Sociocultural factors, guilt and depression in family caregivers of people with dementia. Kinship differences.

OBJECTIVES: This study aims to analyze the role that family obligations and social desirability have for understanding guilt and depressive symptoms in family caregivers. A theoretical model is proposed to analyze this significance based on the kinship with the person cared for. METHODS: Participants are 284 family caregivers of people with dementia divided into four kinship groups (husbands, wives, daughters and sons). Face-to-face interviews were conducted assessing sociodemographic variables, familism (family obligations), dysfunctional thoughts, social desirability, frequency and discomfort associated with problematic behaviors, guilt and depressive symptoms. Path analyses are performed to analyze the fit of the proposed model and multigroup analysis to study potential differences between kinship groups. RESULTS: The proposed model fits the data well and explains significant percentages of variance of guilt feelings and depressive symptomatology for each group. The multigroup analysis suggests that, for daughters, higher family obligations were associated with depressive symptomatology through a report of higher dysfunctional thoughts. For daughters and wives, an indirect association between social desirability and guilt was observed through reaction to problematic behaviors. CONCLUSION: The results support the need to consider the significance of sociocultural aspects such as family obligations and the desirability bias in the design and implementation of interventions for caregivers, especially for daughters. Considering that the variables that contribute to explaining caregivers' distress vary depending on the relationship with the person cared for, individualized interventions may be warranted depending on the kinship group.

Cross-cultural analysis of the role of ambivalent feelings for understanding caregivers' depressive symptoms.

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are considered to cause ambivalent feelings in caregivers that may contribute to understanding their depressive symptoms. Transnational research is needed in order to increase our knowledge about the cross-cultural equivalence of theoretical models to understand caregivers' mental health. The aim of this study was to cross-culturally analyze the association between BPSD, ambivalent feelings and depressive symptoms in two samples of family caregivers of people with dementia from Spain and the UK. METHODS: Participants in this study were 432 caregivers who completed measures of BPSD, ambivalent feelings and depressive symptoms. The association between the assessed variables was tested through path-analysis, with differences between countries tested through multigroup analysis. RESULTS: The results suggest that the influence of BPSD on caregivers' depressive symptoms is indirect, through ambivalent feelings. The observed associations were equivalent between countries and explained a significant percentage of the variance of depressive symptoms. CONCLUSION: The findings of this study provide, for the first time, evidence of equivalent cross-cultural paths analyzing the role of ambivalent feelings for understanding caregivers' depressive symptoms. The practical implications of these results are discussed.

External quality assessment of orthohantavirus and lymphocytic choriomeningitis virus molecular detection and serology in Europe, 2021.

BackgroundRodent-borne viruses such as orthohantaviruses and arenaviruses cause considerable disease burden with regional and temporal differences in incidence and clinical awareness. Therefore, it is important to regularly evaluate laboratory diagnostic capabilities, e.g. by external quality assessments (EQA).AimWe wished to evaluate the performance and diagnostic capability of European expert laboratories to detect orthohantaviruses and lymphocytic choriomeningitis virus (LCMV) and human antibody response towards orthohantaviruses.MethodsWe conducted an EQA in 2021; molecular panels consisted of 12 samples, including different orthohantaviruses (Seoul, Dobrava-Belgrade (DOBV), Puumala (PUUV) and Hantaan orthohantavirus), LCMV and negative controls. Serological panels consisted of six human serum samples reactive to PUUV, DOBV or negative to orthohantaviruses. The EQA was sent to 25 laboratories in 20 countries.ResultsThe accuracy of molecular detection of orthohantaviruses varied (50‒67%, average 62%) among 16 participating laboratories, while LCMV samples were successfully detected in all 11 participating laboratories (91-100%, average 96%). The accuracy of serological diagnosis of acute and past orthohantavirus infections was on average 95% among 20 participating laboratories and 82% in 19 laboratories, respectively. A variety of methods was used, with predominance of in-house assays for molecular tests, and commercial assays for serological ones.ConclusionSerology, the most common tool to diagnose acute orthohantavirus infections, had a high accuracy in this EQA. The molecular detection of orthohantaviruses needs improvement while LCMV detection (performed in fewer laboratories) had 95% accuracy. Further EQAs are recommended to be performed periodically to monitor improvements and challenges in the diagnostics of rodent-borne diseases.

Family caregivers of people with dementia in the context of the sociocultural stress and coping model: An examination of gender differences.

