Clinical Research Directory

Future School of Comprehensive Well-Being

Good physical, mental and social health, particularly in childhood and early adolescence, are powerful predictors of positive life trajectories. Contrary to this, problems in these domains expose individuals to negative developmental trajectories. Schools are ideal settings to address these issues due to their incisiveness and long-term impact. However, school-based well-being interventions are not designed to be ingrained in basic pedagogical processes of school, this is, learning, teaching and studying. In this study the effects of a school-based pedagogically ingrained comprehensive well-being trial will be studied, involving curriculum embedded socio-pedagogical activities, designed to cultivate simultaneously learning and their mental, social and physical well-being. In the Future School of Comprehensive Well-Being (SchoolWell) Comprehensive wellbeing pedagogy intervention for primary and lower secondary school students: rationale and study protocol for the SchoolWell cluster randomized controlled trial -study the investigators use a cluster randomized hybrid type 1 effectiveness-implementation design. SchoolWell involves 10 Finnish speaking Teacher Training Schools including both primary and secondary schools. Randomization occurs at the school level. The intervention is a multicomponent implementation strategy that has been co-designed by SchoolWell research team and case schools' teachers. All 5th and 8th graders (aged 11-12 years and 14-15 years), from the control and intervention schools are eligible for the study. Total of 1440 students (560 5th and 880 8th graders) will be recruited for the study (n=717 students from intervention schools and n=723 students from control schools). Data is collected from Grade 5 and 8 students representing schools randomized to experimental (n=5) and control condition (n=5). The control group in Year 1 remains on the waitlist until the start of Year 2, when the second cohort of the experiment (low support condition) for these schools begins. The purpose of the low support condition is to examine whether intervention effects can be achieved with less support than in the high support condition, where researchers are more actively involved. Schools allocated to the intervention group deliver weekly SchoolWell activities over the full school year as part of the regular curriculum. The activities include socio-pedagogical activities, these are modes of teaching, learning and studying, promoting student mental, social and physical well-being as well as learning aligned with regular curriculum goals. Intervention schools have access to six implementation support strategies in addition to the training received as usual delivery to build knowledge and skills. Implementation and effectiveness outcomes are assessed using weekly online surveys, interviews at baseline T0 (8/2024), T1 (11/2024), T2 (4/2025) and at 19-month follow-up (T3; 4/2026) and four dialogues with teachers. Semi-structured interviews with teachers and support staff will be used to examine which implementation strategies worked for whom and under what conditions. The primary outcome is study engagement. Secondary outcomes include measures on learning, mental, social and physical well-being. Economic and process evaluations will also be conducted to determine cost-effectiveness, program acceptability, implementation, adaptability, and sustainability in schools. SchoolWell draws on the Consolidated Standards of Reporting Trials (CONSORT) and the Standards for Reporting Implementation Studies (StaRI) in evaluating the SchoolWell intervention. Also, the Consolidated Framework for Implementation Research (CFIR) is used to guide support strategies. The CFIR provides constructs that have been associated with effective implementation (intervention, outer settings, inner settings, individuals, implementation process). Subsequently, the Proctor's framework is followed to evaluate the implementation process. The framework stands for acceptability (treatment is agreeable or satisfactory), adoption (intention to employ an innovation or evidence-based practice), appropriateness (fit of the innovation to address a particular issue or problem), cost (cost impact of an implementation effort), feasibility (extent to which a new treatment can be successfully carried out in given setting), fidelity (extent how intervention is delivered as intended), penetration (number of providers who deliver treatment), and sustainability (extent to which a newly implemented treatment is maintained). Hypotheses are: H1. SchoolWell 1 intervention will have a positive effect on student-level outcomes (8- and 19-month post-tests). H2. The multidisciplinary intervention enhances both learning and mental, physical, and social well-being.

