Suicide Severity Research Articles

Cluster analysis of suicidal ideation and influencing factors among Spanish teachers

Suicidal ideation signals a higher suicide risk, particularly among teachers, affecting their well-being and impacting student development and academic success. This study, the first to use standardized measures with Spanish teachers, examines suicidal ideation among 1,251 educators from 107 schools. It analyzes suicidal thoughts and their associated risk and protective factors using a cross-sectional design. Results show an 18.86% prevalence of suicidal ideation, with 12.39% occurring in females. Anxiety and depression may act as risk factors, while emotional intelligence and resilience might serve as protective factors in identifying teachers with and without suicidal thoughts. The analyses identified four clusters based on suicidal ideation severity and psychological traits, indicating a need for enhanced targeted interventions. Main limitations include the cross-sectional design, reliance on self-reported data, and the lack of a broader perspective on sociocultural variables. Evidence highlights the need for tailored interventions to reduce teachers’ suicidal thoughts and improve their well-being.

Symptom profile in suicide attempters during the COVID-19 pandemic: Relationships with suicide outcomes.

Suicidal behavior constitutes a multi-cause phenomenon that may also be present in people without a mental disorder. This study aims to analyze suicidal behavior outcomes in a sample of attempters, from a symptom-based approach. The sample comprised 673 patients (72% female; M=40.9years) who attended a hospital emergency department due to a suicide attempt. A wide range of clinical factors (e.g., psychopathology symptoms, psychiatric diagnoses, impulsivity, acquired capability), was administered within 15days after the index attempt. Nine psychopathology domains were explored to identify the profile of symptoms, using latent profile analysis. The relationship between the profile membership and suicide outcome (i.e., intensity of suicidal ideation, number of suicide behaviors, and medical injury derived from index attempt) was also studied, using linear and logistic regression. Three psychopathology profiles were identified: high-symptom profile (45.02% of participants), moderate-symptom profile (42.50%), and low-symptom profile (12.48%). High-symptom profile members were more likely to show higher risk of non-suicidal self-injury, acquired capability for suicide, and more severe suicide behavior and ideation. On the other hand, a more severe physical injury was associated with low-symptom profile membership in comparison to membership from the other profiles (OR<0.45, p<.05). A symptom-based approach may be useful to monitor patients and determine the risk of attempt repetition in the future and potential medical injury, and to optimize prevention and intervention strategies.

Patterns and predictors of help-seeking intentions for suicidal ideation compared to other health conditions among rural Chinese adults

Psychological help-seeking for suicidal ideation is a critical aspect of effective suicide prevention. Past research has documented low help-seeking amongst rural residents in China. This study investigates the patterns and predictors of help-seeking intentions for suicidal ideation versus mental (depression) and physical (heart disease) health conditions among Chinese rural residents using General Help-Seeking Questionnaire Vignette version. A total of 143 rural participants from sixteen villages in Hubei province of China completed the survey via home-visiting interviews. Results revealed a general trend that the help-seeking intentions decreased as the helping sources shifted from close others (spouses, family, etc.) to professional helpers and online sources. Additionally, rural residents with higher educational levels, high self-efficacy, and more severe suicide ideations were more willing to seek help; and suicide literacy was found to be negatively associated with help-seeking intentions. The implications of the research findings are discussed.

MIGRATION RISK OF DEVELOPING PSYCHOSOMATIC DISORDERS IN SOCIALLY PROSPEROUS YOUNG PEOPLE WITH INCREASED NEUROPSYCHIC AND INTELLECTUAL LOAD

