The heterogeneity of subjective cognitive decline: A data‐driven approach on a population‐based sample

AbstractBackgroundSubjective Cognitive Decline (SCD) has been largely studied as a risk condition for cognitive decline, mainly in memory clinics or research settings. SCD samples are highly heterogeneous, including both individuals with early Alzheimer's disease and others with psychological vulnerabilities and/or physical comorbidity. Aims: identify distinct SCD subgroups in a population‐based sample of cognitively normal (CN) older adults; explore cross‐sectional differences among SCD subgroups and controls (noSCD); investigate the effect of SCD status on 8‐year cognitive changes.MethodThe InveCe.Ab population‐based study (NCT01345110) enrolled people aged 70‐74 years residing in Abbiategrasso (Milan). Participants underwent multidimensional assessment (blood sampling, lifestyle interview, medical and neuropsychological assessment) at baseline (Nov 2009‐Jan 2011) and after 2, 4 and 8 years. CN participants at baseline completing at least 60% of neuropsychological assessment were included in the present investigation. Those reporting any cognitive complaints to the geriatrician were classified as SCD. Hierarchical cluster analysis was conducted in SCD including 9 relevant variables: education, depressive symptoms, cardiovascular risk, comorbidity, subjective cognitive complaints (numbers) and 4 neuropsychological scores measuring memory, executive functions, visuospatial abilities and language respectively. Cross‐sectional differences among the SCD subgroups identified and noSCD were performed using Kruskal‐Wallis test. Longitudinal cognitive changes according to baseline SCD status (noSCD, SCD subgroups) were estimated using linear mixed models, adjusted for age and education.ResultTwo clusters were identified in SCD. Table 1 shows cross‐sectional results. SCD1 (N=141), compared to SCD2 and CN, were less educated, have higher comorbidities, depressive symptoms and SCD complaints. SCD1 showed lower performances on executive and visuospatial functions, while SCD2, despite being healthier and more educated, showed reduced episodic memory. At longitudinal analysis, all cognitive functions declined due to aging (Time; p<.001). SCD2 displayed a steeper worsening on executive function (Group*Time; p<.001).ConclusionThe presence of SCD at the population level could be informative of future cognitive decline when reported by individuals with higher education. Future studies are needed to clarify the meaning of this condition in the aged population, in order to identify early those at increased risk of actual cognitive decline

Life during COVID-19 lockdown in Italy: the influence of cognitive state on psychosocial, behavioral and lifestyle profiles of older adults.

Few studies have examined lockdown effects on the way of living and well-being of older adults stratified by cognitive state. Since cognitive deficits are common in this population, we investigated how cognition influenced their understanding of the pandemic, socio-behavioral responses and lifestyle adaptations during lockdown, and how these factors affected their mood or memory.Telephone-based survey involving 204 older adults ≥65 y/o (median: 82) with previous assessments of cognitive state: 164 normal-old (NOLD), 24 mild-neurocognitive disorder (mild-NCD), 18 mild-moderate dementia. A structured questionnaire was developed to assess psychological and socio-behavioral variables. Logistic regression was used to ascertain their effects on mood and memory.With increasing cognitive deficits, understanding of the pandemic and the ability to follow lockdown policies, adapt to lifestyle changes, and maintain remote interactions decreased. Participants with dementia were more depressed; NOLDs remained physically and mentally active but were more bored and anxious. Sleeping and health problems independently increased the likelihood of depression (OR: 2.29; CI: 1.06-4.93;NOLD and mild-NCD groups showed similar mood-behavioral profiles suggesting better tolerance of lockdown. Those with dementia were unable to adapt and suffered from depression and cognitive complaints. To counteract lockdown effects, physical and mental activities and digital literacy should be encouraged

Fragment Based Design of New H 4 Receptor-Ligands with Anti-inflammatory Properties in Vivo

Using a previously reported flexible alignment model we have designed, synthesized, and evaluated a series of compounds at the human histamine H 4 receptor (H 4 R) from which 2-(4-methyl-piperazin-1-yl)-quinoxaline (3) was identified as a new lead structure for H 4 R ligands. Exploration of the structure-activity relationship (SAR) of this scaffold led to the identification of 6,7-dichloro 3-(4-methylpiperazin-1-yl)quinoxalin-2(1H)-one (VUF 10214, 57) and 2-benzyl-3-(4-methyl-piperazin-1-yl)quinoxaline (VUF 10148, 20) as potent H 4 R ligands with nanomolar affinities. In vivo studies in the rat reveal that compound 57 has significant antiinflammatory properties in the carrageenan-induced paw-edema model

Identification and Characterization of Six Spectroscopically Confirmed Massive Protostructures at 2.5<z<4.52.5<z<4.5