PREWELL Digital Well-being Promotion Intervention With the BitHabit App

Mental wellbeing is a major public health concern, and digital interventions have emerged as a scalable approach for promoting mental well-being and healthy lifestyle behaviors. However, evidence regarding long-term effectiveness and the role of user engagement remains limited. This study evaluates the effectiveness of the BitHabit digital wellbeing application in promoting mental wellbeing and healthy lifestyle among adults living in North Savo, Finland. The BitHabit application is a digital behavior change intervention designed to support mental wellbeing through the adoption of small, self-selected wellbeing-promoting habits. The application incorporates principles of self-determination theory, habit formation, self-monitoring, and behavior change techniques. Participants select habits from a library of well-being-promoting activities and track their implementation over time. The intervention study uses a stepped-wedge randomized controlled design in which all participants eventually receive access to the intervention, while participants awaiting access serve as controls. Adults aged 18 to 64 years living in North Savo were recruited between 2024 and 2025 through population registry sampling and open public recruitment. Following informed consent and baseline assessment, participants were randomly allocated to receive access to the intervention at different time points during the study. Power calculations using Monte Carlo simulations indicated that approximately 1,600 participants would provide 80% power to detect a standardized mean difference of 0.30 in mental wellbeing (SWEMWBS), assuming four intervention sequences, five measurement occasions, a within-person intraclass correlation coefficient of 0.70, and 30% attrition. The primary outcome mental wellbeing is assessed using the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS). Secondary outcomes include depressive symptoms measured with the Patient Health Questionnaire (PHQ-9), self-reported capabilities, loneliness measured with the UCLA 3-item Loneliness Scale (UCLA-3), life satisfaction measured on a 0-10 scale, and self-reported health behaviours. Outcomes are measured at baseline and repeated follow-up assessments throughout the study. We hypothesize that participants receiving the intervention will show greater improvement in all primary and secondary outcome measures compared with the control condition. App usage data are used to evaluate intervention adoption and engagement and to examine whether effectiveness differs according to actual intervention use. Statistical analyses will be conducted using mixed-effects regression models that account for the stepped-wedge design and repeated measurements within participants. Models will include fixed effects for intervention exposure and time, and a random intercept for participants. Estimates will be reported with 95% confidence intervals and a two-sided significance level of 0.05. In addition to quantitative outcome assessments, participant experiences and acceptability of the intervention will be evaluated with user satisfaction questionnaires and qualitative interviews conducted among a subset of participants. These data will be used to assess perceived usefulness, user experiences, and opportunities for further development of the intervention. In addition to questionnaire and app usage data, participants will be linked to regional and national administrative registers. Register-based follow-up covers the period from one year before study enrolment until up to ten years after study completion. Data sources include health and social care registers, prescription and reimbursement registers, employment-related registers, and population registers. These data will be used to evaluate the long-term effectiveness and cost-effectiveness of the intervention, including health service use, medication use, social outcomes, and associated costs.

Integrated Collaborative Care Teams for Youth With Mental Health and/or Addiction Challenges (YouthCan IMPACT)

Among youth, the prevalence of mental health and addiction (MHA) disorders is roughly 20%, yet youth are challenged to access services in a timely fashion. To address MHA system gaps, this study will test the benefits of an Integrated Collaborative Care Team (ICCT) model for at-risk youth with MHA challenges. In partnership with community agencies, adolescent psychiatry hospital departments, and family health teams, investigators have developed an innovative model of service provision involving rapid access to MHA services. This model will be implemented and compared to the usual treatment youth receive in hospital-based, outpatient, mental health clinics in Toronto. A rapid, systematic, approach to MHA services geared to need in a youth-friendly environment is expected to result in better MHA outcomes for youth. Moreover, the ICCT approach is expected to decrease service wait-times, be more youth- and family-centred, and be more cost-effective.

Group-based Stabilization and Skill Training for Patients With Lasting Posttraumatic Reactions in Mental Health Care

This study evaluates the addition of a group based stabilization and skill-training intervention to individual out-patient treatment for long lasting post-traumatic reactions. Half of the participants will receive the combined treatment while the other half will receive individual treatment as usual.

