FOXP2 mutations.;>This concept implies vocal continuity of spoken language evolution at the motor level, elucidating the deep entrenchment of articulate speech into a “nonverbal matrix” (Ingold 1994), which is not accounted for by gestural-origin theories. Moreover, it provides a solution to the question for the adaptive value of the “first word” (Bickerton 2009) since even the earliest and most simple verbal utterances must have increased the versatility of vocal displays afforded by the preceding elaboration of monosynaptic corticobulbar tracts, giving rise to enhanced social cooperation and prestige. At the ontogenetic level, the proposed model assumes age-dependent interactions between the basal ganglia and their cortical targets, similar to vocal learning in some songbirds. In this view, the emergence of articulate speech builds on the “renaissance” of an ancient organizational principle and, hence, may represent an example of “evolutionary tinkering” (Jacob 1977).
The association between disability and depression is complex, with disability well established as a correlate and consequence of late life depression. Studies in community samples report that greater volumes of cerebral white matter hyperintensities (WMHs) seen on brain imaging are linked with functional impairment. These vascular changes are also associated with late life depression, but it is not known if depression is a modifier in the relationship between cerebrovascular changes and functional impairment.
The study sample was 237 older adults diagnosed with major depression and 140 never depressed comparison adults, with both groups assessed at study enrollment. The dependent variable was the number of limitations in basic activities of daily living (ADL), instrumental ADLs, and mobility tasks. The independent variable was the total volume of cerebral white matter lesions or hyperintensities assessed though magnetic resonance imaging.
In analyses controlling for age, sex, race, high blood pressure, and cognitive status, a greater volume of WMH was positively associated with the total number of functional limitations as well as the number of mobility limitations among those older adults with late life depression but not among those never depressed, suggesting the association between WMH volume and functional status differs in the presence of late life depression.
These findings suggest older patients with both depression and vascular risk factors may be at an increased risk for functional decline, and may benefit from management of both cerebrovascular risk factors and depression.