The study assessed gender differences in the associations between familism dimensions, dysfunctional thoughts, and resource and outcome variables in 190 Spanish dementia family caregivers. A theoretical model was tested through path analysis, obtaining an excellent fit of the model to the data. Higher scores in the familial obligations dimension were associated with lower self-efficacy for self-care and obtaining respite and leisure frequency, and higher anxious and depressive feelings, in female caregivers only. Significant between-gender differences were obtained, suggesting that female caregivers holding strong familistic values are more vulnerable to the negative consequences of caregiving compared to male caregivers.

Duration of Protection After Vaccination Against Yellow Fever: A Systematic Review and Meta-Analysis.

The duration of protection after a single dose of yellow fever vaccine is a matter of debate. To summarize the current knowledge, we performed a systematic literature review and meta-analysis. Studies on the duration of protection after 1 and ≥2 vaccine doses were reviewed. Data were stratified by time since vaccination. In our meta-analysis, we used random-effects models. We identified 36 studies from 20 countries, comprising more than 17 000 participants aged 6 months to 85 years. Among healthy adults and children, pooled seroprotection rates after single vaccination dose were close to 100% by 3 months and remained high in adults for 5 to 10 years. In children vaccinated before age 2 years, the seroprotection rate was 52% within 5 years after primary vaccination. For immunodeficient persons, data indicate relevant waning. The extent of waning of seroprotection after yellow fever vaccination depends on age and immune status at primary vaccination.

Caring for Relatives with Dementia in Times of COVID-19: Impact on Caregivers and Care-recipients.

OBJECTIVES: To analyze caregivers' perceived impact of the pandemic in their mental health and the well-being of the care-recipients. METHODS: Caregivers (N = 88) were asked if they had COVID-19 and about their perceptions of change of care-recipients' health conditions as well as whether their own mental health, conflicts with care-recipients and other relatives, thoughts of giving up caregiving, and feelings of coping well with the situation. RESULTS: A large percentage of caregivers perceived a worsening of care-recipients' symptoms and of their own negative emotions, an increase in the number of conflicts and thoughts of needing to give up caregiving. Having had COVID-19 and reporting higher levels of distress as well as giving up caregiving were related to perceived worsening in care-recipients well-being. Perceived increases were mainly reported by younger caregivers, those who perceived to have not coped well, and those reporting an increase in conflicts. Some caregivers perceived an increase in positive emotions. CONCLUSIONS: The pandemic has a negative impact on caregivers' perceptions about the course of their own emotions and care-recipients' well-being. CLINICAL IMPLICATIONS: Interventions are needed to train caregivers in strategies to cope with the sources of stress caused by the pandemic and to promote social support.

Resource-efficient internally controlled in-house real-time PCR detection of SARS-CoV-2.

BACKGROUND: The reliable detection of SARS-CoV-2 has become one of the most important contributions to COVID-19 crisis management. With the publication of the first sequences of SARS-CoV-2, several diagnostic PCR assays have been developed and published. In addition to in-house assays the market was flooded with numerous commercially available ready-to-use PCR kits, with both approaches showing alarming shortages in reagent supply. AIM: Here we present a resource-efficient in-house protocol for the PCR detection of SARS-CoV-2 RNA in patient specimens (RKI/ZBS1 SARS-CoV-2 protocol). METHODS: Two duplex one-step real-time RT-PCR assays are run simultaneously and provide information on two different SARS-CoV-2 genomic regions. Each one is duplexed with a control that either indicates potential PCR inhibition or proves the successful extraction of nucleic acid from the clinical specimen. RESULTS: Limit of RNA detection for both SARS-CoV-2 assays is below 10 genomes per reaction. The protocol enables testing specimens in duplicate across the two different SARS-CoV-2 PCR assays, saving reagents by increasing testing capacity. The protocol can be run on various PCR cyclers with several PCR master mix kits. CONCLUSION: The presented RKI/ZBS1 SARS-CoV-2 protocol represents a cost-effective alternative in times of shortages when commercially available ready-to-use kits may not be available or affordable.

Travel-associated neurological disease terminated in a postmortem diagnosed atypical HSV-1 encephalitis after high-dose steroid therapy - a case report.