LLM Psychiatric Intake AI Clinical Performance Study

This study will evaluate the clinical performance and applicability of a large language model-based psychiatric intake support system for caregivers of patients undergoing an initial or re-intake psychiatric evaluation. Caregivers will complete a single adaptive AI interview remotely before the scheduled outpatient visit. The system will generate a structured clinician-facing report and diagnostic screening candidates for nine prespecified target conditions. Treating clinicians will review the AI-generated information while retaining full authority over the final clinical assessment and diagnosis. The system will be evaluated in terms of diagnostic-assistance performance, interview and information-collection performance, documentation quality, acceptability and user experience, and safety.

Group Transdiagnostic Cognitive Behavioural Therapy for Intolerance of Uncertainty Versus Applied Relaxation

Many people find uncertainty distressing, but for some, it may become overwhelming and drive persistent anxiety, worry, and avoidance. This tendency is called intolerance of uncertainty (IU), and appears across many mental health conditions, including generalised anxiety, social anxiety, depression, and obsessive-compulsive disorder, which is why researchers describe it as a transdiagnostic feature. A type of therapy called Cognitive Behavioural Therapy for Intolerance of Uncertainty (CBT-IU) has been shown to reduce anxiety in previous trials. What remains to be known is how uncertainty changes when targeted directly, and whether the same mechanism applies across diagnoses. IU has mostly been measured using questionnaires, which indicate whether people find uncertainty difficult, but not what is actually happening when they encounter it. Recent research suggests that IU is not a single trait but a set of differences in how people estimate different kinds of uncertainty. Therefore, in addition to standard questionnaires, computer-based tasks will be used to explore an "uncertainty fingerprint" for each participant, capturing different aspects of uncertainty processing in a way that self-report measures cannot. In this study, the investigators are comparing CBT-IU, adapted to work across disorders, against Applied Relaxation. Applied relaxation is a well-established therapy that teaches people to notice and release physical tension but does not focus on uncertainty. Adults with high IU and anxiety symptoms (regardless of formal diagnosis) will be randomly allocated to one of the two 12-session group therapies. The investigators will measure anxiety and IU using standard questionnaires as the primary outcomes. Additionally, cognitive tasks will be used to measure the uncertainty fingerprint before therapy, immediately after, and three months later. The aim is to test whether reductions in IU are specific to CBT-IU rather than shared with an equally credible therapy that does not target uncertainty. Going beyond self-reports, the trial will then begin to resolve which specific aspects of uncertainty processing change, so that future treatments can be more precisely targeted and better matched to each person.

Psychosocial Factors in Dual Diagnosis in a General Hospital

Dual diagnosis, defined as the co-occurrence of a mental disorder and a substance use disorder, is frequently associated with increased clinical severity, functional impairment, and poorer health outcomes. Identifying psychosocial protective factors related to better clinical and functional outcomes is essential to improve patient care and treatment planning. The aim of this observational, cross-sectional, single-center study is to analyze psychosocial protective factors and their association with clinical-functional outcomes in hospitalized patients with dual diagnosis. The study will be conducted in a general hospital setting and will include adult inpatients diagnosed with dual diagnosis according to clinical criteria. Sociodemographic, clinical, and psychosocial variables will be collected using standardized assessment tools and clinical records. The results of this study are expected to contribute to a better understanding of psychosocial factors associated with clinical severity and functional outcomes in patients with dual diagnosis, supporting more comprehensive and patient-centered care approaches.

Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression

Background: Major depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD. Objective: To test a study drug (HNK) in people with MDD. Eligibility: People aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254. Design: Participants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity. HNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule: They will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study. They will receive no drugs for 2 to 3 weeks. They will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study. One set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo. ...

