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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.

BackgroundTo explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aβ) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD).MethodsTwo hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI),18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables.ResultsAdjusted multiple linear regression models showed that FreeSurfer (B − .245; 95% CI − .1.676, − .393,p = .016) and β burden (SUVR) (B − .180; 95% CI − 2.140, − .292;p = .070) were associated with face–name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p = .070). There was non-significant interaction of these two factors on this same CCs domain score (p = .54). However, its cumulative effects on face–name associative performance indicated that those individuals with either higher WMH load or higher Aβ burden showed the worst performance on the face–name associative memory CCs domain score.ConclusionsOur results suggest that increased WMH load and increased Aβ are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention.

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.

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.

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.

Background Alzheimer disease (AD) is a progressive neurodegenerative disorder affecting the elderly with a prevalence of 7.1% in women and 3.3% in men. Sex-related patterns have been reported in prognosis, biomarker status, and risk factors. Despite this, the interaction of sex has received limited attention, with AD trials persistently recruiting lower numbers of women than the population distribution and a lack of information on the sex-disaggregated effects of anti-dementia therapies. This is the first study aiming to identify the role of sex in the selection for screening in AD clinical trials. Methods This cross-sectional study provides a comprehensive analysis of screening eligibility according to a set of pre-selection criteria currently applied at Fundació ACE memory clinic for a more efficient trial screening process. A cohort of 6667 women and 2926 men diagnosed with AD dementia (55%) or mild cognitive impairment (45%) was analyzed. We also assessed the frequencies of men and women effectively screened for trial enrolment over a period of 10 years. Additionally, data from AddNeuroMed study was used to explore trends in eligibility based on the education criteria. Results Women showed a significantly lower chance of being eligible for screening than men (OR = 1.26; p < 0.01). This imbalance was confirmed by a lower frequency of women screened for enrolment compared to the study population (63.0% vs. 69.5%). Education was revealed as the key criterion contributing to this unbalance, with men showing over twice the chance of being screened compared with women (OR = 2.25, p < 0.01). Education-based differences were greater in earlier born patients, but the gap narrowed and achieved balance with increasing year of birth. This observation was replicated using data from other European populations included in AddNeuroMed study. Comorbidity was the most limiting criterion with sex differences in frequencies and significant discrimination against the selection of men (OR = 0.86, p < 0.01). Conclusions The large number of low-educated elderly women with AD demands for a sex-focused approach in clinical research. New assessment tools insensitive to education level should be developed to enable a proportional representation of women. Although this gender education gap is mostly inexistent in developed countries, economic or cultural factors may lead to different scenarios in other regions. Overlooking the impact of sex may lead to a handicap in AD research with a direct adverse impact on women’s health.

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.

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD+P). AD+P affects ∼50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD-P). Although the estimated heritability of AD+P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5,445 AD+P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p=1.26×10−8) and one spanning the 3’-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p=3.24×10−8), had genome-wide significant associations with AD+P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD+P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD+P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture.

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.

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.

BACKGROUND Recruitment methods can determine sample characteristics in mild cognitive impairment and Alzheimer's disease dementia, but little is known about its influence in subjective cognitive decline (SCD). OBJECTIVE To determine the influence of two types of recruitment methods in the characteristics of individuals with SCD. METHODS We select and compare clinical and neuropsychological features, and frequency of APOE ɛ4 allele of 326 subjects with SCD from two cohorts: Open House Initiative (OHI) versus Memory Unit (MU). A logistic regression analysis (LRA), using gender and years of education as covariates, was used to examine the neuropsychological variables. RESULTS The OHI sample were mostly women (75.9% versus 64.5%, p

Individuals with subjective cognitive decline (SCD) have the perception of memory problems without showing impairment on standardized cognitive tests. SCD has been associated with an increased risk of developing Alzheimer’s disease (AD). Neuroticism and openness personality dimensions have also been associated with SCD and AD. From the aforementioned, we aimed to ascertain whether the dimensions and traits defined by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) differentiate between individuals with SCD and the general population (GP). A total of 187 participants with SCD and mild affective symptomatology recruited from the Fundació ACE Health Brain Initiative (FACEHBI) project completed the ZKPQ. Each SCD participant was matched by sex and age to an individual from the GP. Both samples included 71 men and 116 women with a mean age of 65.9 years. Results indicated that the SCD group scored significantly lower in Neuroticism-Anxiety and Activity than the GP group. Only Activity remained statistically significant in a multivariate analysis. These findings suggest that individuals with SCD have a low energy level and a dislike for an active and busy life. From the obtained results and knowing additional physical activities may delay the conversion from normal aging to cognitive impairment, we encourage promoting this lifestyle in daily routine. The assessment of personality may result in an SCD plus feature, which may serve as an upgrading strategy for future research.

