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Background: Mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) diagnosis is based on cerebrospinal fluid (CSF) or neuroimaging biomarkers. Currently, non-invasive and inexpensive blood-based biomarkers are being investigated, such as neuronal-derived plasma exosomes (NPEs). Neuroinflammation and early vascular changes have been described in AD pathogenesis and can be traced in plasma and NPEs. However, they have not been studied in early onset MCI (EOMCI). Objective: To describe the rationale, design, and baseline characteristics of the participants from the BIOFACE cohort, a two-year observational study on EOMCI conducted at Fundació ACE. The study goal is to characterize the different phenotypes from a clinical, neuropsychological, and biomarker point of view and to investigate the CSF and plasma proteomics as well as the role of NPEs as early biomarkers of AD. Methods: Participants underwent extended neurological and neuropsychological batteries, multimodal biomarkers including brain MRI, blood, saliva, CSF, anthropometric, and neuro-ophthalmological examinations. Results: Ninety-seven patients with EOMCI were recruited. 59.8%were women. Mean age at symptom onset was 57 years; mean MMSE was 28. First degree and presenile family history of dementia was present in 60.8%and 15.5%, respectively. Depressive and anxiety disorders along with vascular risk factors were the most frequent comorbidities. 29%of participants were APOE ɛ4 carriers, and 67%showed a CSF normal ATN profile. Conclusion: BIOFACE is a two-year study of clinical, cognition, and biomarkers that will shed light on the physiopathology and the potential utility of plasma and NPEs as non-invasive early diagnostic and prognostic biomarkers in people younger than 65 years.

Summary Introduction Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the novel coronavirus disease (COVID-19) pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years. Aim To analyze the impact of the COVID-19 pandemic on the mental health of HPs. Method We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020. Results Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: (i) COVID-19 exposure; (ii) epidemiological issues; (iii) material resources; (iv) human resources; and (v) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs’ distress. Conclusion A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.

BACKGROUND: Fundacio ACE is a non-profit organization providing care based on a holistic model to persons with cognitive disorders and their families for 25 years in Barcelona, Spain. Delivering care to this vulnerable population amidst the COVID-19 pandemic has represented a major challenge to our institution. OBJECTIVE: To share our experience in adapting our model of care to the new situation to ensure continuity of care. METHODS: We detail the sequence of events and the actions taken within Fundacio ACE to swiftly adapt our face-to-face model of care to one based on telemedicine consultations. We characterize individuals under follow-up by the Memory Unit from 2017 to 2019 and compare the number of weekly visits in 2020 performed before and after the lockdown was imposed. RESULTS: The total number of individuals being actively followed by Fundacio ACE Memory Unit grew from 6,928 in 2017 to 8,147 in 2019. Among those newly diagnosed in 2019, most patients had mild cognitive impairment or mild dementia (42% and 25%, respectively). Weekly visits dropped by 60% following the suspension of face-to-face activity. However, by April 24 we were able to perform 78% of the visits we averaged in the weeks before confinement began. DISCUSSION: We have shown that Fundacio ACE model of care has been able to successfully adapt to a health and social critical situation as COVID-19 pandemic. Overall, we were able to guarantee the continuity of care while preserving the safety of patients, families, and professionals. We also seized the opportunity to improve our model of care.

Background: Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer's disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive decline (SCD) has been proposed as a risk factor for progression to AD. There is little data about retinal changes in preclinical AD and their correlation with amyloid-β (Aβ) uptake. Aims: We investigated the association of retinal thickness quantified by OCT with Aβ accumulation and conversion to mild cognitive impairment (MCI) over 24 months in individuals with SCD. Methods: One hundred twenty-nine individuals with SCD enrolled in Fundació ACE Healthy Brain Initiative underwent comprehensive neuropsychological testing, OCT scan of the retina and florbetaben (FBB) positron emission tomography (PET) at baseline (v0) and after 24 months (v2). We assessed the association of sixteen retinal thickness measurements at baseline with FBB-PET status (+/-) and global standardize uptake value ratio (SUVR) as a continuous measure at v0 and v2 and their predictive value on clinical status change (conversion to mild cognitive impairment (MCI)) at v2. Results: Mean age of the sample was 64.72 ± 7.27 years; 62.8% were females. Fifteen participants were classified as FBB-PET+ at baseline and 22 at v2. Every 1 μm of increased thickness in the inner nasal macular region conferred 8% and 6% higher probability of presenting a FBB-PET+ status at v0 (OR = 1.08, 95% CI = 1.02-1.14, p = 0.007) and v2 (OR = 1.06, 95% CI = 1.02-1.11, p = 0.004), respectively. Inner nasal macular thickness also positively correlated with global SUVR (at v0: β = 0.23, p = 0.004; at v2: β = 0.26, p = 0.001). No retinal measurements were associated to conversion to MCI over 24 months. Conclusions: Subtle retinal thickness changes in the macular region are already present in SCD and correlate with Aβ uptake. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 796706, and the Instituto de Salud Carlos III (ISCIII) grant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National R+D+I Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa") awarded to M.M. Funds were also obtained from donations from “La nit de l’Alzheimer”, a charity dinner initiative that takes place yearly as part of the “Festival Castell de Peralada” (2016-2018). The neuro-ophthalmology exam devices were acquired with a grant EFSD/Lilly Mental Health and Diabetes 2013 Programme of the European Foundation for the Study of Diabetes (EFSD) awarded to the project “Retinal neurodegeneration in type 2 diabetes as biomarker of Alzheimer’s disease” under the leadership of C.H. Funds from Fundació ACE Institut Català de Neurociències Aplicades, Grifols, Life Molecular Imaging, Araclon Biotech, Alkahest, Laboratorio de análisis Echevarne and IrsiCaixa are supporting the FACEHBI study. These sponsors were not involved in the study design, data collection, analysis or interpretation. The sponsors have reviewed the manuscript and have given their approval.

Introduction: Addictions among physicians are a matter of public health interest because of their negative impact on the physician’s well-being and the potential risk of malpractice. Physicians’ Health Programmes (PHP) have been developed in several countries to address this issue. Although they share some similarities, they differ in organisational and clinical aspects. Objective: This study aimed to describe the clinical outcomes of the Integral Treatment Programme for Addicted Physicians of The Galatea Care Programme for Sick Physicians (PAIMM). Methods: A prospective naturalistic longitudinal study was conducted using data from electronic medical records of 126 physicians registered at the Barcelona Medical Association-Council and admitted to the PAIMM between 2008 and 2016. All patients received addiction treatment supervised by a specialised team with individual visits (psychiatrist and psychologist), had regular and random drug screening, attended a 3-step intervention with 2 intensive initial phases and 2–5 year weekly group psychotherapy, and were monitored when they returned to practice. Results: All admitted physicians completed the intensive intervention, and 87.3% were subsequently monitored. The mean treatment length was 48 months. Overall, 72.2% of sick physicians remained abstinent at last contact. Good adherence to follow-up psychotherapy groups predicted both lower risk of lapse during the treatment process and higher rates of abstinence at follow-up. Conclusions: Initial intensive treatment, long-term follow-up and drug screening, group therapy attendance, and a case management approach are common factors that may explain the positive clinical outcomes for physicians with addictions in treatment at PHPs, regardless of the country.