BACKGROUND: Human encephalitis can originate from a variety of different aetiologies, of which infection is the most common one. The diagnostic work-up is specifically challenging in patients with travel history since a broader spectrum of unfamiliar additional infectious agents, e. g. tropical disease pathogens, needs to be considered. Here we present a case of encephalitis of unclear aetiology in a female traveller returning from Africa, who in addition developed an atypical herpes simplex virus (HSV) encephalitis in close temporal relation with high-dose steroid treatment. CASE PRESENTATION: A previously healthy 48-year-old female presented with confusion syndrome and impaired vigilance which had developed during a six-day trip to The Gambia. The condition rapidly worsened to a comatose state. Extensive search for infectious agents including a variety of tropical disease pathogens was unsuccessful. As encephalitic signs persisted despite of calculated antimicrobial and antiviral therapy, high-dose corticosteroids were applied intravenously based on the working diagnosis of an autoimmune encephalitis. The treatment did, however, not improve the patient's condition. Four days later, bihemispheric signal amplification in the insular and frontobasal cortex was observed on magnetic resonance imaging (MRI). The intracranial pressure rapidly increased and could not be controlled by conservative treatment. The patient died due to tonsillar herniation 21 days after onset of symptoms. Histological examination of postmortem brain tissue demonstrated a generalized lymphocytic meningoencephalitis. Immunohistochemical reactions against HSV-1/2 indicated an atypical manifestation of herpesviral encephalitis in brain tissue. Moreover, HSV-1 DNA was detected by a next-generation sequencing (NGS) metagenomics approach. Retrospective analysis of cerebrospinal fluid (CSF) and serum samples revealed HSV-1 DNA only in specimens one day ante mortem. CONCLUSIONS: This case shows that standard high-dose steroid therapy can contribute to or possibly even trigger fulminant cerebral HSV reactivation in a critically ill patient. Thus, even if extensive laboratory diagnostics including wide-ranging search for infectious pathogens has been performed before and remained without results, continuous re-evaluation of potential differential diagnoses especially regarding opportunistic infections or reactivation of latent infections is of utmost importance, particularly if new symptoms occur.

[Efficacy of a multidisciplinary care management program for patients admitted at hospital because of heart failure (ProMIC)]. / Eficacia de un programa multidisciplinar de gestión de cuidados en pacientes que ingresan por insuficiencia cardiaca (ProMIC).

OBJECTIVE: To assess the efficacy of the ProMIC, multidisciplinary program for patients admitted at hospital because of heart failure (HF) programme, in reducing the HF-related readmission rate. DESING: Quasi-experimental research with control group. SETTINGS: Twelve primary health care centres and 3 hospitals from the Basque Country. PARTICIPANTS: Aged 40 years old or above patients admitted for HF with a New York Heart Association functional class II to IV. INTERVENTIONS: Patients in the intervention group carried out the ProMIC programme, a structured clinical intervention based on clinical guidelines and on the chronic care model. Control group received usual care. MAIN MEASUREMENTS: The rate of readmission for HF and health-related quality of life RESULTS: One hundred fifty five patients were included in ProMIC group and 129 in control group. 45 rehospitalisation due to heart failure happened in ProMIC versus 75 in control group (adjusted hazard ratio=0.59, CI 95%: 0.36-0.98; P=.049). There were significant differences in specific quality of life al 6 months. No significant differences were found in rehospitalisation due to all causes, due to cardiovascular causes, visits to emergency room, mortality, the combined variable of these events, the functional capacity or quality of life at 12 months of follow up. CONCLUSIONS: ProMIC reduces significantly heart failure rehospitalisation and improve quality of life al 6 months of follow up. No significant differences were found in the rests of variables.

Long-term Immune Response to Yellow Fever Vaccination in Human Immunodeficiency Virus (HIV)-Infected Individuals Depends on HIV RNA Suppression Status: Implications for Vaccination Schedule.

