Publications by authors named "Laura Serra"

96 Publications

Association between early working life patterns, in publicly and privately owned companies, and the course of future sickness absence due to mental disorders: a cohort study in Catalonia (Spain).

BMJ Open 2021 Feb 16;11(2):e040480. Epub 2021 Feb 16.

CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Objectives: To assess the relationship between early working life patterns, at privately and publicly held companies, and the course of sickness absence (SA) due to mental disorders.

Methods: Cohort study of workers aged 18-28 years, affiliated with the Spanish social security system, living in Catalonia, who had at least one episode of SA due to mental disorders between 2012 and 2014. Individual prior working life trajectories were reconstructed through sequence analysis. Optimal matching analysis was performed to identify early working life patterns by clustering similar individual trajectories. SA trajectories were identified using latent class growth modelling analysis. Finally, the relationship between early working life patterns and subsequent SA trajectories was assessed via multinomial logistic regression models.

Results: Among both men and women, four labour market participation (LMP) patterns were identified: stable permanent employment (reference group), increasing permanent employment, fluctuating employment and delayed employment. Among women, an increasing permanent employment pattern in early working life was related to a decrease of accumulated SA days over time (adjusted OR (aOR) 2.08; 95% CI 1.18 to 3.66). In men, we observed a trend towards a middle stable accumulation of SA days in those with fluctuating employment (aOR 1.25, 95% CI 0.57 to 2.74) or delayed employment (aOR 1.79; 95% CI 0.59 to 5.41). In both men and women, an early working life in big companies was related to a more favourable SA trajectory.

Conclusions: Early LMP patterns characterised by an increasing stability-decreased number of transitions between temporary contracts and lack of social security coverage towards permanent contracts-were related to a better future SA course due to mental diagnosis.
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http://dx.doi.org/10.1136/bmjopen-2020-040480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888331PMC
February 2021

Lesion distribution and substrate of white matter damage in myotonic dystrophy type 1: Comparison with multiple sclerosis.

Neuroimage Clin 2021 14;29:102562. Epub 2021 Jan 14.

Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, United Kingdom; UOC Neurologia e Neurofisiopatologia, AO San Camillo Forlanini, Rome, Italy. Electronic address:

Myotonic Dystrophy type 1 (DM1) is an autosomal dominant condition caused by expansion of the CTG triplet repeats within the myotonic dystrophy protein of the kinase (DMPK) gene. The central nervous system is involved in the disease, with multiple symptoms including cognitive impairment. A typical feature of DM1 is the presence of widespread white matter (WM) lesions, whose total volume is associated with CTG triplet expansion. The aim of this study was to characterize the distribution and pathological substrate of these lesions as well as the normal appearing WM (NAWM) using quantitative magnetization transfer (qMT) MRI, and comparing data from DM1 patients with those from patients with multiple sclerosis (MS). Twenty-eight patients with DM1, 29 patients with relapsing-remitting MS, and 15 healthy controls had an MRI scan, including conventional and qMT imaging. The average pool size ratio (F), a proxy of myelination, was computed within lesions and NAWM for every participant. The lesion masks were warped into MNI space and lesion probability maps were obtained for each patient group. The lesion distribution, total lesion load and the tissue-specific mean F were compared between groups. The supratentorial distribution of lesions was similar in the 2 patient groups, although mean lesion volume was higher in MS than DM1. DM1 presented higher prevalence of anterior temporal lobe lesions, but none in the cerebellum and brainstem. Significantly reduced F values were found within DM1 lesions, suggesting a loss of myelin density. While F was reduced in the NAWM of MS patients, it did not differ between DM1 and controls. Our results provide further evidence for a need to compare histology and imaging using new MRI techniques in DM1 patients, in order to further our understanding of the underlying disease process contributing to WM disease.
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http://dx.doi.org/10.1016/j.nicl.2021.102562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848627PMC
January 2021

Hazelnut Allergy.

Medicina (Kaunas) 2021 Jan 14;57(1). Epub 2021 Jan 14.

Pediatric and Neonatology Unit, Imola Hospital, 40026 Imola, Italy.

Hazelnuts are frequently involved in IgE-mediated reactions and represent the main culprit of nut allergy in Europe. The clinical presentation varies from mild symptoms limited to the oropharynx [oral allergy syndrome (OAS)], due to the cross-reaction with homologues in pollen allergens and more severe events caused by the primary sensitization to highly stable molecules contained in hazelnuts. The aim of this review is to summarize the most relevant concepts in the field of hazelnut allergy and to provide a practical approach useful in the clinical practice References were identified by PubMed searches dating from January 2000 up to November 2020 using the search terms: "component resolved diagnosis" and "Hazelnut allergy. The storage proteins Cor a 9 and Cor a 14 resulted highly specific for primary hazelnut allergy and strongly associated with severe reactions, while the cross reactive Cor a 1, an homolog of the birch Bet v1, were related to OAS. Any cut-off has shown a specificity and sensitivity pattern as high as to replace the oral food challenge (OFC), which still remains the gold standard in the diagnosis of hazelnut allergy. To date there is still no definitive treatment. Hazelnut free-diet and treatment of symptoms with emergency management, including the prescription of auto-injective epinephrine, still represent the main approach. Oral allergen immunotherapy (AIT) appears a promising therapeutic strategy and the definition of individual clinical threshold would be useful for sensitized individuals, caregivers, and physicians to reduce social limitation, anxiety, and better manage food allergy. An accurate diagnostic work-up including clinical history, in vivo and in vitro test including component resolved diagnosis and OFC are essential to confirm the diagnosis, to assess the risk of a severe reaction, and to prescribe an adequate diet and treatment.
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http://dx.doi.org/10.3390/medicina57010067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828647PMC
January 2021

Association between the New COVID-19 Cases and Air Pollution with Meteorological Elements in Nine Counties of New York State.