ObjectivesLittle is known about resident physicians being treated at physician health programmes around the world despite the fact that it is a highly demanding training period. This study aims to describe the profiles of resident physicians accessing a specialised mental health service in Spain over a 20-year period and to compare them to consultant-grade physicians.DesignRetrospective observational study.SettingMedical records of the Galatea Care Programme for Sick Physicians.Participants1846 physicians registered at the Barcelona Medical Council-Association and admitted to the programme from January 1998 to December 2018.Primary and secondary outcome measuresNumber of admissions, sociodemographic and clinical variables, including medical specialty, main diagnosis and need of hospitalisation.ResultsResidents accounted for 18.1% (n=335) of the sample and admissions increased over the years. Most residents (n=311; 94.5%) and consultant-grade physicians (n=1391; 92.8%) were self-referred. The most common specialty among residents was family medicine (n=107; 31.9%), followed by internal medicine (n=18; 5.4%), paediatrics (n=14; 4.2%), psychiatry (n=13; 3.9%) and anaesthesiology (n=13; 3.9%). Residents, regardless of year of training, mainly asked for help because of adjustment (n=131; 39.1%), affective (n=77; 23%), anxiety disorders (n=40; 18.8%) and addictions (n=19; 5.7%). There were no significant differences between groups in the main diagnosis and in the variables related to need of hospitalisation. The percentage of residents accessing the programme was higher than in the reference population registered at the Barcelona Medical Council-Association (18.1% vs 7.6%; z=7.2, pConclusionsResidents are more likely than consultant-grade physicians to seek help when suffering from mental disorders. Local primary prevention actions since the beginning of their training period and having access to a well-known highly reliable programme may partly explain these findings.

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER) Altres ajuts: Generalitat de Catalunya. Programa CERCA Altres ajuts: Instituto de Salud Carlos III (CIBERSAM i CIBERNED) Altres ajuts: Fundació "La Caixa" Altres ajuts: Grífols SA (GR@ACE project) Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alzheimer's disease (AD) and other dementia types in patients diagnosed with Mild Cognitive Impairment (MCI). Our aim was to determine profiles based on the prominent NPS in MCI patients and to explore the predictive value of these profiles on conversion to specific types of dementia. A total of 2137 MCI patients monitored in a memory clinic were included in the study. Four NPS profiles emerged (classes), which were defined by preeminent symptoms: Irritability, Apathy, Anxiety/Depression and Asymptomatic. Irritability and Apathy were predictors of conversion to dementia (HR = 1.43 and 1.56, respectively). Anxiety/depression class showed no risk effect of conversion when compared to Asymptomatic class. Irritability class appeared as the most discriminant neuropsychiatric condition to identify non-AD converters (i.e., frontotemporal dementia, vascular dementia, Parkinson's disease and dementia with Lewy Bodies). The findings revealed that consistent subgroups of MCI patients could be identified among comorbid basal NPS. The preeminent NPS showed to behave differentially on conversion to dementia, beyond AD. Therefore, NPS should be used as early diagnosis facilitators, and should also guide clinicians to detect patients with different illness trajectories in the progression of MCI.

To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3-2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.

To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3–2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.

Background Family physicians (FPs) are said to be suffering from high rates of mental distress. Physicians’ health programmes (PHPs) have been developed in several countries to provide specialized care for those suffering from mental disorders. Objective To describe the profile of FPs admitted to the Integral Care Programme for Sick Physicians (PAIMM) compared to other physicians and the evolution of their referrals during a 20-year period. Methods We conducted a retrospective observational study of 1702 medical records of physicians registered at the Medical Council–Association of Barcelona and admitted to the PAIMM from 1998 to 2017. FPs represented 20% (n = 283) of all consultant-grade physicians (n = 1413). Results FPs’ admissions have increased over the years, mainly in the last decade. FPs were younger than other specialists (odds ratio [OR]: 0.97; 95% confidence interval [CI]: 0.96–0.99) and more likely to be women (OR: 1.42; 95% CI: 1.06–1.89). All PAIMM physicians had a high prevalence of both adjustment and affective disorders and the prevalence of addictions has decreased in the last decade. Conclusions The increase in FPs accessing PHPs in recent years is notable; however, the reasons behind this trend require deeper analysis at the personal, professional and institutional levels.

Little is known about the suicidal behaviour of health professionals admitted to specialised programmes. This study aims to describe the factors associated with high risk of suicide (HRS) of physicians and nurses in treatment at the Galatea Care Programme. We conducted a retrospective naturalistic study with data from 1,214 electronic medical records of physicians and nurses working in Catalonia and in treatment at the Galatea Clinic during 2017 and 2018. HRS was registered in the medical record according to the screening criteria of the Catalonia Risk Suicide Code; 62.4% (n = 757) were physicians and 37.6% (n = 457) were nurses. HRS was identified in 5% physicians and 5.2% nurses. Patients who were in a relationship or were not on a sick leave were less likely to have HRS, whereas those with affective disorders were more likely to have HRS compared with those with anxiety disorders or substance use disorders. Patients with HRS were more likely to have concurrent mental disorders. Specialised treatment programmes for health professionals should regularly screen for suicide risk, especially amongst those having affective disorders, comorbid mental disorders or when their working and interpersonal life areas are impaired.

Background Computerized neuropsychological tests for early detection of Alzheimer’s disease (AD) have attracted increasing interest. Memory for faces and proper names is a complex task because its association is arbitrary. It implicates associative occipito-temporal cerebral regions, which are disrupted in AD. The short form of the Face-Name Associative Memory Exam (FNAME-12), developed to detect preclinical and prodromal AD, asks individuals to learn the names and occupations associated with 12 faces. The current work advances this field by using voice recognition and touchscreen response format. The purpose of this study is to create the first self-administered episodic memory test, FACEmemory®, by adapting the FNAME-12 for tablet use with voice recognition, touchscreen answers, and automatic scoring. The test was minimally supervised by a psychologist to avoid technological problems during execution and scored manually to assess the reliability of the automatic scoring. The aims of the present study were (1) to determine whether FACEmemory® is a sensitive tool for the detection of cognitive impairment, (2) to examine whether performances on FACEmemory® are correlated with those on the S-FNAME (paper-and-pencil version with 16 images), and (3) to determine whether performances on FACEmemory® are related to AD biomarkers in the cerebrospinal fluid (CSF) (Aβ42, p-tau, and Aβ42/p-tau ratio). Methods FACEmemory® was completed by 154 cognitively healthy (CH) individuals and 122 subjects with mild cognitive impairment, of whom 61 were non-amnestic (naMCI) and 61 amnestic (aMCI). A subsample of 65 individuals completed the S-FNAME, and 65 subjects received lumbar punctures. Results Performance on FACEmemory® was progressively worse from CH to the naMCI and aMCI groups. A cutoff of 31.5 in total FACEmemory® obtained 80.5% and 80.3% sensitivity and specificity values, respectively, for discriminating between CH and aMCI. Automatically corrected FACEmemory® scores were highly correlated with the manually corrected ones. FACEmemory® scores and AD CSF biomarker levels were significantly correlated as well, mainly in the aMCI group. Conclusions FACEmemory® may be a promising memory prescreening tool for detecting subtle memory deficits related to AD. Our findings suggest FACEmemory® performance provides a useful gradation of impairment from normal aging to aMCI, and it is related to CSF AD biomarkers.