RELEVANCE: The relevance of the study is due to the lack of systematic data on the cause-and-effect relationships between the territorial remoteness of the initial and final settlements when changing place of residence with the risk of developing psychosomatic disorders in a person with increased neuropsychic and intellectual stress. AIM: To develop an integrative indicator of the risk of developing psychosomatic disorders in young people when changing their place of residence. MATERIAL AND METHODS: The study involved students of the Volgograd State Medical University, 97 men and 99 women aged 18-22 years. Nonresident respondents accounted for 44% (45 people) of the sample population of men and 60% (61 people) of the sample population of women. The cross-sectional study was carried out in June 2023, during the spring session, 9 months after the start of university studies, and, accordingly, from the moment nonresident students changed their place of residence. The level of systemic maladjustment of respondents was assessed using the I.N. Gurvich test. The indicators of the Giessen Somatic Complaints Questionnaire and indicators of anxiety-depressive disorders (HADS scale) were taken into account, and the presence of suicidal ideation was determined - according to the suicidal ideation module of the Columbia Suicidal Severity Scale (C-SSRS). The distances (km) between the initial and final settlements of the respondents’ place of residence were calculated. RESULTS: A systemic direct statistically significant relationship was identified between the severity of psychosomatic disorders and the distance of migration movement of young people from the place of previous residence to the final point of residence. Four degrees of migration risk have been identified with zero (up to 20 km) and subsequent three (up to 400, up to 800 and over 800 km) territorial ranges of somatization risk. The control critical values of the migration risk indicator for the development of psychosomatic disorders for men and women were calculated, determining that the migration risk of somatization in young people occurs when the territorial distance of the place of residence from the place of previous residence is 400 km or more. CONCLUSION: The connections between the territorial remoteness of the initial and final settlements when changing place of residence, with the risk of developing psychosomatic disorders in a person under conditions of an intense educational process, are characterized.

Suicidal thinking and behavior in young people at Clinical High Risk for Psychosis: Psychopathological considerations and treatment response across a 2-year follow-up study.

Suicidal ideation has high rates among individuals at Clinical High Risk for Psychosis (CHR-P). CHR-P mental states are currently defined as attenuated psychotic symptoms, brief intermittent psychotic symptoms, or genetic risk and functioning deterioration syndrome. However, the relationship between psychotic experiences and suicidality in CHR-P subjects is still not fully understood. Research emphasizes the need to address suicidality in CHR-P individuals due to its incidence and severe socio-economic impact. This study aimed to assess the baseline prevalence and 2-year incidence rates of suicidal thinking and behaviors in an Italian CHR-P sample, investigate the stability of suicidal ideation over 2 years, and examine its associations with treatment outcomes, sociodemographic characteristics, and clinical factors. CHR-P participants were treated in an "Early Intervention in Psychosis" program and completed the PANSS and the GAF scale at baseline and every 12 months. 180 CHR-P individuals were enrolled (92 with suicidal ideation [SI+]). SI+ subjects had a higher baseline prevalence of past suicide attempts. Over 2 years, a decrease in suicidal ideation severity was observed in the total group. Longitudinal improvement in disorganized symptoms was a key predictor of the decrease in suicidal ideation. Participants with a history of suicide attempts were more likely to attempt again. Addressing disorganization is crucial for suicide prevention in the CHR-P population. Continuous risk monitoring and preventive actions are needed for those with past suicide attempts.

Prevalence and clinical correlates of impaired fasting blood glucose in children and adolescents with depressive disorder and relationship with triglyceride and high-density lipoprotein ratio

Depressive disorder is a significant public health problem worldwide, which adversely affects children and adolescents’ health. Impaired fasting blood glucose (IFG) is more common in depressive disorder, which becomes a clinical problem that needs to be focused on. The study purposed to determine the prevalence and related factors of IFG in Chinese children and adolescents with depressive disorder and the relationship between triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) ratio and IFG. This research encompassed 756 individuals aged 8 to 18 with major depressive disorders, all diagnosed under DSM-5 criteria at the Third People’s Hospital of Fuyang from January 2020 to December 2021. We detected fasting blood glucose (FBG) and lipid levels and assessed the suicidal behaviors and depressive symptoms severity of each participant. The sociodemographic and included study variables were collected and analyzed. Our study employed multiple logistic regression to discern independent factors affecting IFG in conjunction with depressive disorders among children and adolescents. The prevalence of IFG was 6.5% (49/756). IFG was positively correlated with FBG, BMI, TG, TG/HDL-C, and was negatively correlated with gender and the type of antidepressant drug taken. Binary logistic analysis showed that male (OR = 2.57, 95% CI: 1.43–4.63, P = 0.002) and higher levels of TG (OR = 1.63, 95% CI: 1.11–2.38, P = 0.013) were independently associated with IFG in children and adolescents with depressive disorder. The incidence of IFG in children and adolescents with depressive disorder was high and was positively related to the TG/HDL-C ratio. The evaluation and management of IFG in pediatric depression should extend beyond pharmacological interventions. Comprehensive strategies in both assessment and management of IFG are essential to address this condition effectively in young patients facing depressive disorders.