Int J Environ Res Public Health 2020 12 4;17(23). Epub 2020 Dec 4.

Research Group on Statistics, Econometrics and Health (GRECS), University of Girona, 17003 Girona, Spain.

The principal objective of this article is to assess the possible association between the number of COVID-19 infected cases and the concentrations of fine particulate matter (PM) and ozone (O), atmospheric pollutants related to people's mobility in urban areas, taking also into account the effect of meteorological conditions. We fit a generalized linear mixed model which includes spatial and temporal terms in order to detect the effect of the meteorological elements and COVID-19 infected cases on the pollutant concentrations. We consider nine counties of the state of New York which registered the highest number of COVID-19 infected cases. We implemented a Bayesian method using integrated nested Laplace approximation (INLA) with a stochastic partial differential equation (SPDE). The results emphasize that all the components used in designing the model contribute to improving the predicted values and can be included in designing similar real-world data (RWD) models. We found only a weak association between PM and ozone concentrations with COVID-19 infected cases. Records of COVID-19 infected cases and other covariates data from March to May 2020 were collected from electronic health records (EHRs) and standard RWD sources.
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http://dx.doi.org/10.3390/ijerph17239055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729491PMC
December 2020

Automatic multispectral MRI segmentation of human hippocampal subfields: an evaluation of multicentric test-retest reproducibility.

Brain Struct Funct 2021 Jan 24;226(1):137-150. Epub 2020 Nov 24.

Center for Mind/Brain Sciences (CIMeC), University of Trento, Rovereto, Italy.

Accurate and reproducible automated segmentation of human hippocampal subfields is of interest to study their roles in cognitive functions and disease processes. Multispectral structural MRI methods have been proposed to improve automated hippocampal subfield segmentation accuracy, but the reproducibility in a multicentric setting is, to date, not well characterized. Here, we assessed test-retest reproducibility of FreeSurfer 6.0 hippocampal subfield segmentations using multispectral MRI analysis pipelines (22 healthy subjects scanned twice, a week apart, at four 3T MRI sites). The harmonized MRI protocol included two 3D-T1, a 3D-FLAIR, and a high-resolution 2D-T2. After within-session T1 averaging, subfield volumes were segmented using three pipelines with different multispectral data: two longitudinal ("long_T1s" and "long_T1s_FLAIR") and one cross-sectional ("long_T1s_FLAIR_crossT2"). Volume reproducibility was quantified in magnitude (reproducibility error-RE) and space (DICE coefficient). RE was lower in all hippocampal subfields, except for hippocampal fissure, using the longitudinal pipelines compared to long_T1s_FLAIR_crossT2 (average RE reduction of 0.4-3.6%). Similarly, the longitudinal pipelines showed a higher spatial reproducibility (1.1-7.8% of DICE improvement) in all hippocampal structures compared to long_T1s_FLAIR_crossT2. Moreover, long_T1s_FLAIR provided a small but significant RE improvement in comparison to long_T1s (p = 0.015), whereas no significant DICE differences were found. In addition, structures with volumes larger than 200 mm had better RE (1-2%) and DICE (0.7-0.95) than smaller structures. In summary, our study suggests that the most reproducible hippocampal subfield FreeSurfer segmentations are derived from a longitudinal pipeline using 3D-T1s and 3D-FLAIR. Adapting a longitudinal pipeline to include high-resolution 2D-T2 may lead to further improvements.
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http://dx.doi.org/10.1007/s00429-020-02172-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817563PMC
January 2021

Correction to: Sickness absence trajectories following labour market participation patterns: a cohort study in Catalonia (Spain), 2012-2014.

BMC Public Health 2020 Oct 1;20(1):1493. Epub 2020 Oct 1.

Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12889-020-09544-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530968PMC
October 2020

Sickness absence trajectories following labour market participation patterns: a cohort study in Catalonia (Spain), 2012-2014.

BMC Public Health 2020 Aug 27;20(1):1306. Epub 2020 Aug 27.

Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.

Background: Previous studies have focused on the relationship between employment pathways and health-related outcomes based on cross-sectional or longitudinal approaches. However, little is known about the cumulative effects of employment status mobility on sickness absence (SA) over time. The aim of the present study was to examine the association between prior labour market participation (LMP) patterns and SA trajectories from a life-course perspective.

Methods: This cohort study was based on a sample of 11,968 salaried workers living in Catalonia and affiliated with the Spanish Social Security system, who accumulated more than 15 days on SA in at least one quarter during 2012-2014. Individuals were grouped into three different working life stages: early (18-25 years), middle (26-35 years), and late (36-45 years). To identify LMP patterns, we applied sequence analysis and cluster analysis (2002-2011), and we used latent class growth modelling to identify SA trajectories (2012-2014). Finally, we applied multinomial logistic regression models to assess the relationship between LMP patterns and SA trajectories.

Results: The analyses yielded six LMP patterns: stable employment (value range: 63-81%), increasing employment (5-22%), without long-term coverage (7-8%), decreasing employment (4-10%), fluctuant employment (13-14%), and steeply decreasing employment (7-9%). We also identified four SA trajectories: low stable (83-88%), decreasing (5-9%), increasing (5-11%), and high stable (7-16%). However, the only significant association we identified for LMP patterns and SA trajectories was among young men, for whom an increasing employment pattern was significantly associated with a lower risk for increased days on SA (adjusted odds ratio: 0.21; 95% confidence interval: 0.05-0.96).