To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (Aβ) deposition and regional volumetric reduction in areas of interest for Alzheimer’s disease (AD). 195 individuals with SCD from the FACEHBI study were assessed with a neuropsychological battery that included the following nine executive function tests: Trail Making Test A and B (TMTA, TMTB), the Rule Shift Cards subtest of BADS, the Automatic Inhibition subtest of the Syndrom Kurz Test (AI-SKT), Digit Span Backwards and Similarities from WAIS-III, and the letter, semantic, and verb fluency tests. All subjects underwent an 18F-Florbetaben positron emission tomography (FBB-PET) scan to measure global standard uptake value ratio (SUVR), and a magnetic resonance imaging (MRI). A multiple regression analysis, adjusted for age, was carried out to explore the association between global SUVR and performance on executive tests. Then, on those tests significantly associated with amyloid burden, a voxel-based morphometry (VBM) analysis was carried out to explore their correlates with grey matter volume. Multiple regression analysis revealed a statistically significant association between Aβ deposition and performance on one of the executive tests (the AI-SKT). Moreover, VBM analysis showed worse AI-SKT scores were related to lower volume in bilateral hippocampus and left inferior frontal regions. In conclusion, in SCD individuals, worse automatic inhibition ability has been found related to higher cerebral Aβ deposition and lower volume in the hippocampus and frontal regions. Thus, our results may contribute to the early detection of AD in individuals with SCD.

The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer’s Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer’s disease’s (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 µm, MCI group: 98,54 ± 14,43 µm and AD group: 96,61 ± 15,27 µm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119), nasal (p = 0,151), superior (p = 0,435) or inferior (p = 0,825) quadrants between AD, MCI and control groups. These results do not support the usefulness of peripapillary RNFL analysis as a marker of cognitive impairment or in discriminating between cognitive groups. The analysis of other OCT measurements in other retinal areas and layers as biomarkers for AD should be tested further.

Abstract. The study examines the relationship between a categorical and a dimensional personality assessment instrument in patients with Chronic Fatigue Syndrome (CFS). A total of 162 CFS patients were included in the study (91.4% women; mean age 47.5 years). All subjects completed the Spanish versions of the Personality Diagnostic Questionnaire-4+ (PDQ-4+) and the Temperament and Character Inventory-Revised (TCI-R). Results: 78 (48.1%) of the patients presented a Personality Disorder (PD), the most frequent being Cluster C, specifically Obsessive-compulsive disorder, followed by Avoidant disorder. PDs showed a specific pattern of correlation with temperament scales. All PD clusters correlated positively with Harm Avoidance and Self-Transcendence, and negatively with Reward Dependence, Self-Directedness, and Cooperativeness. In a logistic regression analysis, Self-Directedness and Cooperativeness predicted PD presence. The findings are consistent with previous studies in non-CFS samples and suggest that the combination of the Temperament and Character dimensions (low Self-Directedness and Cooperativeness and high Harm Avoidance and Self-Transcendence) correlates with PD severity, and that Self-Directedness and Cooperativeness are associated with PD presence in CFS patients. The integration of these two perspectives expands the current comprehension of personality pathology in CFS patients.

BACKGROUNDDisentangling the genetic constellation underlying Alzheimer’s disease (AD) is important. Doing so allows us to identify biological pathways underlying AD, point towards novel drug targets and use the variants for individualised risk predictions in disease modifying or prevention trials. In the present work we report on the largest genome-wide association study (GWAS) for AD risk to date and show the combined utility of proven AD loci for precision medicine using polygenic risk scores (PRS).METHODSThree sets of summary statistics were included in our meta-GWAS of AD: an Spanish case-control study (GR@ACE/DEGESCO study, n = 12,386), the case-control study of International Genomics of Alzheimer project (IGAP, n = 82,771) and the UK Biobank (UKB) AD-by-proxy case-control study (n=314,278). Using these resources, we performed a fixed-effects inverse-variance-weighted meta-analysis. Detected loci were confirmed in a replication study of 19,089 AD cases and 39,101 controls from 16 European-ancestry cohorts not previously used. We constructed a weighted PRS based on the 39 AD variants. PRS were generated by multiplying the genotype dosage of each risk allele for each variant by its respective weight, and then summing across all variants. We first validated it for AD in independent data (assessing effects of sub-threshold signal, diagnostic certainty, age at onset and sex) and tested its effect on risk (odds for disease) and age at onset in the GR@ACE/DEGESCO study.FINDINGSUsing our meta-GWAS approach and follow-up analysis, we identified novel genome-wide significant associations of six genetic variants with AD risk (rs72835061-CHRNE, rs2154481-APP, rs876461-PRKD3/NDUFAF7, rs3935877-PLCG2 and two missense variants: rs34173062/rs34674752 in SHARPIN gene) and confirmed a stop codon mutation in the IL34 gene increasing the risk of AD (IL34-Tyr213Ter), and two other variants in PLCG2 and HS3ST1 regions. This brings the total number of genetic variants associated with AD to 39 (excluding APOE). The PRS based on these variants was associated with AD in an independent clinical AD-case control dataset (OR=1.30, per 1-SD increase in the PRS, 95%CI 1.18-1.44, p = 1.1×10−7), a similar effect to that in the GR@ACE/DEGESCO (OR=1.27, 95%CI 1.23-1.32, p = 7.4×10−39). We then explored the combined effects of these 39 variants in a PRS for AD risk and age-at-onset stratification in GR@ACE/DEGESCO. Excluding APOE, we observed a gradual risk increase over the 2% tiles; when comparing the extremes, those with the 2% highest risk had a 2.98-fold (95% CI 2.12–4.18, p = 3.2×10−10) increased risk compared to those with the 2% lowest risk (p = 5.9×10−10). Using the PRS we identified APOE ε33 carriers with a similar risk as APOE ε4 heterozygotes carriers, as well as APOE ε4 heterozygote carriers with a similar risk as APOE ε4 homozygote. Considering age at onset; there was a 9-year difference between median onset of AD the lowest risk group and the highest risk group (82 vs 73 years; p = 1.6×10−6); a 4-year median onset difference (81 vs 77 years; p = 6.9×10−5) within APOE ε4 heterozygotes and a 5.5-year median onset difference (78.5 vs 73 years; p = 4.6×10−5) within APOE ε4 carriers.INTERPRETATIONWe identified six novel genetic variants associated with AD-risk, among which one common APP variant. A PRS of all genetic loci reported to date could be a robust tool to predict the risk and age at onset of AD, beyond APOE alone. These properties make PRS instrumental in selecting individuals at risk in order to apply preventative strategies and might have potential use in diagnostic work-up.

