Dementia diagnosis and referral in general practice: a representative survey of Irish general practitioners

Aims: Most of those with a memory problem or concern over cognition present to their General Practitioner (GP) in the first instance. Despite this, the current diagnostic and referral patterns of Irish GPs remains unclear. Methods: A survey was distributed to three separate cohorts of GPs (n=692) Results: Ninety-Five (14%) responded. Most personally diagnose 1-3 (69%; 65/95) or 4-6 (21%; 20/95) patients with dementia per year. Two-thirds (62%; 59/95) refer >80% of those with possible dementia for further assessment/support, most commonly to support/clarify a diagnosis (71%; 67/95) and most frequently to a geriatrician (79%; 75/95). In half of cases (51%; 48/95), referral is to a professional working as part of an established memory clinic. One-fifth reported receiving dementia-specific postgraduate training (19%; 18/95) and over four-fifths (82%; 78/95) would welcome further training. Discussion: Further attention to the ongoing establishment of memory clinic services and dedicated referral pathways, as well as increasing emphasis on dementia assessment and diagnosis in medical curricula, is warranted

Energy and eventhood: the infrastructural set piece

‘Energy and Eventhood’ considers the relationship between infrastructure and the cinematic set piece. It proposes a working definition of the set piece as a distinctly (and perhaps excessively) effortful passage or sequence, and reflects on the tendency for narrative films to incorporate infrastructural sites and structures—such as bridges, dams and pipelines—into such set pieces. A number of writers on infrastructure, as both a cultural phenomenon and a representational object, have noted the aesthetic challenge of rendering it as visible and locatable; this article examines how that difficulty becomes manifest in the infrastructural set piece. It takes as its case studies Unstoppable (2010) and Night Moves (2013), two films noted for their distinctive rhythmic expressiveness, and each one deploying the convention of the set piece in ways which exemplify and reflect on the resistance of infrastructure to narrative containment

Long‐term anticholinergic, benzodiazepine and Z‐drug use in community‐dwelling older adults: What is the impact on cognitive and neuropsychological performance?

BACKGROUND Long-term use of anticholinergics, benzodiazepines and related drugs (or "Z-drugs") have been associated with cognitive impairment and dementia. However, the relationship of these medications with cognitive function and domain-specific neuropsychological performance in older adults without dementia, is unclear. METHODS 5135 older adults (74.0 ± 8.3 years; 67.4% female) without a diagnosis of dementia were recruited in Ireland to the Trinity-Ulster-Department of Agriculture (TUDA) study. Detailed cognitive and neuropsychological assessment was conducted using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RESULTS A total of 44% (2259 of 5153) used either a potential or definite anticholinergic medication. Overall, 9.7% (n = 500) used a definite anticholinergic medication. Regular benzodiazepine use was reported by 7% (n = 363), whilst 7.5% (n = 387) used a "Z-drug". Use of definite, but not potential anticholinergic medication was associated with poorer performance on all three assessments (β: -0.09; 95% CI: -0.14, -0.03, p = 0.002 for MMSE; β: -0.04; 95% CI: -0.06, -0.02; p < 0.001 for FAB; β: -4.15; 95% CI: -5.64, -2.66; p < 0.001 for RBANS) in addition to all domains of the RBANS. Regular benzodiazepine use was also associated with poorer neuropsychological test performance, especially in Immediate Memory (β: -4.98; 95% CI: -6.81, -3.15; p < 0.001) and Attention (β: -6.81; 95% CI: -8.60, -5.03; p < 0.001) RBANS domains. CONCLUSIONS Regular use of definite anticholinergic medications and benzodiazepines, but not potential anticholinergics or "Z-drugs", was associated with poorer overall and domain-specific neuropsychological performance in older adults

Gait Characteristics and Cognitive Function in Middle-Aged Adults With and Without Type 2 Diabetes Mellitus: Data from ENBIND

Type 2 Diabetes Mellitus (T2DM) in midlife is associated with a greater risk of dementia in later life. Both gait speed and spatiotemporal gait characteristics have been associated with later cognitive decline in community-dwelling older adults. Thus, the assessment of gait characteristics in uncomplicated midlife T2DM may be important in selecting-out those with T2DM at greatest risk of later cognitive decline. We assessed the relationship between Inertial Motion Unit (IMUs)- derived gait characteristics and cognitive function assessed via Montreal Cognitive Assessment (MOCA)/detailed neuropsychological assessment battery (CANTAB) in middle-aged adults with and without uncomplicated T2DM using both multivariate linear regression and a neural network approach. Gait was assessed under (i) normal walking, (ii) fast (maximal) walking and (iii) cognitive dual-task walking (reciting alternate letters of the alphabet) conditions. Overall, 138 individuals were recruited (n = 94 with T2DM; 53% female, 52.8 8.3 years; n = 44 healthy controls, 43% female, 51.9 8.1 years). Midlife T2DM was associated with significantly slower gait velocity on both slow and fast walks (both p \u3c 0.01) in addition to a longer stride time and greater gait complexity during normal walk (both p \u3c 0.05). Findings persisted following covariate adjustment. In analyzing cognitive performance, the strongest association was observed between gait velocity and global cognitive function (MOCA). Significant associations were also observed between immediate/delayed memory performance and gait velocity. Analysis using a neural network approach did not outperform multivariate linear regression in predicting cognitive function (MOCA) from gait velocity. Our study demonstrates the impact of uncomplicated T2DM on gait speed and gait characteristics in midlife, in addition to the striking relationship between gait characteristics and global cognitive function/memory performance in midlife. Further studies are needed to evaluate the longitudinal relationship between midlife gait characteristics and later cognitive decline, which may aid in selecting-out those with T2DM at greatest-risk for preventative interventions