Targeted Alternating Current and Cognitive Training Intervention for Cognitive Control in Bipolar Disorders

This study is testing whether a type of gentle brain stimulation, combined with computer-based brain training exercises, can help improve thinking skills in Veterans with bipolar disorder. Veterans with bipolar disorder may have difficulty with skills like stopping to think before acting or adjusting their behavior when things change - problems that can affect daily life and have been linked to a higher risk of serious outcomes. In this study, Veterans with bipolar disorder will complete brain training exercises at home on a computer, paired with a mild electrical brain stimulation called transcranial alternating current stimulation (tACS), delivered through a small headband worn on the forehead. Some participants will receive real stimulation and some will receive an inactive ("sham") version, and neither participants nor most study staff will know which one a person is receiving. All participants will also complete brain wave recordings (EEG), interviews, questionnaires, and various thinking tasks before and after the study to measure any changes. A separate group of Veterans without bipolar disorder will complete the same tests, without any brain stimulation or training, to help researchers understand how much change would happen naturally just from taking the same tests more than once. The goal of this research is to learn whether this combined treatment approach is safe, tolerable, and helpful for improving thinking skills in Veterans with bipolar disorder, and whether Veterans find it an acceptable treatment worth continuing.

A Study of Donanemab (LY3002813) in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ 5)

The reason for this study is to assess the safety and efficacy of donanemab in participants with early Alzheimer's disease. The study duration including screening and follow-up is up to 93 weeks.

Mastering the World of Work (MWW): RCT

The purpose of this study is to conduct a randomized clinical trial for an innovative intervention entitled "Mastering the World of Work" (MWW). MWW aims to improve the employment outcomes of individuals with psychiatric disabilities who experience metacognitive deficits. Metacognitive deficits are represented in diminished capacity to form an integrated sense of self and others and respond to challenges in life. The randomized trial (N=60) will be conducted with recipients of Supported Employment (Individual Placement and Support) services at the Mental Health Center of Greater Manchester, in Manchester, NH. Given COVID-19 safety considerations, the MWW intervention will be delivered in a hybrid manner depending on the preferences of both clinicians and clients at the MHCGM at any given point of the study. The feasibility of remote delivery of the intervention has been established as part of a pilot study conducted at BU CPR. Thus, clinicians may deliver the intervention using HIPAA-complaint ZOOM connection and/or in person. The assessments will be administered at baseline, 6, 12, and 18 months post baseline remotely by BU staff using a HIPAA-complaint ZOOM connection. The RCT will establish preliminary evidence about the incremental effectiveness of the MWW intervention to improve the employment outcomes of individuals with metacognitive deficits who receive high fidelity IPS services. Study participants randomized to the control condition will receive IPS services as usual.

Studying the Health of Asians to Advance Knowledge, Treatments, and Interventions for Depression

SHAKTI (from the Sanskrit word for "power") is a 5-year natural history, longitudinal, prospective study of a cohort of 6,000 participants that will help uncover the socio-demographic, lifestyle, clinical, psychological, and neurobiological factors that contribute to antidepressant treatment response (remission, recurrence, relapse and individual outcomes in depressive disorders) and resilience. As this is an exploratory study, we will assess a comprehensive panel of carefully selected participant specific parameters - socio-demographic (age, sex, gender, race, ethnicity, economic); life habits (physical activity, substance use); clinical (medical history, anxious depression, early life trauma), biological (biomarkers in blood, saliva, urine, stool), behavioral (cognitive, emotional), neurophysiological (EEG), and neuroimaging (magnetic resonance imaging; MRI) with the goal of developing the most robust predictive models of depression treatment response and of outcomes.

AI-Enabled Smartwatch for Medication Adherence in Outpatient Psychiatry

Medication nonadherence remains difficult to measure objectively in psychiatric care. This completed, single-center exploratory randomized trial evaluated whether four weeks of AI-enabled smartwatch medication monitoring improved clinician-rated medication adherence compared with waitlist usual care in psychiatric outpatients aged 12 years or older, predominantly adolescents and young adults with mood disorders.

Measurement of Cardiometabolic Risk in Antipsychotic-Treated Children

The proposed study aims to begin the multi-step process of establishing the reliability and validity of hepatic triglyceride content (HTGC) and carotid artery intima-media thickness (IMT) as biomarkers of cardiometablic risk in children treated for mental illness. The distribution of HTGC and carotid IMT-proximate indicators of cardiometabolic risk-across a range of dual-energy X-ray absorptiometry (DEXA)-measured adiposity in children treated with antipsychotic agents will be characterized in comparison to healthy, untreated, non-psychiatric controls, in order to estimate effect sizes for future studies incorporating these markers. The ability of HTGC and IMT to predict cardiometabolic risk as measured by commonly-used laboratory tests, such as fasting lipids, liver function tests, C-reactive protein and serum fibrinogen, will be assessed.

Tai Chi Effects on Chronic Insomnia in Breast Cancer Survivors: Immune Mechanisms

Breast Cancer is the most common cancer in women. After completion of successful therapy, may behavioral symptoms persist with over 20% of breast cancer survivors reporting chronic insomnia of greater than 6 months duration that fulfils clinical diagnostic criteria with associated functional limitations, decreased quality of life, and possible effects on long-term survival. Behavioral interventions are highly efficacious in the treatment of insomnia and preferred over hypnotic medication when insomnia is chronic. However, insomnia studies conducted in cancer are scarce. The proposed research builds upon program of study that has examined the efficacy of mind-body intervention, Tai Chi Chih (TCC), on health outcomes including sleep impairments. Preliminary studies show that TTC, a slow moving meditation, contributes to improvement in subjective sleep quality, sleep amounts and sleep efficiency. The investigators have further found that sleep, fatigue and proinflammatory cytokine activity are reciprocally related and that TCC decreases the mechanism through TCC carries its effects on sleep outcomes.

Physiological Mechanisms of Therapeutic Horseback Riding Intervention Effects in a Psychiatric Population of ASD Youth

This randomized control trial (RCT) seeks to assess the mechanisms underlying Therapeutic Horseback Riding's (THR) previously observed significant positive effects on ASD youth, particularly those with co-occurring psychiatric disorders, and to refine information on the durability, dose and sub-population effects of the intervention.

The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) Study

A study in Finland found that a multidomain intervention of physical activity, nutritional guidance, cognitive training, social activities and management of vascular risk factors slowed cognitive decline in healthy older adults at increased risk of cognitive decline. A 6-month pilot study was initiated in Singapore, which demonstrated the cultural feasibility and practicality of the FINGER interventions and a set of locally adapted interventions in an Asian population. The SINGER study is a 2-year randomized controlled trial that aims to test the efficacy and safety of these lifestyle changes, including diet and cardiovascular risk factor management, cognitive and physical exercises, in delaying cognitive decline in older adults at risk of dementia.

Promoting Recovery by Overcoming Self-stigma in Mental Health Disorders With a Narrative Enhancement and Cognitive Therapy (NECT) Group Intervention

This study will evaluate whether Narrative Enhancement and Cognitive Therapy (NECT) can promote recovery among adults living with severe mental health disorders, including substance use disorders. NECT is a structured group intervention that combines education about stigma, cognitive techniques to challenge internalized negative beliefs, and narrative exercises that help participants develop a broader identity beyond their diagnosis. Approximately 106 adults receiving outpatient or day-hospital psychiatric care at Geneva University Hospitals will be randomly assigned to receive either usual care plus 12 weekly NECT sessions or usual care plus 12 comparison group sessions that do not specifically address self-stigma or recovery. The study will examine whether NECT improves recovery after the intervention and whether any benefits are maintained over time.

