Problem Behavior of Dementia Patients Predicts Low-Grade Hypercoagulability in Spousal Caregivers

Background. Low-grade hypercoagulability might be one pathway to explain how the chronic stress of dementia caregiving increases cardiovascular disease risk, but the specific aspects of caregiver stress that elicit hypercoagulability are elusive. We hypothesized that dementia patients' problem behaviors and negative reactions of caregivers to these behaviors would relate to hypercoagulability in caregivers. Methods. One hundred and eight participants (mean age 74 ± 8 years, 70% women) providing in-home care for their spouse with Alzheimer's disease were examined. Caregivers were interviewed about the number of 24 predefined patient problem behaviors in the previous week (range 0-24) and how upset or bothered they felt in response to these behaviors (total score 0-96). Von Willebrand factor, plasminogen activator inhibitor-1, and D-dimer were determined in plasma and standardized z-scores of their concentrations summed into a procoagulant index. Results. Greater number of problem behaviors (ΔR2 = 0.046, p = .014) and negative reactions of caregivers to these behaviors (ΔR2 = 0.044, p = .017) were associated with greater procoagulant index after controlling for sociodemographic factors, major cardiovascular risk factors, health habits, and health problems. However, the number of and reaction to problem behaviors did not significantly predict procoagulant activity independent from each other. Post hoc analysis revealed a positive association between the number of problem behaviors and D-dimer (p = .010, ΔR2 = 0.053), even when controlling for negative reactions (p = .033, ΔR2 = 0.036). Caregiver reaction to problem behaviors was not significantly associated with any procoagulant factor individually. Conclusion. Alzheimer patients' problem behavior and their negative appraisal by the caregiver may contribute to the chronic low-grade hypercoagulable state in dementia caregiver

Association between hospice care and psychological outcomes in Alzheimer's spousal caregivers.

CONTEXT Dementia care giving can lead to increased stress, physical and psychosocial morbidity, and mortality. Anecdotal evidence suggests that hospice care provided to people with dementia and their caregivers may buffer caregivers from some of the adverse outcomes associated with family caregiving in Alzheimer's Disease (AD). OBJECTIVES This pilot study examined psychological and physical outcomes among 32 spousal caregivers of patients with AD. It was hypothesized that caregivers who utilized hospice services would demonstrate better outcomes after the death of their spouse than caregivers who did not utilize hospice. METHODS The charts of all spousal caregivers enrolled in a larger longitudinal study from 2001 to 2006 (N=120) were reviewed, and participants whose spouse had died were identified. Of these, those who received hospice care (n=10) were compared to those who did not (n=22) for various physiological and psychological measures of stress, both before and after the death of the care recipient. An Analysis of Covariance (ANCOVA), with postdeath scores as the dependent variable and pre-death scores as covariates, was used for all variables. RESULTS Significant group differences were found in postdeath depressive symptoms (HAM-D; F(1,29)=6.10, p0.5 between groups. CONCLUSIONS These data suggest that hospice enrollment may ameliorate the detrimental psychological effects in caregivers who have lost a spouse with Alzheimer's Disease. Based on these pilot data, further prospective investigation is warranted

Integration of the Pleasant Events and Activity Restriction Models: Development and Validation of a “PEAR” Model of Negative Outcomes in Alzheimer's Caregivers

This study examined an activity restriction/pleasurable activities mismatch model for psychosocial and health-related outcomes. A total of 108 spousal caregivers of patients with Alzheimer's Disease (AD) were assessed for their experience of social and recreational activities over the past month as well as their perception of how restricted they were for engaging in social and recreational activities. Participants were divided into three groups based on their reported activities and activity restriction: HPLR=High Pleasant Events+Low Activity Restriction (i.e., reference group; N=28); HPHR/LPLR=Either High Pleasant Events+High Activity Restriction or Low Pleasant Events+Low Activity Restriction (N=43); LPHR=Low Pleasant Events+High Activity Restriction (N=37). We hypothesized that participants reporting low pleasant events combined with high activity restriction (LPHR) would demonstrate greater disturbance relative to other two groups in multiple outcome domains, including: (a) greater mood disturbance, (b) greater use of negative coping factors, (c) reduced use of positive coping strategies, (d) reduced report of psychological resource factors (e.g., personal mastery, self-efficacy), and (e) increased report of subjective health difficulties (e.g., sleep disturbance). Results generally supported our hypotheses, suggesting that assessment of both constructs is important for best predicting quality of well-being in AD caregivers, and potentially for establishing maximal effect in behavior therapy for caregivers

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values &lt;5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.</p

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values \u3c5×10 CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Characteristics Associated with Psychological, Physical, Sexual Abuse, Caregiver Neglect and Financial Exploitation in U.S. Chinese Older Adults: Findings from the Population-Based Cohort Study in the Greater Chicago Area

This study examined the socio-demographic and health related characteristics of elder mistreatment (EM) in a community-dwelling older Chinese population. Methods: Guided by a community-based participatory research approach, the PINE study conducted in-person interviews with 3,159 U.S. Chinese older adults aged 60 years and older in the Greater Chicago area from 2011–2013. Participants answered questions regarding psychological, physical and sexual mistreatment, caregiver neglect, and financial exploitation. Definitional approaches for EM subtypes were constructed from least restrictive to most restrictive. Results: The sociodemographic and health-related characteristics associated with EM differed by type of mistreatment and by the operational definition used. Living with fewer people, having been born in countries other than China, poorer health status, and lower quality of life were significantly correlated with physical mistreatment. Only higher education was positively and significantly associated with sexual mistreatment and only poorer health status was consistently correlated with psychological mistreatment among all definitions. Male gender, higher educational levels, higher income, fewer children, and having been in the U.S. for fewer years were significantly correlated with financial exploitation. As for caregiver neglect, older age, having more children, having been in the U.S. for more years, poorer health status, lower quality of life, and worsening health over the past year were consistently correlated with caregiver neglect with different definitions. Conclusions: Prevention and intervention programs on EM should be geared towards specific types of mistreatment. Studies on EM should conduct a thorough analysis to justify the operational definition used