Conclusions: SA trajectories are generally not related to prior 10-year LMP patterns at any stage of working life. To disentangle this relationship, future research might benefit from considering working life transitions with a quality-of-work approach framed with contextual factors closer to the SA course.
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http://dx.doi.org/10.1186/s12889-020-09396-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453716PMC
August 2020

Do birthrates contribute to sickness absence differences in women? A cohort study in Catalonia, Spain, 2012-2014.

PLoS One 2020 26;15(8):e0237794. Epub 2020 Aug 26.

Research Group on Statistics, Econometrics and Health (GRECS), University of Girona, Girona, Spain.

Aims: This study explores the differences in sickness absence trends in women according to reproductive age group and medical diagnoses.

Methods: Data were obtained from two administrative registries: the Continuous Working Life Sample and the Catalonian Institute of Medical Evaluations from 2012 to 2014, containing 47,879 female employees. Incidence rates and incidence risk ratios derived from Poisson and negative binomial models were calculated to compare sickness absence trends among reproductive age groups based on Catalonian birthrates: early-reproductive (25-34 years old), middle-reproductive (35-44) and late-reproductive (45-54), according to diagnostic groups, selected diseases, type of contract, occupational category, and country of origin.

Results: Younger women show a higher incidence of overall sickness absence compared to late-reproductive-aged women. Incidence risk ratios of sickness absence decreased significantly from early-reproductive to late-reproductive age for low back pain, hemorrhage in early pregnancy, nausea and vomiting, and abdominal and pelvic pain.

Discussion: The higher incidence of sickness absence due to pregnancy-related health conditions in early-reproductive women compared to other reproductive age groups, may explain the sickness absence differences by age in women. Proper management of sickness absence related to pregnancy should be a goal to reduce the sickness absence gap between younger and older women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237794PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449461PMC
October 2020

Behavioral psychological symptoms of dementia and functional connectivity changes: a network-based study.

Neurobiol Aging 2020 10 16;94:196-206. Epub 2020 Jun 16.

Department of Neuroscience, Brighton & Sussex Medical School, University of Sussex, Brithon, UK; Department of Neuroscience "Rita Levi Montalcini", University of Torino, Turin, Italy.

Behavioral and psychological symptoms of dementia (BPSD) are commonly observed since the early stage of Alzheimer's disease (AD) associated with structural brain changes. It is conceivable that they may also relate to functional brain changes. This resting-state functional MRI (RS-fMRI) study investigated the alterations within functional brain networks of a cohort of AD patients at different clinical stages who presented with BPSD. One hundred one AD patients and 56 patients with amnestic mild cognitive impairment underwent a neuropsychological evaluation including the Neuropsychiatry Inventory-12 (NPI-12). All patients and 35 healthy controls (HS) underwent 3T-MRI. Factor analysis was used to extract the principal factors from NPI-12, while RS-fMRI data were processed using graph theory to investigate functional connectivity. Five factors were extracted from NPI-12. Sixty-two percent of patients showed BPSD and functional brain connectivity changes in various networks compared to those without BPSD and HS. These changes contributed to account for patients' BPSD. This work opens new perspectives in terms of nonpharmacological interventions that might be designed to modulate brain connectivity and improve patients' BPSD.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.06.009DOI Listing
October 2020

Ventral tegmental area dysfunction affects decision-making in patients with myotonic dystrophy type-1.

Cortex 2020 07 8;128:192-202. Epub 2020 Apr 8.

Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy; Department of Neuroscience, Brighton & Sussex Medical School, University of Sussex, Brighton, East Sussex, United Kingdom. Electronic address:

The clinical manifestations of Myotonic Dystrophy type-1 (DM1) are associated with a complex mixture of multisystem features including cognitive dysfunctions that strongly impact on patients' social and occupational functioning. Decision making, a function controlled by dopaminergic circuitry, is critical for succeeding in one's social and professional life. We tested here the hypothesis that altered connectivity of the ventral tegmental area (VTA), one of the major sources of diffuse dopaminergic projections in the brain, might account for some higher-level dysfunctions observed in patients with DM1. In this case-control study, we recruited 31 patients with DM1 and 26 healthy controls who underwent the IOWA Gambling task and resting-state functional MRI (RS-fMRI) at 3T. Functional connectivity of the VTA was assessed using RS-fMRI. VTA connectivity was compared between 25 DM1 patients and all the controls, and the presence of associations between VTA connectivity and IOWA Gambling task performance was also investigated. DM1 patients performed significantly worse than controls at the IOWA Gambling task. A significant increase of functional connectivity was observed between VTA and the left supramarginal and superior temporal gyri in DM1 patients. Patients' IOWA Gambling task net-scores were strictly associated with VTA-driven functional connectivity in the bilateral supplementary motor area and right precentral gyrus. This study demonstrates a prominent deficit of decision-making in patients with DM1. It might be related to increased connectivity between VTA and brain areas critically involved in the reward/punishment system and social cognition. These findings indicate that dopaminergic function is a potential target for pharmacological and non-pharmacological interventions in DM1.
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http://dx.doi.org/10.1016/j.cortex.2020.03.022DOI Listing
July 2020

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1.

Front Neurol 2020 28;11:113. Epub 2020 Feb 28.

Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

To investigate the cortical thickness in myotonic dystrophy type 1 (DM1) and its potential association with patients' genetic triplet expansion and social cognition deficits. Thirty patients with DM1 underwent the Social Cognition Battery Test and magnetic resonance imaging (MRI) scanning at 3 T. Twenty-five healthy subjects (HSs) were enrolled in the study to serve as a control group for structural MRI data. To assess changes in cortical thickness in DM1 patients, they were compared to HSs using a -test model. Correlations were used to assess potential associations between genetic and clinical characteristics and social cognition performances in the patient group. Additionally, multiple regression models were used to explore associations between cortical thickness, CTG triplet expansion size, and scores obtained by DM1 patients on the Social Cognition Battery. DM1 patients showed low performances in several subtests of the Social Cognition Battery. Specifically, they obtained pathological scores at Emotion Attribution Test (i.e., Sadness, Embarrassment, Happiness, and Anger) and at the Social Situations Test (i.e., recognition of normal situation, recognition of aberrant behavior). Significant negative correlations were found between CTG triplet expansion size and Embarrassment, and Severity of Aberrant Behavior. Similarly, a negative correlation was found between patients' MIRS scores and Sadness. DM1 patients compared to HSs showed reduced thickness in the right premotor cortex, angular gyrus, precuneus, and inferior parietal lobule. Significant associations were found between patients' CTG triplet expansion size and thickness in left postcentral gyrus and in the left primary somatosensory cortex, in the posterior cingulate cortex bilaterally, and in the right lingual gyrus. Finally, significant associations were found between cortical thickness and sadness in the superior temporal gyrus, the right precentral gyrus, the right angular gyrus, and the left medial frontal gyrus bilaterally. DM1 patients showed a negative correlation between cortical thickness in the bilateral precuneus and in the left lateral occipital cortex and performance at the Social Situations Test. Finally, DM1 patients showed a negative correlation between cortical thickness in the left precuneus and in the superior frontal gyrus and scores at the Moral Distinction Test. The present study shows both cortical thickness changes in DM1 patients compared to controls and significant associations between cortical thickness and patients' social cognition performances. These data confirm the presence of widespread brain damages associated with cognitive impairment in DM1 patients.
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http://dx.doi.org/10.3389/fneur.2020.00113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059122PMC
February 2020

Cerebellar dentate nucleus functional connectivity with cerebral cortex in Alzheimer's disease and memory: a seed-based approach.

Neurobiol Aging 2020 05 15;89:32-40. Epub 2020 Jan 15.

Neuroimaging Laboratory, Fondazione Santa Lucia-IRCCS, Rome, Italy; Clinical Imaging Sciences Center, Brighton and Sussex Medical School, Brighton, UK.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by specific patterns of gray and white matter damage and cognitive/behavioral manifestations. The cerebellum has also been implicated in the pathophysiology of AD. Because the cerebellum is known to have strong functional connectivity (FC) with associative cerebral cortex regions, it is possible to hypothesize that it is incorporated into intrinsic FC networks relevant to cognitive manifestation of AD. In the present study, the cerebellar dentate nucleus, the largest cerebellar nucleus and the major output channel to the cerebral cortex, was chosen as the region of interest to test potential cerebellocerebral FC alterations and correlations with patients' memory impairment in a group of patients with AD. Compared to controls, patients with AD showed an increase in FC between the dentate nucleus and regions of the lateral temporal lobe. This study demonstrates that lower memory performances in AD may be related to altered FC within specific cerebellocortical functional modules, thus suggesting the cerebellar contribution to AD pathophysiology and typical memory dysfunctions.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.10.026DOI Listing
May 2020

Cerebellar White Matter Disruption in Alzheimer's Disease Patients: A Diffusion Tensor Imaging Study.

J Alzheimers Dis 2020 ;74(2):615-624

Neuroimaging Laboratory, Fondazione Santa Lucia, IRCCS, Rome, Italy.

The cognitive role of the cerebellum has recently gained much attention, and its pivotal role in Alzheimer's disease (AD) has now been widely recognized. Diffusion tensor imaging (DTI) has been used to evaluate the disruption of the microstructural milieu in AD, and though several white matter (WM) tracts such as corpus callosum, inferior and superior longitudinal fasciculus, cingulum, fornix, and uncinate fasciculus have been evaluated in AD, data on cerebellar WM tracts are currently lacking. We performed a tractography-based DTI reconstruction of the middle cerebellar peduncle (MCP), and the left and right superior cerebellar peduncles separately (SCPL and SCPR) and addressed the differences in fractional anisotropy (FA), axial diffusivity (Dax), radial diffusivity (RD), and mean diffusivity (MD) in the three tracts between 50 patients with AD and 25 healthy subjects. We found that AD patients showed a lower FA and a higher RD compared to healthy subjects in MCP, SCPL, and SCPR. Moreover, higher MD was found in SCPR and SCPL and higher Dax in SCPL. This result is important as it challenges the traditional view that WM bundles in the cerebellum are unaffected in AD and might identify new targets for therapeutic interventions.
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http://dx.doi.org/10.3233/JAD-191125DOI Listing
January 2020

Default Mode Network structural alterations in Kocher-Monro trajectory white matter transection: A 3 and 7 tesla simulation modeling approach.

PLoS One 2019 7;14(11):e0224598. Epub 2019 Nov 7.

Laboratory of Surgical Neuroanatomy, University of Barcelona, Barcelona, Spain.

The Kocher-Monro trajectory to the cerebral ventricular system represents one of the most common surgical procedures in the field of neurosurgery. Several studies have analyzed the specific white matter disruption produced during this intervention, which has no reported adverse neurological outcomes. In this study, a graph-theoretical approach was applied to quantify the structural alterations in whole-brain level connectivity. To this end, 132 subjects were randomly selected from the Human Connectome Project dataset and used to create 3 independent 44 subjects groups. Two of the groups underwent a simulated left/right Kocher-Monro trajectory and the third was kept as a control group. For the right Kocher-Monro approach, the nodal analysis revealed decreased strength in the anterior cingulate gyrus of the transected hemisphere. The network-based statistic analysis revealed a set of right lateralized subnetworks with decreased connectivity strength that is consistent with a subset of the Default Mode Network, Salience Network, and Cingulo-Opercular Network. These findings could allow for a better understanding of structural alterations caused by Kocher-Monro approaches that could reveal previously undetected clinical alterations and inform the process of designing safer and less invasive cerebral ventricular approaches.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224598PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837312PMC
March 2020

Testing for the Myth of Cognitive Reserve: Are the Static and Dynamic Cognitive Reserve Indexes a Representation of Different Reserve Warehouses?

J Alzheimers Dis 2019 ;72(1):111-126

Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.

Background: Cognitive reserve (CR) explains the individual resilience to neurodegeneration. Years of formal education express the static measure of reserve (sCR). A dynamic aspect of CR (dCR) has been recently proposed.

Objective: The aim of the study was to compare sCR and dCR indexes, respectively, to detect brain abnormalities in Alzheimer's disease (AD) patients.

Methods: 117 individuals [39 AD, 40 amnestic mild cognitive impairment (aMCI), 38 healthy subjects (HS)] underwent neuropsychological evaluation and a 3T-MRI. T1-weighted volumes were used for manual segmentation of the hippocampus and of the parahippocampal cortices. Years of formal education were used as an index of sCR. Partial Least Square analysis was used to decompose the variance of individual MMSE scores, considered as a dCR index. In aMCI and AD patients, the brain abnormalities have been assessed comparing individuals with high and low levels of sCR and dCR in turn. Moreover, we investigated the effect of the different CR indexes in mediating the relationship between changes in brain volumes and memory performances.

Results: sCR and dCR indexes classified differently individuals having high or low levels of CR. Smaller hippocampal and parahippocampal volumes in high dCR patients were found. The sCR and dCR indexes mediated significantly the relationship between brain abnormalities and memory in patients.

Conclusions: CR mediated the relationship between brain and memory dysfunctions. We hypothesized that sCR and dCR indexes are a representation of different warehouses of reserve not operating in parallel but forming a complex system, in which crystalized cognitive abilities and actual cognitive efficiency interact with brain atrophy impacting on memory.
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http://dx.doi.org/10.3233/JAD-190716DOI Listing
November 2020

Component-Resolved Diagnosis in Food Allergies.

Medicina (Kaunas) 2019 Aug 18;55(8). Epub 2019 Aug 18.

Pediatric and Neonatology Unit, Imola Hospital, 40026 Imola, Italy.

Component-resolved diagnostics (CRD) in food allergies is an approach utilized to characterize the molecular components of each allergen involved in a specific IgE (sIgE)-mediated response. In the clinical practice, CRD can improve diagnostic accuracy and assist the physician in many aspects of the allergy work-up. CRD allows for discriminatory co-sensitization versus cross-sensitization phenomena and can be useful to stratify the clinical risk associated with a specific sensitization pattern, in addition to the oral food challenge (OFC). Despite this, there are still some unmet needs, such as the risk of over-prescribing unnecessary elimination diets and adrenaline auto-injectors. Moreover, up until now, none of the identified sIgE cutoff have shown a specificity and sensitivity profile as accurate as the OFC, which is the gold standard in diagnosing food allergies. In light of this, the aim of this review is to summarize the most relevant concepts in the field of CRD in food allergy and to provide a practical approach useful in clinical practice.
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http://dx.doi.org/10.3390/medicina55080498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723663PMC
August 2019

Trajectories of sickness absence among salaried workers: evidence from the WORKss cohort in Catalonia (Spain), 2012-2014.

BMJ Open 2019 07 3;9(7):e029092. Epub 2019 Jul 3.

Department of Experimental and Health Sciences, Centre for Research in Occupational Health (CiSAL), Pompeu Fabra University, Barcelona, Spain.

Objectives: Sickness absence (SA) is a widely studied integrated measure of health status. To better understand how SA behaves over time (SA trajectory) a longitudinal and individual-centred approach will allow identifying groups of individuals who share common characteristics. The aim of this study was to identify and describe SA trajectories and to assess employment conditions and diagnosis groups as determinants.

Setting: Working-life and sickness absence administrative records from a representative sample of affiliated with the Spanish Social Security system.

Participants: 38 420 workers affiliated with the Spanish Social Security system, born 1949 to 1969 or 1970 to 1990, resident in Catalonia who had SA between 2012 and 2014 (75 212 episodes).

Results: We identified three different SA trajectories in both birth cohorts for men and women: low-stable (86.2% to 90.8% of individuals), decreasing (4.4% to 5.9% of individuals) and increasing (4.1% to 8.7% of individuals) accumulated days of SA. The main characteristic of SA trajectories was the medical diagnosis group. The increasing SA trajectory had a higher proportion of workers with SA due to mental disorders compared with the other trajectories. The association analysis showed diagnosis group strongly related with all SA trajectories, particularly SA due to mental disorders showed the strongest association with the increasing trajectory among young men (adjusted OR (aOR): 42.40, 95% CI 17.03 to 105.57). Low salary levels exhibited a strong relationship with decreased accumulation of SA days over time for old women (aOR: 2.08, 95% CI 1.36 to 3.18) and men (aOR: 2.75, 95% CI 1.77 to 4.27). Unskilled manual occupations were associated with increasing trajectories among young women (aOR: 1.36, 95% CI 1.01 to 1.84). No significant differences were observed for other employment conditions across trajectories.

Conclusions: Workers with mental disorders are more likely to have increased days of SA, whereas low salary levels at later ages are related to a decrease in SA days over time. Special attention to preventing the course of mental disorders at young and middle age is warranted.
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http://dx.doi.org/10.1136/bmjopen-2019-029092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615827PMC
July 2019

Thalamocortical disconnection affects the somatic marker and social cognition: a case report.

Neurocase 2019 Feb - Apr;25(1-2):1-9. Epub 2019 Mar 31.

a Neuroimaging Laboratory , Santa Lucia Foundation, IRCCS , Rome , Italy.

Thalamo-cortical connectivity was characterised in a patient with bilateral infarct of the thalami, without evidence of cognitive deficits in everyday life. Patient underwent social and emotional tests, Iowa Gambling Task (IGT), with and without concomitant heart rate variability (HRV) recording and at 3T-MRI to assess thalamo-cortical connectivity. Patient showed impairment at the IGT, in somatic marker, in emotions and theory of mind. MRI documented a bilateral damage of the centromedian-parafascicular complex. Patient's thalamic lesions disconnected brain areas involved in decision-making and autonomic regulation, affecting the somatic marker and resulting in the neuropsychological deficit exhibited by L.C.
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http://dx.doi.org/10.1080/13554794.2019.1599025DOI Listing
December 2019

Ventral tegmental area disruption in Alzheimer's disease.

Aging (Albany NY) 2019 03;11(5):1325-1326

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

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http://dx.doi.org/10.18632/aging.101852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428109PMC
March 2019

What good is the reserve? A translational perspective for the managing of cognitive decline.

Neural Regen Res 2019 Jul;14(7):1219-1220

Department of Clinical and Behavioural Neurology, IRCCS Fondazione Santa Lucia; Department of Human Sciences, Guglielmo Marconi University, Rome, Italy.

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http://dx.doi.org/10.4103/1673-5374.251328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425844PMC
July 2019

Working conditions and absence from work during pregnancy in a cohort of healthcare workers.

Occup Environ Med 2019 04 23;76(4):236-242. Epub 2019 Jan 23.

Center for Research in Occupational Health, IMIM - Hospital del Mar Medical Research Institute, University Pompeu Fabra, Barcelona, Spain.

Objectives: To assess the relationship between exposure to occupational risk factors during pregnancy and absence from work using two different social benefits.

Method: Three working pregnancy trajectories (WPT) were identified in a cohort of 428 pregnant workers from a healthcare institution (period 2010-2014), based on absence days and using cluster analysis. WPT1 included absences mainly covered by sickness absence benefit (32.0% of women), WPT2 included absences covered by pregnancy occupational risk (POR) benefit (28.3%) and WPT3 were pregnant workers with few absences (39.9%). Exposure to occupational risk factors was assessed by experts and association with trajectories was analysed using logistic regression. Relative risks (RR) and their 95% CIs were adjusted for age, type of contract and shift work.

Results: WPT2 was associated with exposure to physical (RR=1.86, 95%CI 1.17 to 2.97), safety (RR=2.10, 95%CI 1.61 to 2.73), ergonomic (RR=2.52, 95%CI 1.89 to 3.36) and psychosocial (RR=1.79, 95%CI 1.31 to 2.46) factors, and with exposure level. For physicians, WPT1 was associated with safety risks (RR=3.13, 95%CI 1.22 to 7.99), WPT2 with chemical and ergonomic for administrative/technical support (RR=12.20, 95%CI 1.69 to 88.09; RR=14.09, 95%CI 1.34 to 148.61, respectively), with safety and ergonomic risks for nursing aides (RR=1.84, 95%CI 1.12 to 3.02; RR=3.94, 95% CI 2.38 to 6.53, respectively), and with physical (RR=1.72, 95%CI 1.04 to 2.86), safety (RR=2.21, 95%CI 1.62 to 3.03), ergonomic (RR=2.02, 95%CI 1.44 to 2.86) and psychosocial factors (RR=1.96, 95%CI 1.32 to 2.90) for nurses.

Conclusions: Absences from work covered by POR benefit show a consistent relationship with exposure to occupational risks. Sickness absence is the most frequent benefit used by pregnant workers. Current social benefits are apparently used adequately for protecting women from occupational exposures. Future studies are needed to clarify this further.
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http://dx.doi.org/10.1136/oemed-2018-105369DOI Listing
April 2019

Patterns of Cerebellar Gray Matter Atrophy Across Alzheimer's Disease Progression.

Front Cell Neurosci 2018 20;12:430. Epub 2018 Nov 20.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

The role of the cerebellum in cognitive function has been broadly investigated in the last decades from an anatomical, clinical, and functional point of view and new evidence points toward a significant contribution of the posterior lobes of the cerebellum in cognition in Alzheimer's disease (AD). In the present work we used SUIT-VBM (spatially unbiased infratentorial template, voxel-based morphometry) to perform an analysis of the pattern of cerebellar gray matter (GM) atrophy in amnestic mild cognitive impairment (a-MCI) and AD dementia patients compared to healthy subjects (HS), in order to follow the changes of non-motor features of cerebellar degeneration throughout disease progression. This template has been validated to guarantee a significant improvement in voxel-to-voxel alignment of the individual fissures and the deep cerebellar nuclei compared to Montreal Neurological Institute (MNI) whole-brain template. Our analysis shows a progression of cerebellar GM volume changes throughout a continuous spectrum from early to late clinical stages of AD. In particular vermis and paravermian areas of the anterior (I-V) and posterior (VI) lobes are involved since the a-MCI stage, with a later involvement of the hemispheric part of the posterior lobes (VI lobule) and Crus I in AD dementia patients only. These findings support the role of the cerebellum in higher-level functions, and whilst confirming previous data on the involvement of Crus I in AD dementia, provide new evidence of an involvement of the vermis in the early stages of the disease.
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http://dx.doi.org/10.3389/fncel.2018.00430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255820PMC
November 2018

The role of hippocampus in the retrieval of autobiographical memories in patients with amnestic Mild Cognitive Impairment due to Alzheimer's disease.

J Neuropsychol 2020 03 19;14(1):46-68. Epub 2018 Nov 19.

Department of Clinical and Behavioural Neurology, Santa Lucia Foundation, IRCCS, Rome, Italy.

The role of the hippocampus and neocortical areas in the retrieval of past memories in pre-dementia Alzheimer's disease (AD) patients was investigated. The aim was to assess whether the hippocampus has a temporary role in memory trace formation, according to the Cortical Reallocation Theory (CRT), or whether it continuously updates and enriches memories, according to the Multiple Trace Theory. According to the former theory, hippocampal damage should affect more recent memories, whereas the association cortex is expected to affect memories of the entire lifespan. In the second case, damage to either the hippocampus or the association cortices should affect memories of the entire lifespan. Seventeen patients with amnestic Mild Cognitive Impairment due to AD were submitted to autobiographical (i.e., episodic and semantic personal) memory assessment. Patients underwent MRI for the acquisition of T1-weighted brain volumes. Voxel-based morphometry was used to assess correlations between grey matter (GM) volumes and autobiographical memory. Correlation analyses revealed a strict association between GM volumes in the hippocampus and patients' ability to retrieve the most recent but not the oldest autobiographical memories in both aspects, episodic and semantic. Moreover, patients' GM volumes in the pre-frontal and temporal polar areas were associated with recollection of episodic and semantic events, respectively. Finally, GM volumes in the precuneus and occipital cortex were associated with retrieval of the most recent episodic events. These findings indicate that the hippocampus has a specific time-dependent role; thus, they support the CRT.
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http://dx.doi.org/10.1111/jnp.12174DOI Listing
March 2020

In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease.

Neurobiol Aging 2018 12 23;72:72-82. Epub 2018 Aug 23.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Neuroscience, Brighton & Sussex Medical School, University of Sussex, Brighton, East Sussex, United Kingdom. Electronic address:

We assessed here functional connectivity changes in the locus coeruleus (LC) and ventral tegmental area (VTA) of patients with Alzheimer's disease (AD). We recruited 169 patients with either AD or amnestic mild cognitive impairment due to AD and 37 elderly controls who underwent cognitive and neuropsychiatric assessments and resting-state functional magnetic resonance imaging at 3T. Connectivity was assessed between LC and VTA and the rest of the brain. In amnestic mild cognitive impairment patients, VTA disconnection was predominant with parietal regions, while in AD patients, it involved the posterior nodes of the default-mode network. We also looked at the association between neuropsychiatric symptoms (assessed by the neuropsychiatric inventory) and VTA connectivity. Symptoms such as agitation, irritability, and disinhibition were associated with VTA connectivity with the parahippocampal gyrus and cerebellar vermis, while sleep and eating disorders were associated with VTA connectivity to the striatum and the insular cortex. This suggests a contribution of VTA degeneration to AD pathophysiology and to the occurrence of neuropsychiatric symptoms. We did not find evidence of LC disconnection, but this could be explained by the size of this nucleus, which makes it difficult to isolate. These results are consistent with animal findings and have potential implications for AD prognosis and therapies.
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.08.012DOI Listing
December 2018

Rethinking the Reserve with a Translational Approach: Novel Ideas on the Construct and the Interventions.

J Alzheimers Dis 2018 ;65(4):1065-1078

Department of Clinical and Behavioural Neurology, IRCCS Fondazione Santa Lucia, Rome, Italy.

The concept of brain, cognitive, and neural reserves has been introduced to account for the apparent discrepancies between neurological damage and clinical manifestations. However, these ideas are yet theoretical suggestions that are not completely assimilated in the clinical routine. The mechanisms of the reserves have been extensively studied in neurodegenerative pathologies, in particular in Alzheimer's disease. Both human and animal studies addressed this topic by following two parallel pathways. The specific aim of the present review is to attempt to combine the suggestions derived from the two different research fields to deepen the knowledge about reserves. In fact, the achievement of a comprehensive theoretical framework on reserve mechanisms is an essential step to propose well-timed interventions tailored to the clinical characteristics of patients. The present review highlights the importance of addressing three main aspects: the definition of reserve proxy measures, the interaction between reserve level and therapeutic interventions, and the specific time-window of reserve efficacy.
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http://dx.doi.org/10.3233/JAD-180609DOI Listing
August 2019

CSF β-amyloid predicts prognosis in patients with multiple sclerosis.

Mult Scler 2019 08 7;25(9):1223-1231. Epub 2018 Aug 7.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy/University of Milan, Dino Ferrari Center, Milan, Italy.

Background: The importance of predicting disease progression in multiple sclerosis (MS) has increasingly been recognized, and hence reliable biomarkers are needed.

