1. What is the Global AGE-BD project (GAGE-BD) and why is it needed?
The GAGE-BD project is an integrated database, combining data from studies of Older Adults with Bipolar Disorder (OABD), defined as BD patients 50 years of age or older, conducted by different sites from around the globe. Sources of data include studies that are ongoing or complete, with at least 20 OABD participants. Data analysis using GAGE-BD is expected to help address knowledge gaps in our understanding of OABD, potentially informing future research and clinical care.
The evolution of bipolar disorder (BD) symptoms and functioning across the lifespan is incompletely understood. Some studies suggest a progressive worsening of symptoms over the course of BD, with more depressive symptoms in older-age BD (OABD) and less psychotic symptoms. Clinical course may differ depending on age at onset, gender, and economic resources. Importantly, deficits of everyday functioning are common in OABD, with mood symptoms, cognitive deficits, and medical conditions all contributing to disability. Predictors of clinical course in OABD have not been clearly articulated so far, however, and findings are primarily based upon data from a limited number of research samples with a relatively narrow geographic and age representation. Knowing how the clinical presentation of BD is expected to evolve as people age is important in order to plan for and provide services that are appropriate, efficient and optimize quality of life. This is particularly imperative due to global demographic trends, including: 1) The world’s population ia aging due to longer life-span and fewer births, 2) People with chronic health conditions (like bipolar disorder) are surviving longer, and are expected to have greater medical comorbidity and burden, and, 3) Healthcare providers and systems will be stretched to accommodate the growing number of older and more complex patients.
Understanding symptom development and outcomes across adulthood will enable anticipation of the needs of people with BD, and fuel development of strategies to modify the course of BD.
2. How is GAGE-BD expected to advance care for patients?
GAGE-BD is combining data elements from studies that are completed or ongoing and use these existing data to investigate important research questions relevant to aging and BD. Examples include querying the data to see how BD symptoms and medical burden may affect functioning as people with BD age. A second component of the GAGE- BD project is to convene a group of investigators committed to study of OABD and to 1) establish consensus on a standardized set of measures/instruments to assess outcomes in OABD and 2) begin laying an infrastructure that is ready to collaborate with other global BD consortia to carry out clinical trials and prospective longitudinal studies.
3. How is GAGE-BD being supported?
The GAGE-BD initiative was initially supported by a 3-year grant from the International Society for Bipolar Disorders (ISBD) Bowden-Massey Strategic Research Initiative. The project is being led by investigators at 4 site/universities: Case Western Reserve University (CWRU) in Cleveland, Ohio, University of California (UC) San Diego, Lady Davis Institute (LDI) of McGill University in Montreal, Canada, and GGZ InGeest in the Netherlands. The continuation of the GAGE-BD project would not have been possible without the generous funding of the Tim and Joan Jenkins Fund, Otsuka, Alkermes and Intra-Cellular Therapies Inc.
4. How much time and effort will participation in this project require?
Participation effort for sites that contribute data varied depending on the study and data. A site investigator needed to supervise a local research assistant to harmonize data, prepare a data dictionary, and prepare data- sharing agreements. There was a modest amount of compensation available to help defray at least a portion of this effort if sites were unable to cover this effort using other resources. The 4 lead GAGE-BD sites (CWRU, UC, LDI, GGZ) provided support in helping sites to ensure that any IRB or regulatory issues were appropriately addressed and that site burden/effort was minimized. Examples of support included instructions on ensuring that data are de-identified, suggested language to use for the informed consent documents for new studies, and sample templates that might be needed for data use agreements or other regulatory purposes.
5. How are decisions about how the data are used be made?
Sites who contribute data to GAGE-BD were invited to name one representative to serve on a Steering Group that decides how the data are used. The GAGE-BD Steering Group establishes consensus on analyses that will be conducted, the order that they will be conducted in, how and where they will be reported, and how authorship should be fairly credited for reports or publications that arises from GAGE-BD analyses. All sites can submit proposals for analysis. The GAGE-BD steering group also makes consensus/incremental decisions regarding establishing procedures more broadly as they arise.
6. What data have been collected so far?
WAVE 1: The first wave of the GAGE-BD project consisted of (total N = 1758), individuals with BD (N = 1368, 86.5%OABD) as well as healthy participants (N = 297) from 19 studies from 13 sites. The data was collected, harmonized and analyzed since March 2020.
WAVE 2: The second wave of the GAGE-BD sample, a completely independent set of men and women (total N = 3062), comprises individuals with BD (N = 2305, 49.9% OABD) and 478 healthy participants from 15 studies and 12 sites. The data is available for data-analyses since March 2022.
WAVE 3: The third wave of the GAGE-BD sample include data from 13 studies from 11 sites including 1461 participants with BD (70.2% OABD), 240 participants with other psychological disorders (e.g., MDD, Schizophrenia, and Schizoaffective) and 112 healthy controls. The data team is finalizing harmonization and expects all data to be available for analyzing 2rd quarter of 2026.
7. What kinds of variables have been collected so far?
You can see some of the variables we have harmonized in our integrated dataset in this table. Another way to peruse the variables that we have available in the integrated dataset is to examine this webpage. There, you can visualize the different variables categorized into domains such as “Clinical Characteristics”, “Demographics”, or “Current Illness Severity.” These visualizations are based on the output of a software program that we developed called VariCat which helps us to categorize and standardize variables from various datasets to allow researchers to query and visualize available measures. You can read more about VariCat and how to use the visualization tool here. “