Reducing Stigma Among Healthcare Providers to Improve Mental Health Services

A growing number of trials have demonstrated treatment effectiveness for people with mental illness (PWMI) by non-specialist providers, such as primary care and community health workers, in low-resource settings. A barrier to scaling up these evidence-based practices is the limited uptake from trainings into service provision and lack of fidelity to evidence-based practices among non-specialists. This arises, in part, from stigma among non-specialists against PWMI. Therefore, interventions are needed to address attitudes among non-specialists. To address this gap, REducing Stigma among HeAlthcare Providers to improvE Mental Health services (RESHAPE-mh), is an intervention for non-specialists in which social contact with PWMI is added to training and supervision programs. A pilot cluster randomized control trial will address primary objectives including trainees' perspectives on perceived acceptability of PWMI's participation in training and supervision, intervention fidelity and contagion, assessment of randomization, and feasibility and psychometric properties of outcome measures in a cluster design. Secondary objectives are change in provider and patient outcomes. The control condition is existing mental health training and supervision for non-specialists delivered through the Programme for Improving Mental Healthcare (PRIME), which includes the mental health Global Action Programme (mhGAP) and psychosocial treatments. The intervention condition will incorporate social contact with PWMI into existing PRIME training and supervision. Participants in the pilot will be the direct beneficiaries of training and supervision (i.e., primary care workers) and indirect beneficiaries (i.e., their patients). Primary care workers' outcomes include knowledge (mhGAP knowledge scale), explicit attitudes (mhGAP attitudes and social distance scales), implicit attitudes (Implicit Association Test), and clinical competence (Enhancing Assessment of Common Therapeutic factors, ENACT) to be assessed pre-training, post-training, and at 4-month follow-up. Patient outcomes include functioning, stigma experiences in accessing care, and depression/alcohol use symptoms to be assessed at initiation of mental health care and 6 months later. The pilot study will assist in modifying the intervention to inform a larger effectiveness trial of RESHAPE to ultimately improve provider attitudes and clinical competence as a mechanism to improve patient outcomes.

Immunoinflammatory State Detection and Multimodal Brain Imaging and Electrophysiologic Changes in Schizophrenia

Schizophrenia is a severe mental illness that seriously affects the health and functioning of patients. Previous studies have found immunoinflammatory abnormalities in the blood, cerebrospinal fluid, central nervous system, and neuroimaging of people with schizophrenia, along with therapeutic effects of anti-inflammatory drugs on schizophrenia. These evidences suggest a close relationship between schizophrenia and immunity and inflammation. Therefore, we consider that the state of immune inflammation is a potential subtype classification basis for schizophrenia, and hypothesize that immune classification based on peripheral-central multidimensional data is related to patient's response to medication and cognition.

Co-Creation Workshops With MaKey MaKey to Promote Participation Among People With Mental Health Conditions

This pilot study aims to design, implement, and conduct an initial evaluation of a group-based co-creation workshop program using MaKey MaKey and Scratch for adults attending a mental health day hospital. The program will use low-cost creative technologies as tools to promote social participation, motivation, and empowerment through cooperative experiences adapted to participants' interests, abilities, and needs. The intervention will consist of six weekly sessions lasting approximately 90 minutes each, with the possibility of two additional sessions to complete and present the projects developed. Participants will collaborate in the design of musical activities, cooperative games, interactive narratives, or other creative projects. Assessments will be conducted before and after the intervention, and information will be collected on attendance, participation, usability, incidents, support needs, and adaptations. The feasibility and acceptability of the program, as well as participants' experiences, will also be explored to inform its improvement and potential future implementation in other mental health services.

A Study of XPro1595 in Patients With Early Alzheimer's Disease With Biomarkers of Inflammation

The goal of this Phase 2 Alzheimer's study is to determine whether 1.0 mg/kg XPro1595 confers a benefit on cognition, function, and biomarkers of white matter and to further evaluate safety and tolerability. The objectives of this study are to determine the safety, tolerability, and efficacy of XPro1595 in patients with early ADi.

Stimulation-Induced Changes in Fronto-Limbic Network

The purpose of this research is to better understand how emotion processing unfolds in the brain using stereoelectroencephalography (sEEG) and direct brain stimulation. This study will use standard behavioral emotion processing tasks combined with neural recording and direct brain stimulation to assess different aspects of emotion processing. Stimulation pulses during pre and post-test periods will assess the effects of stimulation before and after conditioning, the results of which will be combined with results from the activity of each electrode during the emotion tasks to inform us of the nature of emotion processing in the brain and allow us to devise brain modulation protocols in the future.

A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer's Disease (TRAILBLAZER-ALZ 6)

This study will investigate different donanemab dosing regimens and their effect on the frequency and severity of ARIA-E in adults with early symptomatic Alzheimer's disease (AD) and explore participant characteristics that might predict risk of ARIA. Approximately 375 additional participants will be enrolled in addendum 2. Addendum 3 includes a subset of participants from the main study to receive a single dose. The study will last approximately 91 weeks and include up to 26 visits in the main study.