Building on previous studies that report thinning of the macula in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients, the use of optical coherence tomography (OCT) has been proposed as a potential biomarker for AD. However, other studies contradict these results. A total of 930 participants (414 cognitively healthy people, 192 with probable amnestic MCI, and 324 probable AD patients) from a memory clinic were consecutively included in this study and underwent a spectral domain OCT scan (Maestro, Topcon) to assess total macular volume and thickness. Macular width measurements were also taken in several subregions (central, inner, and outer rings) and in layers such as the retinal nerve fiber (RNFL) and ganglion cell (CGL). The study employed a design of high ecological validity, with adjustment by age, education, sex, and OCT image quality. AD, MCI, and control groups did not significantly vary with regard to volume and retinal thickness in different layers. When these groups were compared, multivariate-adjusted analysis disclosed no significant differences in total (p = 0.564), CGL (p = 0.267), RNFL (p = 0.574), and macular thickness and volume (p = 0.380). The only macular regions showing significant differences were the superior (p = 0.040) and nasal (p = 0.040) sectors of the inner macular ring. However, adjustment for multiple comparisons nullified this significance. These results are not supporting existing claims for the usefulness of macular thickness as a biomarker of cognitive impairment in a memory unit. OCT biomarkers for AD should be subject to further longitudinal testing. The authors thank the study participants and their families for their collaboration, and Topcon for its reliability as technological partnership. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 796706 awarded to MM; from Fundació ACE Institut Català de Neurociències Aplicades in Barcelona, Spain and from a donation of “La nit de l’Alzheimer”, a charity dinner initiative that took place on August 8th 2016 as part of the “Festival Castell de Peralada”. The neuro-ophthalmology exam devices were acquired with a grant EFSD/Lilly Mental Health and Diabetes 2013 Programme of the European Foundation for the Study of Diabetes (EFSD) awarded to the project “Retinal neurodegeneration in type 2 diabetes as biomarker of Alzheimer’s disease” under the leadership of CH. The present work was performed as part of Domingo Sánchez Ruiz’ doctoral program with title “Clinical Utility of OCT in diagnosing and monitoring of cognitive impairment” in the Department of Surgery and Morphological Sciences at Universitat Autonoma Barcelona (Barcelona, Spain).

The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer's Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer's disease's (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 µm, MCI group: 98,54 ± 14,43 µm and AD group: 96,61 ± 15,27 µm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119), nasal (p = 0,151), superior (p = 0,435) or inferior (p = 0,825) quadrants between AD, MCI and control groups. These results do not support the usefulness of peripapillary RNFL analysis as a marker of cognitive impairment or in discriminating between cognitive groups. The analysis of other OCT measurements in other retinal areas and layers as biomarkers for AD should be tested further.

The Zuckerman-Kuhlman Personality Questionnaire (ZKPQ; Zuckerman, Kuhlman, Joireman, Teta,Kraft, 1993 ) was designed for the assessment of personality. The goal of this work was to determine the psychometric properties of the ZKPQ, as well as to establish normative data by gender and age in an outpatient sample attending primary mental health care services. We administered the questionnaire to 314 participants (34.7% males) 18 to 81 years old. The most prevalent primary diagnoses were mood (37.9%) and adjustment disorders (35.0%). Concerning the psychometric properties of the ZKPQ, the pattern of internal consistencies was similar to that previously found among general population, student, or clinical samples. Regarding gender differences, a general pattern was found, with women scoring higher on neuroticism and sociability, and lower on aggression-hostility. As for age, in general, scores declined with age. Norm-based decision making has the potential for significant and long-lasting consequences, and the quality of decisions based on score comparisons can be improved when scores are compared to norms fitted to the group of reference. The availability of the ZKPQ norms by gender and age in mental health care will benefit the accuracy of assessment and therapeutic decision making, providing more effective treatment planning overall.

Cortisol awakening response (CAR) has been studied in children with ADHD, and some authors have reported morning cortisol differences among ADHD subtypes. Despite, only half of the children with ADHD continue to exhibit the disorder into adulthood, CAR has not been studied in adults so far. One hundred and nine adults with ADHD according to the DSM-IV criteria (46 inattentive and 63 combined) ranging in age from 18 to 55 years, and 27 healthy controls were included. Psychiatric and organic comorbidities were excluded. Salivary cortisol samples were obtained at 0, 30, 45 and 60 minutes after awakening. CAR was present in 84% of the healthy controls but in only 64% of the adults with ADHD (68% of the inattentive and 61% of the combined were CAR-positive). There were no significant differences in any of the morning cortisol measures between patients and controls or between the combined and inattentive subtypes of ADHD. Among the inattentive subtype but not in the combined patients, significant positive correlations were observed between the CAR and emotional lability (p=0.05), or self-concept (p=0.014) CAARS subscales, as well as with the cognitive impulsivity subscale of the Barratt impulsiveness scale (p=0.028). These results suggest that adults with ADHD exhibit normal cortisol responses upon awakening and thus cannot be defined in terms of hypo-arousal. Neurobiological differences between the combined and inattentive subtypes involving cortisol, are discussed.

Background: The existing pharmacological treatments for Alzheimer’s disease (AD) can only slow the progression of symptoms or delay admission to long-term care facilities. The beneficial effects of non-drug treatments are poorly studied. Objective: To describe the effects of an Integrated Psychostimulation Program (IPP) in patients with mild-moderate AD treated with acetylcholinesterase inhibitors; and to identify factors related to greater benefit of the IPP. Methods: 206 patients (mean age = 75.9 years; MMSE = 19.6) were evaluated before starting the IPP and 3, 6, 9, and 12 months later. Measures included: Mini-Mental State Examination (MMSE), Cognitive Subscale of Alzheimer’s Disease Assessment Scale (ADAS-Cog), Rapid Disability Rating Scale (RDRS-2), and Neuropsychiatric Inventory Questionnaire (NPI-Q). Results: Patients remained cognitively stable (MMSE/ADAS-Cog) for more than 6 months and significantly worsened at 9-month and 12-month follow-ups, without clinically significant functional changes (RDRS-2) or psychiatric symptoms(NPI-Q). The mean annual change on MMSE and ADAS-Cog were 2.06 and 3.56 points, respectively, lower than the annual decline demonstrated previously in similar patients (2.4 and 4.5, respectively). 42.7% of patients maintained or improved global cognitive scores between baseline and 12-month follow-up. The patients who maintained cognitive functions were older than those who did not (77.5 versus 74.7 years). Conclusions: The IPP may be an effective treatment to maintain cognition, functionality, and psychiatric symptoms in AD patients pharmacologically treated, and older age seems to increase beneficial effects of IPP.

Recent data regarding the persistence or remittance of attention deficit-hyperactivity disorder (ADHD) diagnosis into adulthood raise the question of its possible role in crucial public health issues, including road safety, especially when neurocognitive capacities are challenged.The study included 611 participants with serious traffic violations. The Spanish version of the Mini International Neuropsychiatric Interview (M.I.N.I.) was used to assess psychopathology. They were grouped into 3 diagnostic conditions: non-ADHD, persistent ADHD (ADHD-P), and remittent ADHD (ADHD-R). Several risky driving behaviors were analyzed.Although participants with ADHD have more driving violations relative to non-ADHD, ADHD-R, and ADHD-P drivers have similar profiles. ADHD-R and ADHD-P drivers are more prone to perform risky and recidivistic behaviors relative to non-ADHD counterparts (P = .044 and P = .047, respectively); ADHD-R and ADHD-P participants are statistically comparable in this proneness (P = .772).These results suggest that the underlying core deficits of ADHD-attention and other executive disabilities-persist despite the fact that some people no longer reach the threshold for clinical diagnosis.