Objectives: To investigate the prognostic role of cerebrospinal fluid (CSF) amyloid beta (Aβ) levels by the determination of a cut-off value to classify patients in slow and fast progressors. To evaluate possible association with white matter (WM) and grey matter (GM) damage at early disease stages.

Methods: Sixty patients were recruited and followed up for 3-5 years. Patients underwent clinical assessment, brain magnetic resonance imaging (MRI; at baseline and after 1 year), and CSF analysis to determine Aβ levels. T1-weighted volumes were calculated. T2-weighted scans were used to quantify WM lesion loads.

Results: Lower CSF Aβ levels were observed in patients with a worse follow-up Expanded Disability Status Scale (EDSS;  = -0.65,  < 0.001). The multiple regression analysis confirmed CSF Aβ concentration as a predictor of patients' EDSS increase ( = -0.59,  < 0.0001). Generating a receiver operating characteristic curve, a cut-off value of 813 pg/mL was determined as the threshold able to identify patients with worse prognosis (95% confidence interval (CI): 0.690-0.933,  = 0.0001). No differences in CSF tau and neurofilament light chain (NfL) levels were observed ( > 0.05).

Conclusion: Low CSF Aβ levels may represent a predictive biomarker of disease progression in MS.
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http://dx.doi.org/10.1177/1352458518791709DOI Listing
August 2019

[Occupational risk during pregnancy and sick leave in a cohort of workers from Parc de Salut Mar (Barcelona, Spain)].

Gac Sanit 2019 Sep - Oct;33(5):455-461. Epub 2018 Jun 15.

Servicio de Salud Laboral, Parc de Salut Mar, IMIM PSMar, Barcelona, España; Centro de Investigación en Salud Laboral, Universitat Pompeu Fabra, Barcelona, España; CIBER de Epidemiología y Salud Pública (CIBERESP), España. Electronic address:

Objective: To study the use of the Pregnancy occupational risk benefit (PORB) and non-work related sickness absence (NWSA) in a cohort of pregnant workers of Parc de Salut Mar, Barcelona (Spain).

Method: Retrospective cohort study of 428 pregnant workers between 2010 and 2014, who were followed-up until delivery. Absences from work, both PORB and NWSA were recorded until the beginning of their maternity leave. The sequence analysis identifies four trajectories, which are described according to workers demographic and job characteristics.

Results: Of the total cohort, 56 (13.1%) accessed only the PORB, representing 6.126 days of absence; 68 (15.9%) also accessed PORB, with 7.127 days of absence, but had previously accumulated 102 episodes of NWSA with 1.820 days of absence. The majority of pregnant workers in the sample (69.9%) took only one or several episodes of NWSA without using PORB, with 545 episodes and 26,337 days of absence. Most were active during the first quarter and it is from the second quarter that episodes of long-term NWSA appeared. During the last month of pregnancy more than 80% of the workers were absent from work.

Conclusions: Pregnant workers remained at work for two thirds of their pregnancy. Absences were mainly due to episodes of NWSA. PORB represented one third of them. As in other similar countries, our results suggest a change in the management of social protection benefits for pregnant workers.
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http://dx.doi.org/10.1016/j.gaceta.2018.03.003DOI Listing
February 2020

Quantitative Magnetization Transfer of White Matter Tracts Correlates with Diffusion Tensor Imaging Indices in Predicting the Conversion from Mild Cognitive Impairment to Alzheimer's Disease.

J Alzheimers Dis 2018 ;63(2):561-575

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome.

Patients with amnestic mild cognitive impairment (aMCI) have higher probability to develop Alzheimer's disease (AD) than elderly controls. The detection of subtle changes in brain structure associated with disease progression and the development of tools to identify patients at high risk for dementia in a short time is crucial. Here, we used probabilistic white matter (WM) tractography to explore microstructural alterations within the main association, limbic, and commissural pathways in aMCI patients who converted to AD after 1 year follow-up (MCIconverters) and those who remained stable (MCIstable). Both diffusion tensor imaging (DTI) and quantitative magnetization transfer (qMT) parameters have been considered for a comprehensive pathophysiological characterization of the WM damage. Overall, tract-specific parameters derived from qMT and DTI at baseline were able to differentiate aMCI patients who converted to AD from those who remained stable in time. In particular, the qMT exchange rate, RMB0, of the right uncinate fasciculus was significantly decreased in MCIconverters, whereas fractional anisotropy was significantly decreased in the bilateral superior cingulum in MCIconverters compared to MCIstable. These results confirm the involvement of WM and particularly of association fibers in the progression of AD, highlighting disconnection as a potential mechanism.
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http://dx.doi.org/10.3233/JAD-170995DOI Listing
June 2019

Ventral Tegmental Area in Prodromal Alzheimer's Disease: Bridging the Gap between Mice and Humans.

J Alzheimers Dis 2018 ;63(1):181-183

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

Alzheimer's disease (AD) is a progressive neurological disorder characterized by several cognitive and non-cognitive symptoms, with episodic memory being the earliest and most prominently impaired cognitive function. Dopaminergic signals are required for encoding hippocampal memory for new events and the ventral tegmental area (VTA), together with the locus coeruleus, are the primary sources of dopamine acting on dopaminergic receptors in the hippocampus. With this in mind, a recent study on a validated mouse model of AD highlighted on the hippocampal dysfunction and its correlation with an early degeneration of dopaminergic neurons in the VTA. In this issue, De Marco and Venneri test the hypothesis that the volume of the VTA nucleus in humans might be associated with cognitive features of AD.
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http://dx.doi.org/10.3233/JAD-180094DOI Listing
August 2019