Severe suicide attempts, Day of the Week, and Holidays in South Korea: A Nationwide Case Time Series Study

Severe suicide attempts, Day of the Week, and Holidays in South Korea: A Nationwide Case Time Series Study

Brief psychological intervention for suicide prevention based on problem-solving applied in different formats to people over 50 years old: protocol for a randomized controlled trial

BackgroundSuicide is a major public health problem, especially among individuals over 50 years old. Despite the suitability of this life stage for prevention, research on the efficacy of psychological interventions is scarce and methodologically limited, affecting their clinical utility and efficacy. Brief, flexible interventions that can be applied both in-person and remotely are needed. This study aims to evaluate the efficacy of a brief problem-solving-based suicide prevention program applied through various modalities to individuals over 50 years old.MethodsA randomized controlled trial will be conducted. A sample of 212 adults aged 50 or older with suicidal ideation will be randomly assigned to a problem-solving-based psychological intervention administered face-to-face (PSPI-P; n = 53), by telephone multiconference (PSPI-M; n = 53), via a smartphone app (PSPI-A; n = 53), or to a usual care control group (UCCG; n = 53). The intervention will be delivered in 7 sessions or modules of 90 min each. Blind trained evaluators will conduct assessments at pre-intervention, post-intervention, and follow-ups at 3, 6, and 12 months. The primary outcome will be suicidal ideation evaluated using the Suicidal Ideation Scale (SSI) and the Columbia Suicide Severity Rating Scale (C-SSRS). Secondary outcomes will include hopelessness, anxiety and depression symptoms, reasons for living, impulsivity, problem-solving skills, social support, anger syndrome, gratitude, personality, dropouts, treatment adherence, and satisfaction with the intervention.DiscussionThis study will provide evidence of the efficacy of a brief problem-solving-based intervention for suicide prevention in individuals over 50 years old, administered face-to-face, by telephone multiconference, and via a smartphone app. If results are favorable, it will indicate that an effective, accessible, clinically and socially useful suicide prevention intervention has been developed for affected individuals, families, and communities.Trial registrationClinicalTrials.gov NCT06338904. Registered April 1, 2024.

Measuring psychache as a suicide risk variable: A Mokken analysis of the Holden's Psychache Scale

BackgroundThe Psychache Scale (PAS) is a questionnaire measuring trait-level psychological pain with satisfactory internal consistency and a strong correlation with suicidal ideation severity. However, inconsistent results have been reported for the PAS dimensionality. In the present study we used a non-parametric item response theory model, called Mokken Scale Analysis (MSA), to refine an unidimensional version of the PAS. MethodsThe sample was composed of 400 Italian adults (312 females and 88 males) nonrandomly recruited from the general population. ResultsA final set of 10 items satisfied the unidimensionality, local independence, and monotonicity assumptions, although it did not satisfy the double monotonicity assumption. The internal consistency of the PAS-10 was satisfactory (ordinal alpha = 0.98, ω = 0.97, and AVE = 0.82), and ROC curves analysis indicated good discriminant validity when differentiating participants with higher suicide risk from those with lower suicide risk. LimitationsStructural invariance between nonclinical and clinical samples was not investigated, and the presence of suicide ideation and behaviors was assessed with self-report measures with potential under-reporting of the phenomenon. ConclusionThe PAS-10 resulted to be a potentially valid and unidimensional measure of psychological pain (i.e., psychache) that could be used to screen adults at higher risk for suicide. Future studies are needed to investigate psychometric properties of the PAS-10 in clinical samples and to replicate results in independent samples.

Means to an end: Characteristics and follow-up of emergency department patients with a history of suicide attempt via medication overdose.

Availability and accessibility of a wide range of medications may be a contributing factor to rising medication-related overdose (OD) rates. Treatment for both suicide attempts (SAs) and ODs often occurs in the emergency department (ED), highlighting its potential as a screening and intervention point. The current study aimed to identify sociodemographic and clinical characteristics of individuals who reported SA via medication OD compared to other methods and to examine how these patients' suicide severity and behaviors differed over 12-month post-ED follow-up. Data were analyzed from Phases 1 and 2 of the Emergency Department Safety Assessment and Follow-up Evaluation multicenter study (N = 1376). Participants with a history of SA (n = 987) were categorized based on whether they indicated a past medication-related SA via OD. Of participants with history of SA, 62.7% (n = 619) reported medication OD for either their most serious or their most recent SA. Multivariate analyses indicated female birth sex, diagnosis of bipolar disorder, and having some college education were significantly associated with membership in the medication OD attempt group (p <0.05). Of those who attempted suicide over the 12-month follow-up, nearly 60% of participants in the medication OD attempt group reported a subsequent SA via OD over follow-up. However, nearly half (46.5%) of participants with no medication OD at baseline also reported medication OD at follow-up. Among patients presenting to the ED, females, individuals with bipolar disorder, and patients with a college education, respectively, may be at highest risk for SAs via medication OD. Prospectively, medication OD appears to be a frequent method, even among individuals with no prior attempt via OD, as demonstrated by the high percentage of patients who did not have a medication OD at baseline, but reported a medication OD during follow-up.

Initial evaluation of a personalized advantage index to determine which individuals may benefit from mindfulness-based cognitive therapy for suicide prevention

ObjectiveDevelop and evaluate a treatment matching algorithm to predict differential treatment response to Mindfulness-Based Cognitive Therapy for suicide prevention (MBCT-S) versus enhanced treatment-as-usual (eTAU). MethodsAnalyses used data from Veterans at high-risk for suicide assigned to either MBCT-S (n = 71) or eTAU (n = 69) in a randomized clinical trial. Potential predictors (n = 55) included available demographic, clinical, and neurocognitive variables. Random forest models were used to predict risk of suicidal event (suicidal behaviors, or ideation resulting in hospitalization or emergency department visit) within 12 months following randomization, characterize the prediction, and develop a Personalized Advantage Index (PAI). ResultsA slightly better prediction model emerged for MBCT-S (AUC = 0.70) than eTAU (AUC = 0.63). Important outcome predictors for participants in the MBCT-S arm included PTSD diagnosis, decisional efficiency on a neurocognitive task (Go/No-Go), prior-year mental health residential treatment, and non-suicidal self-injury. Significant predictors for participants in the eTAU arm included past-year acute psychiatric hospitalizations, past-year outpatient psychotherapy visits, past-year suicidal ideation severity, and attentional control (indexed by Stroop task). A moderation analysis showed that fewer suicidal events occurred among those randomized to their PAI-indicated optimal treatment. ConclusionsPAI-guided treatment assignment may enhance suicide prevention outcomes. However, prior to real-world application, additional research is required to improve model accuracy and evaluate model generalization.

Distinct Effects of Major Affective Disorder Diagnoses and Suicidal Symptom Severity on Inhibitory Control Function and Proinflammatory Cytokines: Single-Site Analysis of 800 Adolescents and Adults.

Inhibitory control function and proinflammatory cytokines play a role in the pathomechanisms underlying major affective disorders and suicidal behavior. However, the distinct or interactive effects of major affective disorders and suicidal symptom severity on inhibitory control function and proinflammatory cytokines remain unclear. This study included 287 patients with bipolar disorder, 344 with major depressive disorder, and 169 healthy controls. We categorized the participants into 3 groups based on Montgomery-Åsberg Depression Rating Scale (MADRS) item 10 (suicidal symptoms) score: 0, 2 or 3, and ≥4. The participants completed the go/no-go task and the measurements for C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) levels. Errors in the go/no-go task were associated with suicidality (P = .040), regardless of the severity of suicidal symptoms and diagnosis. An elevated CRP level was especially associated with a Montgomery-Åsberg Depression Rating Scale item 10 score ≥4 (P = .001). An increased TNF-α level could distinguish bipolar disorder from major depressive disorder (P < .001). Our study indicated the distinct effects of major affective disorder diagnosis and suicide symptom severity on inhibitory control function and CRP and TNF-α levels. Importantly, individuals with the poorest inhibitory control function and highest CRP levels had more severe suicidal symptoms.

Classification of suicidal ideation severity from Twitter messages using machine learning

Depression has become a major mental health problem in Thailand and can lead to suicidal ideation. As suicidal ideation may vary in intensity and lead to suicide attempts, early detection of suicidal ideation severity should be implemented. This research presents text classification models for the prediction of suicidal ideation severity. A dataset of Twitter messages in Thai was used to develop several classification models. A web application prototype was also developed to predict suicidal ideation severity and introduce self-therapy based on Cognitive Behavioral Therapy to its users for managing negative automatic thoughts. The application prototype received satisfactory feedback during the user experience assessment. The results of this research highlight the importance and need for socio-technical systems to help with early suicidal ideation detection and early therapy in the social environment where mental health support is inadequate.

Clinicians’ perspectives on strategies for suicide prevention in Pakistan: a qualitative inquiry

Suicide is a public health concern and represents one of the increasing causes of mortality worldwide. In Pakistan, the severity of suicide is worsened by the lack of a national prevention program and adequate mental health facilities. This study, through 16 in-depth interviews with clinicians, aimed to identify prevention strategies. Two main categories emerged: community-level strategies (eg raising awareness, psychoeducation, restricting access to lethal means) and clinician-level strategies (eg training programs, safety plans, fundraising, tele-counseling). Effective prevention requires comprehensive policies to overcome existing barriers.

Relations between worry, thought control, suicidal ideation and attempt history

ABSTRACT Background Thought processes such as worries are often described as difficult to control and predict suicidal thoughts and behaviors (STBs). Due to their uncontrollable nature, worries may lead to STBs as people attempt to escape their own internal thought processes. Objective Examine the indirect role of perceived uncontrollability of one’s thoughts in the relationship between worry and STBs. Design and Method We used stepwise mediation models to examine the proposed relationship in a sample of 145 undergraduates with lifetime suicidal ideation. STBs were categorized into (1) severity of lifetime suicidal ideation, (2) likelihood and (3) severity of recent suicidal ideation, and (4) lifetime suicide attempt. The likelihood and severity of recent ideation were separated due to the skewed nature of suicidal thoughts, with many people reporting zero ideation. Results Worry was related to the severity of lifetime ideation, the likelihood of reporting recent ideation, and the severity of recent ideation through lower levels of perceived ability to control one’s thoughts. Worry was not related to a lifetime suicide attempt. Conclusion The perception that one’s thoughts are uncontrollable may be a core feature of worry for the development and worsening of suicidal thinking. Interventions targeting internal perceptions of uncontrollability may be beneficial for suicidal ideation management.

Development and Validation of Electronic Health Record Measures of Safety Planning Practices as Part of Zero Suicide Implementation.

Safety planning for suicide prevention is an important quality metric for Zero Suicide implementation. We describe the development, validation, and application of electronic health record (EHR) programs to measure uptake of safety planning practices across six integrated healthcare systems as part of a Zero Suicide evaluation study. Safety planning was documented in narrative notes and structured EHR templates using the Stanley Brown Safety Planning Intervention (SBSPI) in response to a high-risk cutoff score on the Columbia Suicide Severity Rating Scale (CSSRS). Natural Language Processing (NLP) metrics were developed and validated using chart review to characterize practices documented in narrative notes. We applied NLP to measure frequency of documentation in the narrative text and standard programming methods to examine structured SBSPI templates from 2010-2022. Chart reviews found three safety planning practices documented in narrative notes that were delivered to at least half of patients at risk: professional contacts, lethal means counseling for firearms, and lethal means counseling for medication access/storage. NLP methods were developed to identify these practices in clinical text with high levels of accuracy (Sensitivity, Specificity, & PPV ≥ 82%). Among visits with a high-risk CSSRS, 40% (Range 2-73% by health system) had an SBSPI template within 1 year of implementation. This is one of the first reports describing development of measures that leverage electronic health records to track use of suicide prevention safety plans. There are opportunities to use the methods developed here in future evaluations of safety planning.

Digital phenotypes of real-time suicidal ideation: Correlates and consequences.

Suicidal ideation variability refers to within-day fluctuations in suicidal ideation, and has recently been proposed as an indicator of suicide risk. However, not much is known yet about its correlates and clinical relevance. We examined characteristics of real-time suicidal ideation using Ecological Momentary Assessment in 82 individuals with current active suicidal ideation. Data were collected four times daily over 21 days. Latent profile analysis was used to identify subtypes of suicidal ideation. We further examined sociodemographic and clinical correlates of the profiles, and their association with the occurrence of suicide attempts during a 1-year follow-up. We identified three "digital" phenotypes of suicidal ideation that differed on the frequency, intensity and variability of ideation. The profiles were: high frequency, high intensity, moderate variability (Phenotype 1), moderate/high frequency, moderate intensity, high variability (Phenotype 2), and moderate frequency, low intensity, low variability (Phenotype 3). Phenotypes 1 and 2 were associated with a worse clinical profile at baseline (higher suicidal ideation and depressive symptom severity), and increased odds of suicide attempt during follow-up, compared to Phenotype 3. Phenotype 1 was further characterized by repeated suicidal behavior. Two phenotypes of real-time suicidal ideation were identified that appear to confer a higher risk of suicidal behavior in the near future (12 months). These phenotypes were characterized by higher variability of suicidal ideation-and also higher intensity and frequency of ideation. Considering the small sample size, the clinical usefulness of the profiles remains to be demonstrated.

Drought and Despair: Investigating the Link Between Severe Weather Events and Suicide Mortality in the U.S.

Drought and Despair: Investigating the Link Between Severe Weather Events and Suicide Mortality in the U.S.

The Mediating Role of Insomnia Severity in the Relationship Between Anxiety Symptoms and Suicidal Ideation: A Real-World Study in a Psychiatric Inpatient Setting.

Insomnia and anxiety symptoms are independent clinical variables involved in suicidal ideation in psychiatric inpatients. In this article, we investigated the relationship among insomnia severity, severity of anxiety symptoms, and suicidal ideation in a sample of psychiatric inpatients with severe mental disorders. We used a mediation model considering insomnia severity as the possible mediator of the relationship between anxiety severity and suicidal ideation. We administered the Columbia Suicide Severity Rating Scale, the Insomnia Severity Index, and the Hamilton Anxiety Rating Scale to 116 consecutive inpatients to the psychiatric unit of Sant'Andrea Hospital in Rome. The effect of anxiety symptoms was mediated by insomnia severity; patients who perceive higher anxiety symptoms were more likely to experience higher levels of insomnia and, thus, higher suicidal ideation intensity. Results showed the importance of assessing and treating both insomnia and anxiety in clinical practice.

Safety Profile of a Cognitively Unimpaired Older Population with Elevated Cerebral Amyloid in a 4.5-Year Clinical Trial

BackgroundPreclinical Alzheimer’s disease is increasingly studied in clinical trials. Although safety signals are routinely monitored in clinical trial populations with Alzheimer’s disease, it can be challenging to identify new safety signals against background rates of age-related medical comorbidities.ObjectivesTo report detailed safety data from a cognitively unimpaired older population with evidence of elevated cerebral amyloid levels on amyloid positron emission tomography in the placebo arm of a Phase 3 clinical trial.DesignPhase 3, 4.5-year, multicenter, placebo-controlled trial.SettingPlacebo data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study.ParticipantsEnrolled participants were aged 65–85 years with a global Clinical Dementia Rating score of 0, a Mini-Mental State Examination score of 2–-30, a Wechsler Memory Scale Logical Memory IIa (delayed recall) score of 6–18, and elevated brain amyloid levels on 18F-florbetapir positron emission tomography.MeasurementsStudy participants who received placebo were followed up with post-baseline safety measures. Assessments included review of concomitant medication and adverse events, the Columbia Suicide Severity Rating Scale, electrocardiograms, and neuroimaging (brain magnetic resonance imaging).ResultsIn total, 591 study participants (mean age [standard deviation] 71.9 [5.0] years) were assigned to and received placebo in the A4 study, and were followed up to 240 weeks. Participants were primarily White (93.9%) and from the United States (86.8%); 60.4% were women. The most common serious adverse events (incidence rate per 100 person-years) were pneumonia (incidence rate=0.4; 95% confidence interval=0.2–0.7) and atrial fibrillation (incidence rate=0.4; 95% confidence interval=0.2–0.7). The most common treatment-emergent adverse events were upper respiratory tract infection (incidence rate=10.9; 95% confidence interval=9.4–12.5), fall (incidence rate=7.7; 95% confidence interval=6.6–9.0), and nasopharyngitis (incidence rate=5.8; 95% confidence interval=4.8–6.9). The most common ischemia-related findings on magnetic resonance imaging were subcortical infarction (incidence rate=1.4; 95% confidence interval=1.0–2.0) and acute ischemia (incidence rate=0.6; 95% confidence interval=0.3–1.0). Emergent amyloid-related imaging abnormalities with hemosiderin deposition occurred in 32.8% of participants who received placebo; the primary factor associated with these events during the post-baseline period was the number of microhemorrhages at baseline (odds ratio=349.9; 95% confidence interval=247.6–494.4; adjusted p<0.001).ConclusionSafety findings in the placebo-treated group from the A4 study provide a robust characterization of expected safety in a clinical trial population with preclinical Alzheimer’s disease. These results may provide context in planning future studies and safety evaluations during ongoing blinded studies in preclinical Alzheimer’s disease.