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.

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 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: 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.

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.

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: Long-term longitudinal studies with multimodal biomarkers are needed to delve into the knowledge of preclinical AD. Subjective cognitive decline has been proposed as a risk factor for the development of cognitive impairment. Thus, including individuals with SCD in observational studies may be a cost-effective strategy to increase the prevalence of preclinical AD in the sample. Objectives: To describe the rationale, research protocols and baseline characteristics of participants in the Fundació ACE Healthy Brain Initiative (FACEHBI). Design: FACEHBI is a clinical trial (EudraCT: 2014-000798-38) embedded within a long-term observational study of individuals with SCD. Setting: Participants have been recruited at the memory clinic of Fundació ACE (Barcelona) from two different sources: patients referred by a general practitioner and individuals from an Open House Initiative. Participants: 200 individuals diagnosed with SCD with a strictly normal performance in a comprehensive neuropsychological battery. Measurements: Individuals will undergo an extensive neuropsychological protocol, risk factor assessment and a set of multimodal biomarkers including florbetaben PET, structural and functional MRI, diffusion tensor imaging, determination of amyloid species in plasma and neurophthalmologic assessment with optical coherence tomography. Results: Two hundred individuals have been recruited in 15 months. Mean age was 65.9 years; mean MMSE was 29.2 with a mean of 14.8 years of education. Conclusions: FACEHBI is a long-term study of cognition, biomarkers and lifestyle that has been designed upon an innovative symptom-based approach using SCD as target population. It will shed light on the pathophysiology of preclinical AD and the role of SCD as a risk marker for the development of cognitive impairment.

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.

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.

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.

The aim of the present study was to assess the efficacy of psychoeducation as compared with cognitive behavioral group therapy in adults with attention deficit hyperactivity disorder (ADHD) who still had significant symptoms and were in pharmacological treatment. This is the first study on psychoeducation in adults with ADHD. Thirty-two individuals were randomized to two treatment conditions: 15 were in the psychoeducation group and 11 were in the cognitive behavioral group therapy. A total of 30 completed treatment, and 26 completed the follow-up assessments. The results indicated that both treatments were associated with statistically significant improvements on inattention, hyperactivity, impulsivity, and self-esteem. The patients in both groups showed a decrease in anxiety symptoms and obtained significantly lower scores in depression. Measures on functional impairment showed statistically significant differences on improved quality of life and on lower global severity as perceived in self-report and assessed by clinician report. Psychoeducation demonstrated to be an effective treatment in reducing ADHD core symptoms.

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.

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.

There is an increasing need for standardized assessment of cognition in older patients that is relatively brief, easy to administer, and has normative data adjusted for age and educational attainment. We tested 332 literate, cognitively normal, Spanish persons older than 49 years from the Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades (Barcelona, Spain) with measures of cognitive information processing speed, orientation, attention, verbal learning and memory, language, visuoperception, praxis, and executive functions. Several of the tests were affected by age, education, and/or gender, but the language of administration (i.e., Spanish or Catalan) did not affect the test scores. Standardized scores and percentile ranks were calculated for each age and/or education group for use by clinical neuropsychologists.

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...

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.

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.

Researchers have begun to study the pharmacologic properties of medications in different ethnic minority groups and national populations. In this context, delimitation of the ethnic or national category is essential to ensure sufficient cultural and genetic homogeneity to render the study meaningful. In Spain, the ''Latino'' population tends to have its origins in the Andean region of South America. There is some evidence that there is genetic variation in isoenzymes CYP2D6 and CYP1A2 1 in Amerindians, which impacts the gene that encodes the serotonin transporter, 1,2 which would appear to impact the metabolism of SSRI drugs but much less so dual-acting drugs such as duloxetine.