Background: In human immunodeficiency virus (HIV)-infected individuals, the immune response over time to yellow fever vaccination (YFV) and the necessity for booster vaccination are not well understood. Methods: We studied 247 participants of the Swiss HIV Cohort Study (SHCS) with a first YFV after HIV diagnosis and determined their immune responses at 1 year, 5 years, and 10 years postvaccination by yellow fever plaque reduction neutralization titers (PRNTs) in stored blood samples. A PRNT of 1:≥10 was regarded as reactive and protective. Predictors of vaccination response were analyzed with Poisson regression. Results: At vaccination, 82% of the vaccinees were taking combination antiretroviral therapy (cART), 83% had suppressed HIV RNA levels (<400 copies/mL), and their median CD4 T-cell count was 536 cells/µL. PRNT was reactive in 46% (95% confidence interval [CI], 38%-53%) before, 95% (95% CI, 91%-98%) within 1 year, 86% (95% CI, 79%-92%) at 5 years, and 75% (95% CI, 62%-85%) at 10 years postvaccination. In those with suppressed plasma HIV RNA at YFV, the proportion with reactive PRNTs remained high: 99% (95% CI, 95%-99.8%) within 1 year, 99% (95% CI, 92%-100%) at 5 years, and 100% (95% CI, 86%-100%) at 10 years. Conclusions: HIV-infected patients' long-term immune response up to 10 years to YFV is primarily dependent on the control of HIV replication at the time of vaccination. For those on successful cART, immune response up to 10 years is comparable to that of non-HIV-infected adults. We recommend a single YFV booster after 10 years for patients vaccinated on successful cART, whereas those vaccinated with uncontrolled HIV RNA may need an early booster.

Need for additional capacity and improved capability for molecular detection of yellow fever virus in European Expert Laboratories: External Quality Assessment, March 2018.

An external quality assessment of yellow fever virus (YFV) molecular detection in European laboratories was organised in rapid response to an increase in human cases in Brazil in 2018 with risk of import to Europe. Detection of YFV was assessed among 32 laboratories in 23/31 European Union (EU) and European Economic Area (EEA) countries and two laboratories in one non-EU/EEA country. Adequate capabilities were lacking in 10/23 countries; five did not participate as they lacked implemented assays.

Low Thymic Activity and Dendritic Cell Numbers Are Associated with the Immune Response to Primary Viral Infection in Elderly Humans.

Immunological competence declines progressively with age, resulting in increased susceptibility of the elderly to infection and impaired responses to vaccines. Underlying mechanisms remain largely obscure as they have been related to complex, individual systemic immune properties that are challenging to investigate. In this study, we explored age-related changes in human immunity during a primary virus infection experimentally induced by immunization with live-attenuated yellow fever (YF) vaccine. Applying detailed serology, advanced FACS analysis, and systems biology, we discovered that aged subjects developed fewer neutralizing Abs, mounted diminished YF-specific CD8(+) T cell responses, and showed quantitatively and qualitatively altered YF-specific CD4(+) T cell immunity. Among numerous immune signatures, low in vivo numbers of naive CD4(+) recent thymic emigrants and peripheral dendritic cells correlated well with reduced acute responsiveness and altered long-term persistence of human cellular immunity to YF vaccination. Hence, we reveal in this article that essential elements of immune responses such as recent thymic emigrants and dendritic cells strongly relate to productive immunity in the elderly, providing a conceivable explanation for diminished responsiveness to vaccination with neoantigens and infection with de novo pathogens in the aged population.

Key aspects related to implementation of risk stratification in health care systems-the ASSEHS study.

BACKGROUND: The lack of proven efficacy of new healthcare interventions represents a problem for health systems globally. It is partly related to suboptimal implementation processes, leading to poor adoption of new interventions. Activation of Stratification Strategies and Results of the interventions on frail patients of Healthcare Services (ASSEHS) EU project (N° 2013 12 04) aims to study current existing health Risk Stratification (RS) strategies and tools on frail elderly patients. This paper aims at identifying variables that make the implementation of population RS tools feasible in different healthcare services. METHODS: Two different methods have been used to identify the key elements in stratification implementation; i) a Scoping Review, in order to search and gather scientific evidence and ii) Semi-structured interviews with six key experts that had been actively involved in the design and/or implementation of RS strategies. It aims to focus the implementation construct on real-life contextual understandings, multi-level perspectives, and cultural influences. RESULTS: A Feasibility Framework has been drawn. Two dimensions impact the feasibility of RS: (i) Planning, deployment and change management and (ii) Care intervention. The former comprises communication, training and mutual learning, multidisciplinarity of the team, clinicians' engagement, operational plan and ICT display and functionalities. The latter includes case finding and selection of the target population, pathway definition and quality improvement process. CONCLUSIONS: The Feasibility Framework provides a list of key elements that should be considered for an effective implementation of population risk stratification interventions. It helps to identify, plan and consider relevant elements to ensure a proper RS implementation.

Siglec-1-positive plasmacytoid dendritic cells (pDCs) in human peripheral blood: A semi-mature and myeloid-like subset imbalanced during protective and autoimmune responses.