Reduced Kidney Function is Associated with Poorer Domain‐Specific Cognitive Performance in Community‐Dwelling Older Adults

OBJECTIVES: Whilst chronic kidney disease has been associated with cognitive impairment, the association between reduced estimated Glomerular Filtration Rate (eGFR) and domain‐specific cognitive performance is less clear and may represent an important target for the promotion of optimal brain health in older adults. METHODS: Participants aged >60 years from the Trinity‐Ulster‐Department of Agriculture study underwent detailed cognitive assessment using the Mini‐Mental State Examination (Mini‐Mental State Examination (MMSE)), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Poisson and linear regression models assessed the relationship between eGFR strata and cognitive performance. RESULTS: In 4887 older adults (73.9 ± 8.3 years; 67.7% female), declining eGFR strata was associated with greater likelihood of error on the MMSE/FAB and poorer overall performance on the RBANS. Following robust covariate adjustment, findings were greatest for GFR 80 years. CONCLUSIONS: Reduced kidney function was associated with poorer global and domain‐specific neuropsychological performance. Associations were strongest with eGFR <45 ml/min/1.73 m(2) and in those aged 60–70 years, suggesting that this population may potentially benefit from potential multi‐domain interventions aimed at promoting optimal brain health in older adults

Antidepressant use and orthostatic hypotension in older adults living with mild-to-moderate Alzheimer disease

Objectives: Antidepressant use is often reported as a risk factor for Orthostatic Hypotension (OH), however this relationship has never been explored in those with mild/moderate Alzheimer Disease (AD), who may represent a particularly vulnerable cohort. Methods: We performed a cross‐sectional analysis of baseline data from the NILVAD study. Participants with mild‐moderate AD were recruited from 23 centres in nine countries. Systolic and Diastolic Blood Pressure (SBP/DBP) was recorded in the seated position and after both 1 and 5 minutes of standing. OH was defined as a drop of ≥20 mmHg SBP/≥10 mmHg DBP. We examined the relationship between antidepressant use, orthostatic BP drop and the presence of OH, controlling for important covariates. Results: Of 509 participants (72.9 ± 8.3 years, 61.9% female), two‐fifths (39.1%; 199/509) were prescribed a regular antidepressant. Antidepressant use was associated with a significantly greater SBP and DBP drop at 5 minutes (β: 1.83, 0.16‐3.50, P = .03 for SBP; β: 1.13, 0.02‐2.25, P < .05 for DBP). Selective Serotonin Reuptake Inhibitor (SSRI) use was associated with a significantly greater likelihood of OH (OR 2.0, 1.1‐3.6, P = .02). Both findings persisted following robust covariate adjustment. Conclusions: In older adults with AD, antidepressants were associated with a significantly greater SBP/DBP drop at 5 minutes. SSRI use in particular may be a risk factor for OH. This emphasises the need to screen older antidepressant users, and particularly those with AD, for ongoing orthostatic symptoms in order to reduce the risk of falls in this vulnerable cohort

Planar chiral pseudo-isocoumarins by copper catalysed desymmetrisation

A new copper catalysed desymmetrisation reaction of bisalkynyl ferrocenecarboxylic acids results in the first asymmetric synthesis of planar chiral pseudo-isocoumarins in up to 64 % enantiomeric excess and up to 99 % yield. The absolute configuration of the chiral heterocycles is proven by chemical correlation and circular dichroism spectroscopy, opening the way for the rational extension of this method to produce bioactive isocoumarin-fused ferrocene derivatives

Characterisation of the pro-inflammatory cytokine signature in severe COVID-19

Clinical outcomes from infection with SARS-CoV-2, the cause of the COVID-19 pandemic, are remarkably variable ranging from asymptomatic infection to severe pneumonia and death. One of the key drivers of this variability is differing trajectories in the immune response to SARS-CoV-2 infection. Many studies have noted markedly elevated cytokine levels in severe COVID-19, although results vary by cohort, cytokine studied and sensitivity of assay used. We assessed the immune response in acute COVID-19 by measuring 20 inflammatory markers in 118 unvaccinated patients with acute COVID-19 (median age: 70, IQR: 58-79 years; 48.3% female) recruited during the first year of the pandemic and 44 SARS-CoV-2 naïve healthy controls. Acute COVID-19 was associated with marked elevations in nearly all pro-inflammatory markers, whilst eleven markers (namely IL-1β, IL-2, IL-6, IL-10, IL-18, IL-23, IL-33, TNF-α, IP-10, G-CSF and YKL-40) were associated with disease severity. We observed significant correlations between nearly all markers elevated in those infected with SARS-CoV-2 consistent with widespread immune dysregulation. Principal component analysis highlighted a pro-inflammatory cytokine signature (with strongest contributions from IL-1β, IL-2, IL-6, IL-10, IL-33, G-CSF, TNF-α and IP-10) which was independently associated with severe COVID-19 (aOR: 1.40, 1.11-1.76, p=0.005), invasive mechanical ventilation (aOR: 1.61, 1.19-2.20, p=0.001) and mortality (aOR 1.57, 1.06-2.32, p = 0.02). Our findings demonstrate elevated cytokines and widespread immune dysregulation in severe COVID-19, adding further evidence for the role of a pro-inflammatory cytokine signature in severe and critical COVID-19

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected