Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer's type.

Alzheimer's disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer's disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer's type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging. We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer's type. Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer's type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-ß 42 (Aß42), phospho-tau 181 (P-tau181) and total tau (T-tau) for conversion to dementia of the Alzheimer's type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aß42, but normal P-tau181 and T-tau, and in mild cognitive impairment patients with abnormal Aß42, P-tau181 and T-tau. MMP-10 was correlated with age in subjects with normal Aß42, P-tau181 and T-tau levels. Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer's type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation.

Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment.

In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aß and p-tau-mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre-screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma extracellular vesicles (pEVs) are gaining popularity as a new source of biomarkers for the early stages of AD development. To identify an exosome proteomics signature linked to prodromal AD, we performed a cross-sectional study in a cohort of early-onset MCI (EOMCI) patients in which 184 biomarkers were measured in pEVs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink© proteomics. The obtained results showed that proteins measured in pEVs from EOMCI patients with established amyloidosis correlated with CSF p-tau181 levels, brain ventricle volume changes, brain hyperintensities, and MMSE scores. In addition, the correlations of pEVs proteins with different parameters distinguished between EOMCI Aß( +) and Aß(-) patients, whereas the CSF or plasma proteome did not. In conclusion, our findings suggest that pEVs may be able to provide information regarding the initial amyloidotic changes of AD. Circulating exosomes may acquire a pathological protein signature of AD before raw plasma, becoming potential biomarkers for identifying subjects at the earliest stages of AD development.

Correlations between the NMR Lipoprotein Profile, APOE Genotype, and Cholesterol Efflux Capacity of Fasting Plasma from Cognitively Healthy Elderly Adults.

Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer's disease. The inactivation of the APOE locus in mouse models supports the idea that it is involved in determining the CEC. With that in mind, we examine the impact of the plasma metabolome profile and the APOE genotype on the CEC in cognitively healthy elderly subjects. The study subjects were 144 unrelated healthy individuals. The plasma CEC was determined by exposing cultured mouse macrophages treated with BODIPY-cholesterol to human plasma. The metabolome profile was determined using NMR techniques. Multiple regression was performed to identify the most important predictors of CEC, as well as the NMR features most strongly associated with the APOE genotype. Plasma 3-hydroxybutyrate was the variable most strongly correlated with the CEC (r = 0.365; p = 7.3 × 10-6). Male sex was associated with a stronger CEC (r = -0.326, p = 6.8 × 10-5). Most of the NMR particles associated with the CEC did not correlate with the APOE genotype. The NMR metabolomics results confirmed the APOE genotype to have a huge effect on the concentration of plasma lipoprotein particles as well as those of other molecules including omega-3 fatty acids. In conclusion, the CEC of human plasma was associated with ketone body concentration, sex, and (to a lesser extent) the other features of the plasma lipoprotein profile. The APOE genotype exerted only a weak effect on the CEC via the modulation of the lipoprotein profile. The APOE locus was associated with omega-3 fatty acid levels independent of the plasma cholesterol level.

The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment.

Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients.

Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer's Disease Aetiopathogenesis in Men.

Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer's disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomisation to construct an age-independent mLOY polygenic risk score (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per standard deviation unit (p = 4.22 × 10-20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in men with mild cognitive impairment (hazard ratio (HR) = 1.23, p = 0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group, suggesting that these associations are caused by the inherent loss of the Y chromosome. Additionally, the blood mLOY phenotype in men was associated with increased cerebrospinal fluid levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis.

Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease.

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, 5445 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.

A comparison of medically serious suicide attempters admitted to intensive care units versus other medically serious suicide attempters.

BACKGROUND: Medically serious suicide attempts (MSSA) represent a subgroup of clinically heterogeneous suicidal behaviours very close to deaths by suicide. A simple definition of an MSSA is a suicide attempt with life-threatening consequences, regardless of the severity of the attempter's mental disorder. Few studies have specifically analysed the heterogeneity of MSSA. Therefore, the aim of this study is to describe the profile of individuals who made a highly severe MSSA and to compare those admitted to Intensive Care Units (ICU) - including Burn Units- with other MSSA admitted to other medical and surgical units. METHODS: The study sample consisted of 168 patients consecutively admitted to non-psychiatric wards from two public hospitals in Barcelona after an MSSA during a 3-year period. In order to select more severe MSSA, the minimum hospital stay was expanded from Beautrais' definition of ≥ 24 h to ≥ 48 h. Mean hospital stay was 23.68 (SD = 41.14) days. Patients needing ICU treatment (n = 99) were compared to other MSSArs (n = 69) that were admitted to other medical and surgical units, not requiring intensive care treatment, with an initial bivariant analysis followed by a logistic regression analysis using conditional entrance. RESULTS: Medically serious suicide attempters (MSSArs) spent more time hospitalized, more frequently reported recent stressful life events, were more likely to have at least one prior suicide attempt (SA) and their current attempt was more frequently non-planned, compared to the profile of MSSArs reported in previous studies. The most frequent method was medication overdose (67.3%) and jumping from heights (23.2%). Among those who chose more than one method (37.6%), the most frequent combination was medication overdose and drug use. Affective disorders and personality disorders were the most frequent diagnoses. Higher educational level, history of previous mental disorders and prior lifetime suicide attempts were significantly more frequent among those admitted to ICU compared to other MSSArs. Patients needing admission to ICU less frequently used self-poisoning and cuts. CONCLUSIONS: MSSA needing ICU admission can be regarded clinically as similar to attempts resulting in suicide. More research on this type of highly severe suicide behaviour is needed due to its serious implications both from a clinical and public health perspective.

Nurse admissions at a specialized mental health programme: A pre-Covid-19 retrospective review (2000-2019).

AIMS: Nursing is a stressful and emotionally demanding profession. To date, few mental health treatment interventions have been developed for them worldwide. This study aims to explore referral trends in nurses with mental disorders admitted to a pioneer specialized mental health programme in Europe from 2000 to 2019. DESIGN: A retrospective observational study of 1297 medical e-records of nurses with mental health disorders admitted to the Galatea Care Programme in Barcelona was conducted. METHODS: Three periods were analysed: 2000-2006, 2007-2012 and 2013-2019. Socio-demographic and clinical variables were compared. Diagnoses followed Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria. RESULTS: Gender and age at referral did not change over time. Self-referrals grew from 85.1% in the first period to 95.3% in the last period; inpatient admissions decreased from 24.1% to 18.2%, although this was not significant; nurses were less frequently on sick leave on admission over time (59.1% vs. 45.7%); they were more likely to have a temporary contract in the second period (9.5% vs. 4.8% and 4%) and prevalence of main diagnosis changed with a considerable decrease in affective and substance use disorders after 2006 and a progressive increase in adjustment disorders during the whole period. CONCLUSION: Free, voluntary, highly confidential programmes for nurses with mental disorders may enhance voluntary and earlier help seeking. These findings can be considered when implementing specialized interventions for them in other settings. WHAT PROBLEM DID THE STUDY ADDRESS?: Nursing is a stressful and emotionally demanding profession. To date, few specialized mental health services have been developed for them worldwide. This study aims to explore referral trends in nurses with mental disorders admitted to a pioneer programme in Europe, the Galatea Care Programme in Barcelona, from 2000 to 2019. WHAT WERE THE MAIN FINDINGS?: The number of referrals to the programme grew especially after the first 7-year period. Admissions were more likely to be voluntary during the last period. Prevalence of substance use disorders at admission dropped steadily while prevalence of adjustment disorders progressively increased over the two decades. Nurses were also less likely to be on sick leave at admission. WHERE AND ON WHOM WILL THE RESEARCH HAVE IMPACT?: Free, voluntary, highly confidential programmes for nurses with mental disorders may enhance voluntary and earlier help seeking. These findings can be considered when implementing specialized interventions for them in other settings.

Complementary pre-screening strategies to uncover hidden prodromal and mild Alzheimer's disease: Results from the MOPEAD project.

INTRODUCTION: The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis. METHODS: Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care-based protocol for early detection of cognitive decline (PC), and (4) a tertiary care-based pre-screening at diabetologist clinics (DC). RESULTS: A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC). CONCLUSION: These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD.

Establishing In-House Cutoffs of CSF Alzheimer's Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort.

BACKGROUND: Clinical diagnosis of Alzheimer's disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. METHODS: We quantified CSF Aß1-42, Aß1-40, t-Tau, and p181Tau with standard INNOTEST® ELISA and Lumipulse G® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer's disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aß1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aß1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aß1-42/Aß1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). RESULTS: Cutoff values of Aß1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aß1-40 and 0.96 for p181TAU. Passing-Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aß1-40. Bland-Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aß1-42/Aß1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan-Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815-27). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. CONCLUSIONS: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.

PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment.

A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer's disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau181, total tau, and Aß1-42 was assessed in 1261 MCI patients. We found that MCI patients who carried the p.P522R variant showed a slower rate of cognitive decline compared to non-carriers and that this effect was mediated by lower pTau181 levels in CSF. The effect size of the association of p.P522R with the cognitive decline and pTau181 was similar to that of APOE-ε4, the strongest genetic risk factor for AD. Interestingly, the protective effect of p.P522R was more pronounced in MCI patients with low Aß1-42 levels suggesting a role of PLCG2 in the response to amyloid pathology. In line with this hypothesis, we observed no protective effect of the PLCG2 variant on the cognitive decline in population-based studies probably due to the lower prevalence of amyloid positivity in these samples compared to MCI patients. Concerning the potential biological underpinnings, we identified a network of co-expressed proteins connecting PLCG2 to APOE and TREM2 using unsupervised co-regulatory network analysis. The network was highly enriched for the complement cascade and genes differentially expressed in disease-associated microglia. Our data show that p.P522R in PLCG2 reduces AD disease progression by mitigating tau pathology in the presence of amyloid pathology and, as a consequence, maintains cognitive function. Targeting the enzyme PLCG2 might provide a new therapeutic approach for treating AD.

Family physicians with mental disorders admitted to a physicians' health programme: what can be learned?

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.

Integral Treatment Programme for Addicted Physicians: Results from The Galatea Care Programme for Sick Physicians.

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.

The MOPEAD project: Advancing patient engagement for the detection of "hidden" undiagnosed cases of Alzheimer's disease in the community.

In most, if not all health systems, dementia is underdiagnosed, and when diagnosis occurs, it is typically at a relatively late stage in the disease process despite mounting evidence showing that a timely diagnosis would result in numerous benefits for patients, families, and society. Moving toward earlier diagnoses in Alzheimer's disease (AD) requires a conscientious and collective effort to implement a global strategy addressing the multiple causes hindering patient engagement at different levels of society. This article describes the design of the Models of Patient Engagement for Alzheimer's Disease project, an ongoing EU-funded public-private multinational initiative that will compare four innovative patient engagement strategies across five European countries regarding their ability to identify individuals with prodromal AD and mild AD dementia, which are "hidden" in their communities and traditionally not found in the typical memory clinic setting. The strategies include an online AD citizen science platform, an open house initiative at the memory clinics, and patient engagement at primary care and diabetologist clinics.

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.

Exploring APOE genotype effects on Alzheimer's disease risk and amyloid ß burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results.

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) ε4'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 ε4 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 ε4 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.

Psychometric Properties and Normative Data of the Zuckerman-Kuhlman Personality Questionnaire in a Psychiatric Outpatient Sample.

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.

Borderline Personality Disorder and Personality Inventory for DSM-5 (PID-5): Dimensional personality assessment with DSM-5.

INTRODUCTION: Borderline personality disorder (BPD) diagnosis has been considered highly controversial. The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) proposes an alternative hybrid diagnostic model for personality disorders (PD), and the Personality Inventory for DSM-5 (PID-5) has adequate psychometric properties and has been widely used for the assessment of the dimensional component. METHODS: Our aim was to analyze the utility of the personality traits presented in Section III of the DSM-5 for BPD diagnosis in an outpatient clinical sample, using the Spanish version of the PID-5. Two clinical samples were studied: BPD sample (n=84) and non-BPD sample (n=45). Between-sample differences in PID-5 scores were analyzed. RESULTS: The BPD sample obtained significantly higher scores in most PID-5 trait facets and domains. Specifically and after regression logistic analyses, in BPD patients, the domains of Negative Affectivity and Disinhibition, and the trait facets of emotional lability, [lack of] restricted affectivity, and impulsivity were more significantly associated with BPD. CONCLUSIONS: Although our findings are only partially consistent with the algorithm proposed by DSM-5, we consider that the combination of the PID-5 trait domains and facets could be useful for BPD dimensional diagnosis, and could further our understanding of BPD diagnosis complexity.

Impulsive clinical profile of Borderline Personality Disorder with comorbid Substance Use Disorder.

INTRODUCTION: Borderline Personality Disorder (BPD) is one of the Personality Disorder most frequently associated with Substance Use Disorder (SUD). According to different models, the Behavioral dysregulation-BPD subgroup has a higher prevalence of SUD and certain impulsivity behaviors than the other two subgroups. METHODS: Out of 156 BPD patients, 47 were in the Behavioral dysregulation-BPD subgroup, 55 in Affective dysregulation, and 54 in Disturbed relatedness. All patients completed the SCID-II for DSM-IV Axis II Disorders, SCID-I for DSM-IV Axis I Disorders, Barratt Impulsiveness Scale (BIS-11) and Revised Diagnostic Interview for Borderlines (DIB-R). RESULTS: In the comparison of the BPD subgroups, Behavioral dysregulation showed significantly more prevalence of SUD (alcohol and cocaine), and tendency for anxiolytics, higher impulsivity (DIB-R, but none in BIS-11), and higher number of suicide attempts and psychiatric admissions, although these was not significant in comparison with the other subgroups. CONCLUSIONS: This should be especially useful in the discrimination of BPD patients for different therapeutic approaches and prognoses.

Study of prevalence of Personality Disorders in inmate men sample with Substance Use Disorders using of PDQ-4+ Self-Report.

INTRODUCTION: The study focused on examining the prevalence of Personality Disorders (PD) in 51 male inmates diagnosed with Substance Use Disorders (SUDs) lifetime within a specialized unit at a prison. METHODS: The instruments administered included the Structured Clinical Interview for DSM-IV Axis I and the Personality Diagnostic Questionnaire-4+. RESULTS: The type of crime most frequently committed by the incarcerated was the robbery (76.5%), including robbery with violence. 45.1% of the patients screened positive for Antisocial PD, followed by 35.3% for Paranoid and 23.5% for Obsessive Compulsive PD. The results reflect a male inmate sample exhibiting a clinical profile characterized by SUDs and PD, with almost half of the total sample presenting Antisocial PD. CONCLUSIONS: The presence of Antisocial and Paranoid PD with SUD suggests a more complex personality profile, with a tendency to carry out more aggressive crimes, including robbery with violence. A more comprehensive PD assessment should be carried out in prison settings in order to identify dangerous individuals who are at risk of recidivism.