We present six spectroscopically confirmed massive protostructures, spanning a redshift range of $2.5<z<4.5$ in the Extended Chandra Deep Field South (ECDFS) field discovered as part of the Charting Cluster Construction in VUDS and ORELSE (C3VO) survey. We identify and characterize these remarkable systems by applying an overdensity measurement technique on an extensive data compilation of public and proprietary spectroscopic and photometric observations in this highly studied extragalactic field. Each of these six protostructures, i.e., a large scale overdensity (volume $>9000$\thinspace cMpc$^3$) of more than $2.5\sigma_{\delta}$ above the field density levels at these redshifts, have a total mass $M_{tot}\ge10^{14.8}M_\odot$ and one or more highly overdense (overdensity$\thinspace>5\sigma_{\delta}$) peaks. One of the most complex protostructures discovered is a massive ($M_{tot}=10^{15.1}M_\odot$) system at $z\sim3.47$ that contains six peaks and 55 spectroscopic members. We also discover protostructures at $z\sim3.30$ and $z\sim3.70$ that appear to at least partially overlap on sky with the protostructure at $z\sim3.47$, suggesting a possible connection. We additionally report on the discovery of three massive protostructures at $z=2.67$, 2.80, and 4.14 and discuss their properties. Finally, we discuss the relationship between star formation rate and environment in the richest of these protostructures, finding an enhancement of star formation activity in the densest regions. The diversity of the protostructures reported here provide an opportunity to study the complex effects of dense environments on galaxy evolution over a large redshift range in the early universe.Comment: 10 pages, 4 figures, 1 tabl

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Sex differences in dementia risk and risk factors: Individual‐participant data analysis using 21 cohorts across six continents from the COSMIC consortium

Introduction: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno‐regional groups. Methods: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta‐analysis. Sex‐specific hazard ratios (HRs), and women‐to‐men ratio of hazard ratios (RHRs) for associations between RFs and all‐cause dementia were derived from mixed‐effect Cox models. Results: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low‐ and lower‐middle‐income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. Discussion: Dementia risk was higher in women than men, with possible variations by country‐level income settings, but most RFs appear to work similarly in women and men

Mar Menor: una laguna singular y sensible. Evaluación científica de su estado.

Este libro recopila las aportaciones que equipos de investigación de la Universidad de Murcia, Universidad Politécnica de Cartagena, Instituto Geológico-Minero de España, Universidad de Alicante, el Instituto Español de Oceanografía y otros organismos hicieron en las Jornadas Científicas del Mar Menor, celebradas en diciembre de 2014.La información recogida en este libro se estructura en dos grandes bloques, uno de Biología y Ecología del Mar Menor (capítulos 1 al 8) y otro de Condiciones fisicoquímicas e impacto de actividades humanas en la laguna (capítulos 9 al 14). El primer bloque resume buena parte de los estudios ecológicos realizados en el Mar Menor, que han servido para mejorar su conocimiento y también para cambiar antiguas asunciones sobre la naturaleza y el funcionamiento de estos ecosistemas lagunares (Capítulo 1). El segundo capítulo muestra que esta laguna alberga en zonas someras de su perímetro hábitats fundamentales para mantener y conservar tanto especies migratorias como residentes, que es necesario conocer para paliar el impacto de las actividades humanas que les afectan. En este sentido la reducción de la carga de nutrientes y contaminantes orgánicos e inorgánicos que fluyen hacia el Mar Menor puede ayudar a preservar la laguna en mejores condiciones, bien sea tratando las escorrentías (plantas de tratamiento, humedales artificiales u otras técnicas) y recuperar este agua para uso agrícola o evitar su descarga en la laguna (Capítulo 3). Estas actuaciones serán clave para la conservación de especies emblemáticas como el caballito de mar (Capítulo 4) y reducir el impacto de las proliferaciones masivas de medusas que se producen en la laguna desde 1993 (Capítulo 5). En este mismo sentido los cambios acaecidos en la laguna han favorecido la incursión de invertebrados marinos alóctonos (Capítulo 6) y han afectado a la respuesta de la dinámica poblacional de las aves acuáticas a distintas escalas (Capítulo 7). Para completar este bloque se ofrece una perspectiva histórica de la importancia que ha tenido la investigación sobre acuicultura realizada en esta laguna, que ha servido de base para su gran desarrollo actual (Capítulo 8). El segundo bloque se inicia con una evaluación del origen y evolución del Mar Menor desde el punto de vista geológico, y evidencia su vulnerabilidad ante el deterioro que puede sufrir la desaparición de la barrera de cierre y/o su colmatación (Capítulo 9). En el Capítulo 10 se describe la relevancia que tiene la interacción de los acuíferos del Campo de Cartagena con la laguna, que se produce no sólo a nivel superficial sino también subterráneo. Esta interacción permite el acceso de nutrientes a la laguna, a pesar de la cierta capacidad de depuración de los humedales que le circundan, y también de metales traza por los aportes de residuos mineros (Capítulo 11). De hecho los metales traza están presentes en los sedimentos de la laguna, y su distribución se ha caracterizado en la columna sedimentaria relacionándola con la granulometría y el contenido de materia orgánica del sedimento (Capítulo 12). Posteriormente se describe la entrada de diversos contaminantes orgánicos, incluyendo pesticidas y fármacos a través de la rambla del Albujón, y su distribución estacional en agua y sedimento de la laguna (Capítulo 13). Este segundo bloque finaliza con el Capítulo 14 en el que se describe la bioacumulación de hidrocarburos aromáticos policíclicos, pesticidas y fármacos en moluscos y peces del Mar Menor, así como los efectos biológicos que la carga contaminante que accede a través de la rambla del Albujón produce en los organismos que allí habitan. El libro concluye con un breve epílogo redactado por los editores de este libro