The role of genetic risk markers for Alzheimer's disease (AD) in mediating the neurocognitive endophenotypes (NEs) of subjects with mild cognitive impairment (MCI) has rarely been studied. The aim of the present study was to investigate the relationship between well-known AD-associated single-nucleotide polymorphisms (SNPs) and individual NEs routinely evaluated during diagnosis of MCI, AD, and other dementias. The Fundació ACE (ACE) dataset, comprising information from 1245 patients with MCI, was analyzed, including the total sample, amnestic MCI (aMCI) (n = 811), and non-amnestic MCI (naMCI) (n = 434). As probable-MCI (Pr-MCI) patients with memory impairment have a higher risk of AD, which could influence the statistical power to detect genetic associations, the MCI phenotype was also stratified into four related conditions: Pr-aMCI (n = 262), Pr-naMCI (n = 76), possible (Pss)-aMCI (n = 549), and Pss-naMCI (n = 358). Validation analyses were performed using data from the German study on Aging, Cognition, and Dementia in primary care patients (AgeCoDe), and the German Dementia Competence Network (DCN). SNP associations with NEs were calculated in PLINK using multivariate linear regression analysis adjusted for age, gender, and education. In the total MCI sample, APOE-ε4 was significantly associated with the memory function NEs 'delayed recall (DR)' (β = -0.76, p = 4.1 × 10-10), 'learning' (β = -1.35, p = 2.91 × 10-6), and 'recognition memory' (β = -0.58, p = 9.67 × 10-5); and with 'DR' in the aMCI group (β = -0.36, p = 2.96 × 10-5). These results were confirmed by validation in the AgeCoDe (n = 503) and DCN (n = 583) datasets. APOE-ε4 was also significantly associated with the NE 'learning' in individuals classified as having Pss-aMCI (β = -1.37, p = 5.82 × 10-5). Moreover, there was a near study-wide significant association between the HS3ST1 locus (rs6448799) and the 'backward digits' working memory NE (β = 0.52, p = 7.57 × 10-5) among individuals with Pr-aMCI, while the AP2A2 locus (rs10751667) was significantly associated with the language NE 'repetition' (β = -0.19, p = 5.34 × 10-6). Overall, our findings support specific associations of established AD-associated SNPs with MCI NEs.

Background: A rare coding variant (rs72824905, p.P522R) conferring protection against the susceptibility to Alzheimer's disease (AD) was recently identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2). Here, we explore the protective nature of this variant with regard to AD pathology indicated by biomarkers, cognitive decline, and potential underlying biological mechanisms. Methods: Association of p.P522R with CSF levels of pTau181, total Tau and Aβ1-42 was assessed in 1,282 patients with mild cognitive impairment (MCI) or AD-dementia syndrome. In addition, the association with longitudinal cognitive decline was tested in 3,010 MCI patients from memory clinic cohorts and 10,100 individuals from population-based studies using latent process linear mixed models. Finally, unsupervised co-trans-regulatory network analysis and biological experiments were conducted. Findings: Carriers of the p.P522R variant showed lower pTau181 levels in CSF compared to non-carriers, specifically in the presence of amyloid pathology. In MCI patients but not in population-based cohorts, the p.P522R variant was associated with slower cognitive decline with an effect size similar to that of APOE-e4. We identified a network of coregulated proteins linking PLCG2 to APOE and TREM2. Finally, in vitro experiments confirmed that inflammasome activation upon phospholipase C stimulation might act downstream of PLCG2. Implication: Our data link the protective effect of p.P522R in PLCG2 to reduced Tau pathology, to a slower cognitive decline in MCI patients and to underlying inflammatory processes. Therapies targeting the enzyme PLCG2 might provide a therapeutic approach for AD. Funding Statement: EU Joint Programme Neurodegenerative Disease Research, Innovative Medicines Initiative 2, Instituto de Salud Carlos III, La Caixa, Grifols SA, German Federal Ministry of Research and Education, Sanofi Laboratories, Fondation pour la Recherche Medicale, Fondation Plan Alzheimer, Stichting Alzheimer Nederland, Stichting VUmc fonds, Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care, Netherlands Organization for Scientific Research (NWO), EMGO+ Research Institute. Declaration of Interests: All authors report no conflict of interest. PL received consultation and/or lecture honoraria from IBL International, Fujirebio Europe, AJ Roboscreen, and Roche. JW received honoraria for consulting activities, lectures or advisory board participation from Pfizer, Eli Lilly, Hoffmann-La-Roche, MSD Sharp + Dome, Janssen-Cilag GmbH, Immungenetics AG, Boehringer Ingelheim. LF received honoraria for consulting activities, lectures or advisory board participation from Allergan, Eli Lilly, Avraham Pharmaceuticals, Axon Neuroscience, Axovant, Biogen, Boehringer Ingelheim, Eisai, Functional Neuromodulation, Lundbeck, MerckSharpe & Dohme, Novartis, Pfizer, Pharnext, Roche, Schwabe Pharma; he served on Data and Safety Monitoring boards or endpoint committees with Avraham Pharmaceuticals, Axon Neuroscience, Forschungszentrum Julich, Novartis, Pharmatropix. JP received honoraria for consulting activities, lectures or advisory board participation from Fujirebio Europe, Ono Pharma, Eli Lilly, and Nestle Institute of Health Sciences. ARu reports consulting Fees: Landsteiner Genmed, Grifols, Araclon biotech. And Lecture Fees: Araclon Biotech.PA reports personal fees from Servier, Total, Genoscreen, Takeda, Foundation Alzheimer. OP received research funding, consultancy fees or speech honoraria from Axovant, Biogen, Genentech, Lilly, Lundbeck, Novartis, Pharmatrophix, Piramal, Probiodrug, Roche, Takeda and TauRx Pharmaceuticals. MB receives fees or has received for consulting from Lab. Servier, Roche, Lilly, Avid, Bayer, Elan, Janssen, Neuroptix, Sanofi. She receives or has received fees for lectures from Lilly, Nutricia, Roche, Schwabe, Araclon, Esteve, Grifols, Janssen, Novartis, Piramal, Pfizer-Wyett, Servier. She receives fees for being part of the Advisory Board of Lilly and Schwabe. She reports grants/research funding from Abbvie, Araclon, Biogen Research Limited, Bioiberica, Grifols, Lilly, S.A, Merck Sharp & Dohme, Kyowa Hakko Kirin, Laboratorios Servier, Nutricia SRL, Oryzon Genomics, Piramal Imaging Limited, Roche Pharma SA, and Schwabe Farma iberica SLU, all outside the submitted work. She has not received personal compensations from these organizations Ethics Approval Statement: The individual studies were approved by the respective ethics committees.

Background and objectivesBorderline Personality Disorder (BPD) is one of the most complex personality disorders (PD). The Borderline Personality Disorder Checklist (BPD Checklist) is an instrument specifically designed to assess the burden of BPD symptoms according to DSM-IV/5 criteria in the past month.MethodsOur goal was to adapt and validate the BPD Checklist in Spanish and to study its psychometric properties, i.e. reliability and validity. We administered it in a sample of BPD patients (n = 342) and in a sample of patients with other PD diagnoses (n = 190).ResultsThe results obtained indicated that the psychometric properties of the Spanish version of the BPD Checklist are similar to those of the original version of the instrument. The internal consistency indices were generally good to excellent. The total score and the subscales of the BPD Checklist discriminated between diagnostic samples. As expected, the subscales were associated with the scores on the SCID-II and self-rating measures.ConclusionsOur results are consistent with the original version of BPD Checklist. In general, it is an adequate instrument for clinical screening and to assess the subjective burden of BPD experienced by the patient in the past month.

BackgroundVerb fluency (VF) is the less commonly used fluency test, despite several studies suggesting its potential as a neuropsychological assessment tool. Objective: To investigate the presence of VF deficits in mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) dementia; to assess the usefulness of VF in the detection of cognitively healthy (CH) people who will convert to MCI, and from MCI to dementia; and to establish the VF cut-offs useful in the cognitive assessment of Spanish population.Methods568 CH, 885 MCI, and 367 mild AD dementia individuals were administered the VF test and a complete neuropsychological battery. Longitudinal analyses were performed in 231 CH and 667 MCI subjects to search for VF predictors of diagnosis conversion.ResultsA worsening on VF performance from CH, MCI to AD dementia groups was found. Lower performances on VF were significantly related to conversion from CH to MCI/MCI to dementia. When the effect of time to conversion was analyzed, a significant effect of VF was found on the faster conversion from CH to MCI, but not from MCI to dementia. Moreover, VF cut-off scores and sensitivity/specificity values were calculated for 6 conditions (3 age ranges by 2 educational levels). ConclusionThe VF test may be a useful tool for the differential diagnosis of cognitive failure in the elderly. Since VF deficits seem to take place in early stages of the disease, it is a suitable neuropsychological tool for the detection not only of CH people who will convert to MCI, but also from MCI to dementia.

The Face-Name Associative Memory Exam (FNAME) is a paired associative memory test created to detect memory deficits in individuals with preclinical Alzheimer’s disease (AD). Worse performance on FNAME in cognitively healthy individuals were found related to higher amyloid beta (Aβ) burden measured with Positron-Emission-Tomography using 11C-PiB (PiB-PET). We previously reported normative data of a Spanish version of FNAME (S-FNAME) in cognitively healthy Spanish-speaking subjects. The aim of the present study was to determine whether performance on S-FNAME was associated with Aβ burden in subjective cognitive decline (SCD) individuals. 200 SCD subjects received neurological and neuropsychological assessments, including the S-FNAME and the Word List task from the Wechsler-Memory-Scale-III (WMS-III). Moreover, they received an MRI and (18)F-Florbetaben Positron-Emission-Tomography (FBB-PET) to measure Aβ burden. Three cognitive factor composites were derived for the episodic memory measures (face-name [SFN-N], face-occupation [SFN-O] and WMS-III) to determine whether episodic memory performance was related to Aβ deposition. Higher global Aβ deposition was significantly related to worse performance on SFN-N but not with SFN-O or WMS-III Composite. Moreover, worse SFN-N performance was significantly related to higher Aβ deposition in bilateral Posterior Cingulate Cortex. The S-FNAME may be a promising neuropsychological tool for detecting SCD individuals with preclinical AD.

Background: Different interpretations of cognitive impairment and dementia due to differences in health structures, such as cultural differences could affect the diagnosis and treatment of the condition. it is reasonable to expect that the social and family impact of the disease and coping strategies will differ among societies. Objective: The general aim of this study is to understand the social representations of dementia, its associated practices, and the effects they imply. Methods: People diagnosed with clinical dementia and their families were assessed from 2005 to 2015 in the memory clinic of the Fundacio ́ ACE, Institut Catala` de Neurocie`ncies Aplicades in Barcelona, Spain. Results: 9,898 people were examined and 5,792 were diagnosed with dementia. For those with a caregiver (71%), the decision-making fell on the person with dementia in 16.2% of the cases; and for those without a caregiver, in 26.4% of the cases the family did not perceive the deficits as a disease, which led to multiple risk situations (74.6%). Conclusions: The recognition of dementia as part of aging is common among families. Consequently, risk situations may arise and diagnosis and access to treatment may be delayed. The incorporation of a social appraisal to the diagnostic process is a necessity to evaluate these situations.

Introduction Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. Methods We evaluated apolipoprotein E ( APOE ) e4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Results Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE e4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. Discussion The FACEHBI sample presents APOE e4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype.

Objective: The aim of this study is to assess the discriminative value of emotional lability (EL) in the diagnosis of adults with ADHD. Methods: A group of adults who met ADHD DSM-IV diagnostic criteria (n = 589), a clinical control group (n = 138) and a community control group (n = 98) were compared in EL scores. SCID-I, SCID-II and CAADID were used to select subjects. The specific subscale on EL of the Conners Adult ADHD Rating Scale (CAARS) was used to evaluate EL. Results: An analysis of the covariance was carried out in order to explore the association between EL, ADHD and comorbidity. The group factor (ADHD, clinical or community group) and the comorbidity factor (presence or absence of other psychiatric disorders different from ADHD) showed to be significant on EL intensity (group: F = 81.78 p = 0.000; comorbidity: F = 25.48 p = 0.000). However, no significant differences were found in the group × comorbidity interaction (F = 1.006, p = 0.366). EL showed a sensitivity of 87.1% and a specificity of 46.6% in discriminating between ADHD patients and subjects with other psychiatric disorders. Conclusion: EL is specifically related to ADHD and this association is not explained for the presence of other psychiatric disorders. The presence of comorbid disorders is only related to a major intensity of EL. © 2014 Elsevier Inc. All right reserved.

This study explored the clinical features of physicians and nurses with dual diagnosis. We conducted a retrospective review of 150 medical records of physicians (n = 120) and nurses (n = 30) admitted from February 2008 to February 2011 to the Barcelona Psychiatric Inpatient Unit for Health Professionals. Routine intake included the Spanish version of the Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) and a clinical interview. The mean age of participants was 48.59 (SD = 8.9) years and 57.3% were male. Patients experienced substance dependence with alcohol (n = 112, 74.7%), sedatives (n = 59, 39.3%), cocaine (n = 24, 16%), other stimulants (n = 15, 10%), and opiates other than heroin (n = 16, 10.7%). About 41% (n = 61) also met criteria for a mental health disorder, mainly major depressive disorder (n = 42, 28%), while 8% (n = 12) had attention deficit hyperactivity disorder. A high proportion of physicians (n = 95, 79.2%) and nurses (n = 25, 83.3%) had nicotine dependence. The most common comorbidity was alcohol dependence and major depressive disorder. No differences were found between groups in the prevalence of substance use disorders, mental health disorders, and dual diagnosis. Dual diagnosis is a common condition among inpatient physicians and nurses with substance use disorders and its clinical presentation may be similar in both groups.

Objective The main objective was to explore early-age conditions associated to Substance Use Disorders (SUD) in adults with Attention Deficit/Hyperactivity Disorder (ADHD); secondly, to determine which of those conditions are specific to ADHD subjects; and finally, to compare ADHD and non-ADHD subjects in terms of SUD lifetime prevalence and professional, social and personal adjustment. Method Comparison between ADHD adults with (n = 236) and without lifetime SUD (n = 309) regarding clinical characteristics of ADHD, externalization disorders, temperamental traits, environmental factors, academic history and family psychiatric history; secondly, ADHD subjects were compared to a non-ADHD group (n = 177) concerning those variables. Results The following variables were found to be positively associated to SUD in ADHD subjects: ADHD severity, CD and ODD comorbidities, temperamental characteristics (“fearful”, “accident prone” and “frequent temper tantrums”), “sexual abuse”, “be suspended from school”, family history of SUD and ADHD, and male gender; ADHD inattentive subtype and “fearful” were inversely associated to SUD. From those variables, “frequent temper tantrums” was also associated to SUD in non-ADHD subjects. ADHD subjects had higher prevalence of lifetime SUD and greater professional, social and personal impairment than non-ADHD subjects. Conclusion Findings suggest a significant association between ADHD, SUD and early-age conditions, such as CD and ODD comorbidity; other variables from childhood, namely, ADHD subtype, temper characteristics (“fearful”, “accident prone”), “sexual abuse”, “be suspended from school” and family history of ADHD are associated to SUD in ADHD subjects, but not in non-ADHD subjects. Moreover, this study confirms both the higher prevalence of lifetime SUD and greater professional, social and personal impairment in ADHD subjects than in non-ADHD subjects.

Acute spinal cord injury leaves patients severely impaired and generates high levels of psychological distress among them and their families, which can cause a less active role in rehabilitation, worse functional recovery, and less perceived satisfaction with the results. Additionally, rehabilitation professionals who deal with this psychological distress could ultimately experience higher stress and more risk of burnout. This article presents the study protocol of the ESPELMA project, aimed to train rehabilitation professionals in the clinical management of acute spinal cord injury–associated psychological distress, and to measure the impact of this training on the patients’ perceived satisfaction with treatment.

Objective Previous studies have reported consistent associations between Neuroticism, maladaptive perfectionism and depression with severity of fatigue in Chronic Fatigue Syndrome (CFS). Depression has been considered a mediator factor between maladaptive perfectionism and fatigue severity, but no studies have explored the role of neuroticism in a comparable theoretical framework. This study aims to examine for the first time, the role of neuroticism, maladaptive perfectionism and depression on the severity of CFS, analyzing several explanation models. Methods A sample of 229 CFS patients were studied comparing four structural equation models, testing the role of mediation effect of depression severity in the association of Neuroticism and/or Maladaptive perfectionism on fatigue severity. Results The model considering depression severity as mediator factor between Neuroticism and fatigue severity is the only one of the explored models where all the structural modeling indexes have fitted satisfactorily (Chi square = 27.01, p = 0.079; RMSE = 0.047, CFI = 0.994; SRMR = 0.033). Neuroticism is associated with CFS by the mediation effect of depression severity. This personality variable constitutes a more consistent factor than maladaptive perfectionism in the conceptualization of CFS severity.

Background and Objectives Attention deficit hyperactivity disorder (ADHD) is highly prevalent among drug abusers. We studied the psychiatric comorbidity and characteristics of cocaine use in relation to the presence of ADHD among patients with cocaine dependence. Methods A total of 200 cocaine-dependent patients attending an Outpatient Drug Clinic participated in the study. A systematic evaluation of ADHD (CAADID-II), the severity of addiction (EuropASI) and other axes I and II psychiatric disorders was made (SCID-I and SCID-II). A descriptive, bivariate, and multivariate analysis of the data was performed. Results In the multivariate analysis, the identified risk factors for the development of ADHD were a history of behavioral disorder in childhood (OR: 3.04), a lifetime history of cannabis dependence in the course of life (OR: 2.68), and age at the start of treatment (OR: 1.08). The bivariate analysis showed ADHD to be associated with other factors such as male gender, age at start of cocaine use and dependence, the amount of cocaine consumed weekly, increased occupational alteration, alcohol consumption, general psychological discomfort, depressive disorder, and antisocial personality disorder. Conclusions and Scientific Significance We conclude that ADHD is associated with increased psychiatric comorbidity and greater severity of addiction. (Am J Addict 2013;22:466–473)

Background The persistence of risky behaviors while driving and traffic accidents despite campaigns to increase awareness suggest that there may be underlying causes that maintain proneness to traffic violations. The aim of the current study was to assess: a) the prevalence of psychopathology in a sample of people who have lost their driving license due to former traffic violations and b) the discriminatory capacity of each psychopathological disorder to differentiate among people with high and low proneness to perform risky behaviors while driving. Methods 383 participants in a course to recover their driving license after its loss due to previous traffic violations were included. The International Neuropsychiatric Interview (M.I.N.I.) according to DSM-IV was used to assess psychopathology. Results Between 67% and 76.2% of the participants had been affected by a lifetime psychopathological disorder until the moment of assessment. The most prevalent diagnoses were substance abuse including alcohol (52.5–62.7%), ADHD (19.7–28.5%), depression (7.9–14.4%) and anxiety (3.6–12.4%). Substance abuse and ADHD also showed the strongest set of associations with specific risk behaviors, but ADHD emerged as the most discriminant disorder to distinguish between those people at high and low risk of while driving. Conclusions The results of the current study suggest that addressing psychopathology explicitly to prevent risky behaviors and recidivism while driving would provide benefits in this area.

Workplace smoking cessation interventions increase quit rates compared to no treatment or minimal interventions. However, most studies report data up to one year. This study aims to evaluate long-term effects of a worksite smoking cessation intervention based on cognitive behavioral cessation groups combined with first-line medications, and determine to what extent cigarette dependence (FTCD) and depressive symptoms may influence results at five-year follow-up. Participants were invited to answer a short survey five years after starting the program. A total of 90.4% (n=227) of those who had attended at least one treatment session and were alive, completed the survey. At the five-year follow-up, 29.5% participants reported continuous abstinence. Low scores in the FTCD and low depressive symptoms at baseline predicted continuous abstinence. Three out of four continuous abstainers at twelve months remained abstinent at the five-year follow-up. The study shows that workplace smoking cessation interventions have long-term effects and supports the traditional one-year follow-up period to assess smoking cessation.

Objective: To examine the demographic and clinical differences between men and women admitted to a Physicians’ Health Programme (PHP). Method: Retrospective chart-review of 778 medical records of physicians admitted to the Barcelona PHP from February 1st 1998 until December 31st 2015. Results: Women admitted to the Barcelona PHP were younger than men, were more likely to be self-referred and to be admitted forfor a non-addictive mental disorder. Prevalence of unipolar affective disorders (60.1% vs. 37.6%), adjustment disorders (62.4% vs. 37.6%) and obsessive-compulsive disorder (61.1% vs. 38.9%) was significantly higher among women while prevalence of alcohol use disorders was lower (32.7% vs. 67.3%). Nevertheless, both groups were similar with regards to medical specialty, working status, length of their first treatment episode, and presence of hospitalization during that episode. After multivariate analysis, age, type of referral and main diagnosis (addictive disorders vs. other mental disorders) discriminated the differences between groups. Conclusions: Women physicians seem to be more prone to voluntarily ask for help from PHPs and are more likely to suffer from mood and anxiety disorders compared to men. However, mental disorders’ severity may be similar in both groups. More studies are needed to clarify the gender factors related to this behavior.

The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual impairment from normal aging through Alzheimer's disease (AD) and correlates with temporo-parietal perfusion. The objectives of this study were to analyze progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and its correlates with cognition and single photon emission computerized tomography (SPECT), as well as to examine neuropsychological and SPECT differences between the MCI patients who developed AD and those who did not. From the initial 126 participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two years. The progression of cognitive and SPECT scores during this period was compared between groups, and baseline data between converters and non-converters. The 15-OT was the only measure of progression that differed between the three groups; worsening scores on 15-OT were associated with worsening in verbal and visual retention, and decreased perfusion on left postsubicular area. In the MCI patients, cerebral perfusion fell over the two years in medial-posterior cingulate and fronto-temporo-parietal regions; AD showed extensive changes involving almost all cerebral regions. No SPECT changes were detected in controls. At baseline, the MCI patients who developed AD differed from non-converters in verbal recognition memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to provide a potential measure to differentiate between normal aging, MCI, and AD. Worsening on 15-OT was related to decreased perfusion in postsubicular area; but further longitudinal studies are needed to determine the contribution of 15-OT as a predictor of AD from MCI.