Plasmacytoid dendritic cells (pDCs) play a central role in the pathogenesis of systemic lupus erythematosus (SLE) as IFN-α producers and promoters of T-cell activation or tolerance. Here, we demonstrated by flow-cytometry and confocal microscopy that Siglec-1, a molecule involved in the regulation of adaptive immunoresponses, is expressed in a subset of semi-mature, myeloid-like pDCs in human blood. These pDCs express lower BDCA-2 and CD123 and higher HLA-DR and CD11c than Siglec-1-negative pDCs and do not produce IFN-α via TLR7/TLR9 engagement. In vitro, Siglec-1 expression was induced in Siglec-1-negative pDCs by influenza virus. Proportions of Siglec-1-positive/Siglec-1-negative pDCs were higher in SLE than in healthy controls and correlated with disease activity. Healthy donors immunized with yellow fever vaccine YFV-17D displayed different kinetics of the two pDC subsets during protective immune response. PDCs can be subdivided into two subsets according to Siglec-1 expression. These subsets may play specific roles in (auto)immune responses.

Statistical approach for optimization of external quality assurance (EQA) studies of molecular and serological viral diagnostics.

Management of viral diagnostic quality is based on external quality assurance (EQA), where laboratories involved in diagnostics of a targeted virus are offered to analyze a panel of blinded samples. The utility of EQAs is compromised because of the absence of an approach to EQA design which upfront defines acceptance criteria and associated statistical analysis ensuring fair and consistent interpretation. We offer a rigorous statistically based approach for EQA planning. Instead of a conventional performance characteristic (the score) which is calculated as the sum of the points for correctly identified samples in a blinded test panel, Youden index is used as the performance measure. Unlike the score, Youden index requires an estimate of sensitivity and specificity and incorporates the relationship of these performance parameters. Based on the assumption that the coordinator is a reputable expert of viral diagnostics, the performance of the coordinator's laboratory is defined as a proficiency standard for performance evaluation. The immediate goal of EQA is defined as to obtain a statistically reliable estimation for every laboratory whether its performance meets the proficiency standard, while the overall goal is to match every laboratory to its specific performance level. Dependence of informational capacities of test panel from the panel size and content is quantitatively analyzed and the optimal design and informational capacities of both idealized panels (whose size is not restricted by financial factors) and currently feasible panels are considered. Our approach provides the basis both for rational design of currently feasible EQA test panels and for an increased panel size.

International external quality control assessment for the serological diagnosis of dengue infections.

BACKGROUND: Dengue is endemic to the tropics and subtropics, and the most frequent of arthropod-borne viral diseases. Reliable diagnosis of dengue infection is important not only in clinical care but also in disease surveillance, the control of outbreaks, and the development of new vaccines. The diagnosis of dengue infection is usually established by a variety of commercial or in-house serological protocols. The European Network for the Diagnostics of Imported Viral Diseases (ENIVD) recognized the need to survey the accuracy of dengue serological diagnostics in current use, and organized an external quality assurance (EQA) study of dengue serological practice in diagnostic laboratories. METHODS: A 15-sample panel, consisting of sera reactive against dengue plus specificity and negative controls, was sent to 48 laboratories for serological testing. The results returned by the participating laboratories were anonymized, scored, and subjected to comparison and statistical analysis. RESULTS: Ten laboratories rated all samples correctly with regard to IgM, and only three achieved the full score for IgG detection. The main handicaps in assay performance were suboptimal sensitivity of in-house IgM detection protocols by comparison with better-performing commercial ELISA tests, and the presence of IgG cross-reactivity with heterologous flaviviruses. Differences of detail in the methodology of dengue IgG antibody detection appear to underlie the disparities in accuracy observed between laboratories. CONCLUSION: This EQA study demonstrates that there is room for many laboratories to improve sensitivity in the detection of anti-dengue virus IgM antibodies, against the benchmark set by commercial antibody capture ELISA tests. The EQA shows also that cross-reactivity is a continuing issue, and IgG detection protocols must be optimized to increase their specificity.

West Nile Virus Emergence in Germany 2019: Looking for Hidden Human West Nile Virus Infections.

Background: Autochthonous human West Nile virus (WNV) infections were notified in the infectious disease surveillance system in Germany in 2018 for the first time and every year since then. Since clinically apparent infections are infrequent, we conducted two studies to investigate subclinical infections of this emerging disease in Germany in 2019 to detect infections not visible to surveillance based on symptomatic infections: limited-scope blood donor testing and a serosurvey among employees at two Berlin zoos with a history of demonstrated WNV infections in animals. Methods: For the zoo study, employees of the two zoos in Berlin were invited to participate in the study in late 2019. Blood samples were drawn and tested for the presence of antibodies (immunoglobulin M [IgM] and immunoglobulin G [IgG]) against WNV, and two other flaviviruses present in Germany: Usutu virus and Tick-borne encephalitis virus (TBEV). For the study in blood donors, four blood establishments with collection sites in regions with documented WNV-infected animals in 2018 and 2019 participated in the study. All donations in these regions were tested for WNV genome from July to November 2019. Results: In the enzyme-linked immunosorbent assay, none of the 70 tested zoo employees were WNV IgM-positive, 8 were WNV IgG-positive, additional 2 participants had equivocal results. All 10 were negative in the virus neutralization test (VNT) for WNV, but positive in the VNT for TBEV. None of the 4273 samples from blood donors tested in areas with WNV-infected animals was positive for WNV-RNA. Conclusion: Our results indicate that WNV circulation in Germany, though clearly documented in animals in 2019, apparently affected very few humans. Still areas with WNV-positive animals remain risk areas for human infection as well.

Profiles of Dementia Caregivers according to Psychosocial and Resource Variables. Importance of Kinship.

The present study aims to analyze the existence of different profiles in family caregivers of people with dementia according to psychosocial and resource variables. In addition, it aims to study whether there is a greater representation of each kinship group in each of the profiles and if there are differences in emotional distress among such profiles considering the kinship with the care-recipient. Participants were 288 family dementia caregivers, divided into four kinship groups (wives, husbands, sons and daughters). Psychosocial (familism, dysfunctional thoughts and experiential avoidance), resource (leisure activities and social support) and outcomes (depressive, anxious and guilt symptomatology) variables were collected. A hierarchical cluster analysis using Ward's method, an exploratory factor analysis of two fixed factors and contingency tables were performed. Five clusters were obtained: Low psychosocial vulnerability-High resources, Low psychosocial vulnerability-Low resources, Mixed, High psychosocial vulnerability-High resources, and High psychosocial vulnerability-Low resources. Results suggested that clusters associated with lower distress were the Low psychosocial vulnerability-High resources and the High psychosocial vulnerability-High resources. Clusters associated with higher distress were the Low psychosocial vulnerability-Low resources and Mixed. High levels of dysfunctional thoughts, familism and experiential avoidance do not always have a maladaptive function. This could depend on sociocultural and resource variables such as the kinship with the caregiver or perceived social support. The identification of profiles of family caregivers potentially needing protection and vulnerable to psychological distress could help to increase the effectiveness of interventions aimed at this population.

Longitudinal effects of ambivalent and guilt feelings on dementia family caregivers' depressive symptoms.

BACKGROUND: The world prevalence of people with dementia is increasing. Most of the care received by people with dementia is provided by family caregivers, and this prolonged activity has a significant impact on caregivers' levels of depression. Stressors and frequency of leisure are known predictors of caregivers' depressive levels. The longitudinal impact of caregivers' ambivalent and guilt feelings is unknown. METHODS: Participants were 177 family caregivers of relatives with dementia who were assessed three times during a 2-year period. In addition to demographic variables, psychological symptoms of the dementias, and frequency of leisure activities, caregivers' ambivalent feelings, guilt, and depressive symptoms were measured. The longitudinal association of changes in these variables with changes in caregivers' depressive symptoms over time was assessed using mixed linear models. RESULTS: Changes over time in the assessed variables predicted 48.05% of variance of changes over time in depressive symptoms. Even when variables strongly associated with increased depressive symptoms were controlled (lower caregivers' age and educational level, higher reaction to BPSD, and lower leisure activities), increases in ambivalence and guilt contributed to an increase of 9.22% of the variance of changes depressive symptoms over a 2-year period. The effects of ambivalent feelings on depression are indirect, mediated by guilt feelings. Cessation of caregiving do not seem to alter these findings. CONCLUSIONS: Caregivers' ambivalent and guilt feelings are significant predictors of caregivers' mental health. Caregivers may significantly benefit from early detection of ambivalent and guilt feelings and preventive strategies targeting triggers associated with ambivalent and guilt symptoms.