Although memory deficits are typically the earliest and most profound symptoms of Alzheimer’s disease (AD) and mild cognitive impairment (MCI), there is increasing recognition of subtle executive dysfunctions in these patients. The purpose of the present study was to determine the sensitivity of the Behavioral Assessment of the Dysexecutive Syndrome (BADS), and to detect early specific signs of the dysexecutive syndrome in the transition from normal cognition to dementia. The BADS was administered to 50 MCI subjects, 50 mild AD patients, and 50 normal controls. Statistically significant differences were found among the three groups with the AD patients performing most poorly, and the MCI subjects performing between controls and AD patients. The Rule Shift Cards and the Action Program subtests were the most highly discriminative between MCI and controls; the Zoo Map and Modified Six Elements between MCI and AD; and the Action Program, Zoo Map, and Modified Six Elements between AD and controls. These results demonstrate that the BADS is clinically useful in discriminating between normal cognition and progressive neurodegenerative conditions. Furthermore, these data confirm the presence of a dysexecutive syndrome even in mildly impaired elderly subjects. (JINS, 2009, 15, 751–757.)

Background: Despite evidence of dual diagnosis (DD) in impaired physicians, few studies have investigated its prevalence and clinical characteristics. Aims: To assess the prevalence and clinical characteristics of DD in a sample of inpatient physicians and to compare physician patients with DD to other inpatient physicians. Methods: A chart review of clinical and demographic data was conducted on 290 consecutive admissions to the inpatient unit of the Integrated Care Programme for Physicians in Barcelona from January 1999 to August 2005. Results: 60 (20.6%) patients had DD, with the most common form of co-occurring disorders being alcohol dependence with mood disorder (46.4%). DD patients were more likely to be male. DD patients were more similar to patients with substance use disorders with regards to demographic variables and antisocial personality traits, but were more similar to patients with only a psychiatric disorder concerning severity and avoidant traits. Conclusions: DD is a major cause of impai...

Working memory (WM) has hardly been explored in non-psychotic relatives of schizophrenic patients despite its potential suitability as a neurocognitive endophenotype. Indeed, WM modalities, components and processes have rarely been compared in the same group of relatives. The present study examined neurocognitive performance in healthy siblings of schizophrenic patients, including both spatial and verbal WM modalities and tests tapping maintenance (Spatial Span Backwards and CPT-IP d ′) and manipulative (Letters and Numbers Sequencing) WM processes. Methods 68 schizophrenia patients, 38 healthy siblings and 63 controls were assessed on IQ, attention, memory, WM, and executive functions. Cluster A symptoms were screened out in siblings and controls. Results Siblings had an intermediate performance between that of schizophrenic patients and controls. They performed worse than controls on IQ, LNS, animal naming, backwards spatial span, phonemic fluency, numbers d ′, and forward spatial span. Discussion Consistent with the WM literature in schizophrenia, both verbal and spatial WM differed significantly between siblings and controls, suggesting that WM deficits are modality independent. Our results failed to support the hypothesis that tests tapping WM manipulative processes heavily loading on DLFPC are quantitatively more impaired in relatives and, therefore, more sensitive to liability for schizophrenia. However, firm conclusions cannot be drawn until more studies assessing both maintenance and manipulative WM processes in relatives are available.

BACKGROUND Subjective memory impairment (SMI) refers to subjective awareness of initial memory decline undetectable with existing standardized cognitive tests. The Face Name Associative Memory Exam (FNAME) was created to detect memory deficits in individuals with preclinical Alzheimer's disease (AD). We reported normative data of a Spanish version of FNAME (S-FNAME) in cognitively normal (CN) Spanish-speaking subjects >49. OBJECTIVE To determine whether higher SMI [a modification of Memory Failures Everyday (MFE-30)] was related to worse memory performance (S-FNAME) or associated with greater affective symptoms in subjects >49; and whether MFE-30 and FNAME were able to discriminate between CN and mild cognitive impairment (MCI) subjects. METHODS 317 subjects (CN = 196, MCI = 121) were included in the analysis because they attended the annual "Open House Initiative" at Memory Clinic Fundacio ACE, were >49 years, literate, received S-FNAME, MFE-30, and Hospital Anxiety and Depression Scale, had Mini-Mental State Examination scores ≥27, and returned to complete a comprehensive diagnostic assessment. RESULTS MFE-30 scores were associated with affective symptoms but not with S-FNAME performance. S-FNAME scores were related to performance on memory variables of NBACE (neuropsychological battery used in Fundacio ACE). Although the MCI group showed significantly higher MFE-30 and worse S-FNAME scores than the CN group, their discriminability values were similar (Sensitivity: 49.6 versus 52.9; Specificity: 85.1 versus 83.6, respectively). CONCLUSIONS SMI was more related to depressive symptoms than to S-FNAME memory performance; and S-FNAME scores were related to other episodic memory test performances, but neither to affective symptoms nor to SMI. MFE-30 and S-FNAME are not optimal for discriminating between CN and MCI groups. Longitudinal follow-up will determine if lower S-FNAME and higher SMI are related to increased risk of AD.

BACKGROUND Psychiatrists are at a high risk of becoming mentally ill at some point during their careers. AIMS To compare the profile of psychiatrists admitted to the Barcelona Physicians' Health Programme (PHP) with other sick doctors in the programme. METHODS A retrospective case review of electronic medical records was conducted for physicians registered at the 'Colegio de Medicos' in Barcelona and consecutively admitted to the Barcelona PHP from January 1998 until December 2013. RESULTS One thousand two hundred eighteen records were reviewed. The 72 psychiatrists admitted to the programme were not statistically different from the other physicians in gender (54% versus 51% women), primary diagnosis (34% non-substance use mental disorders versus 29% substance use disorders), prevalence of adjustment disorders and median length of their first treatment episode (9.0 versus 8.4 months). Psychiatrists were significantly older (mean age 53 versus 50 years; t = 2.12; P < 0.05), more frequently had inpatient treatment during their first treatment episode (17% versus 10%; χ (2) = 4.57, P < 0.05) and had more referred (rather than self-referred) admissions (22% versus 13%; χ (2) = 4.57, P < 0.05) than other physicians. However, only the type of referral played a significant role when considering the simultaneous effect of all relevant variables (Wald = 4.43; P < 0.05). CONCLUSIONS Psychiatrists with mental disorders may be more reluctant to ask for help from a PHP voluntarily than other physicians. Members of this professional group should be encouraged to seek help when affected by mental distress or addiction problems.

Subjective cognitive decline (SCD) has been proposed as a marker of neurodegeneration in cognitively normal elderly. This idea is supported by the growing evidence that SCD is associated with Alzheimer's disease (AD) biomarkers and increases the risk of future cognitive impairment. Nevertheless, this evidence is not complete, since other studies have not found these associations. This discrepancy could have a methodological basis. It is well known that across the broad spectrum of degenerative disease from healthy controls to dementia, the research setting affects key characteristics of the sample such as age, educational level, or family history of dementia. However, virtually no studies have specifically tested the influence of sampling and recruitment methods in SCD research. Population-based samples are less biased and therefore they probably are more suitable for the study of memory complaints as a symptom at the population level. On the other hand, the memory clinic setting could introduce a set of biases that make these patients more likely to develop cognitive impairment. Thus, memory clinic would be the most cost-effective context in which to study the phenomenology of SCD due to AD and eventually recruit patients for secondary prevention trials. However, this general hypothesis needs to be tested. Studies that compare samples of patients with SCD from different settings are necessary. Sometimes it is difficult for patients with subtle forms of cognitive impairment to access specialized diagnostic centers. Based in our experience we state that Open House type initiatives may be useful for attracting these individuals to memory clinics.