Successful Aging after Elective Surgery (SAGES) II Study Launched

Boston, MA – The Successful Aging after Elective Surgery (SAGES) II study has been launched as a 5-year prospective observational study of 400-420 community dwelling persons, age 65 years and older, prior to scheduled surgery. The study participants are followed during hospitalization through 18 months post-operatively, to examine the pathophysiology and inter-relationship between delirium and dementia using novel biomarkers and cutting edge approaches.  

“We examine novel biomarkers potentially associated with delirium – including inflammation, Alzheimer’s disease (AD) pathology and neurodegeneration, neuroimaging markers, and neurophysiologic markers – and other clinical outcomes,” reports Tammy Hshieh, M.D., M.P.H., one of the first authors.

The SAGES II study lays the groundwork for important future studies based on this comprehensive cohort. According to the researchers, “our overarching hypothesis is that delirium may be a significant initiating and/or predisposing factor for long-term cognitive decline and that patient and hospitalization-specific factors are important additional contributors to delirium and cognitive impairment.” 

The study launch and methods are reported in the paper, “Successful Aging after Elective Surgery II – Study Design and Methods,” published in the Journal of the American Geriatrics Society (October 10, 2022).  The lead authors are Tammy Hshieh, MD, MPH, Assistant Scientist I, Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, Assistant Professor of Medicine, Brigham and Women's Hospital, Assistant Professor of Medicine, Harvard Medical School and Eva Schmitt, Ph.D., Assistant Scientist I, Associate Director, Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research; with Sharon K. Inouye, M.D., M.P.H., Director, Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, Milton and Shirley F. Levy Family Chair Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, senior author and overall principal investigator of SAGES I and II. The goal of this paper is to describe the complex study design and methods for the SAGES II study which integrates MRI, TMS/EEG, PET modalities and high-quality longitudinal data.

According to the paper, “delirium may serve as a marker of pre-existing factors that put patients at increased risk of long-term cognitive decline and dementia. We anticipate that timely interventions and recognition of risk factors for delirium can prevent long-term cognitive decline and dementia, and will ultimately, allow us to improve clinical care for older adults.”

Background 
Delirium is a clinical syndrome characterized by inattention and disturbance in cognition that develops acutely with a fluctuating course. Delirium is a common, serious, and often fatal disorder, associated with increased risk of functional decline, nursing home admission, prolonged length of hospital stay, and cognitive decline. It affects up to 60% of hospitalized seniors, with costs exceeding $204 billion per year (2021 U.S. dollars). The adjusted healthcare costs due to severe delirium in post-operative patients in the U.S. are estimated at $56,474 (95% CI $40,927-$77,440) per patient over one year.  As a preventable condition in 30-50% of cases, delirium holds substantial public health relevance as a target for interventions to prevent its associated burden of downstream complications and costs.

SAGES II represents a comprehensive and advanced study with pre-operative, post-operative and long-term follow-up on a longitudinal cohort of older patients undergoing major surgery. Few studies offer the multi-faceted breadth of assessments of SAGES II, with in-depth clinical characterization, cognitive measures over time, and biomarkers. SAGES II also examines patient-centered outcomes, such as depression, self-rated health, quality of life, and caregiver assessments longitudinally. SAGES II represents a concerted effort to enhance understanding of delirium pathophysiology, an area that remains poorly understood. Moreover, the focus on understanding delirium that leads to long-term cognitive impairment (i.e., complicated delirium) is a major advance, that will allow clinicians and researchers to target interventions for identified risk factors to the most vulnerable patients. Lastly, SAGES I and II will provide a valuable database and biorepository for future research.

According to the authors, the SAGES II study is an important prospective cohort study, and this paper will be the basis for all future work from this innovative gerontological research. Researchers previously studied a cohort of >560 older surgical patients in the Successful Aging after Elective Surgery (SAGES I) Program Project Grant (P01AG031720), and found that delirium was followed by an accelerated trajectory of long-term cognitive decline.  Important risk markers for delirium were elucidated, related to inflammation (Interleukin-6, C-Reactive Protein and Chitinase 3 Like Protein 1), structural dysconnectivity on MRI, and impairment in global cognitive performance. In an effort to validate knowledge of the inter-relationship of delirium and dementia, including the pathophysiology of delirium and its potential linkage to dementia, we proposed the SAGES II study.

Enrollment for SAGES II began on April 1, 2019 and follow-up is ongoing.  Funding is provided by NIA: P01AG031720, R33AG071744, R01AG044518, K24AG035075, R01AG030618, R01AG051658. 

About Hebrew SeniorLife
Hebrew SeniorLife, an affiliate of Harvard Medical School, is a national senior services leader uniquely dedicated to rethinking, researching, and redefining the possibilities of aging. Hebrew SeniorLife cares for more than 3,000 seniors a day across six campuses throughout Greater Boston. Locations include: Hebrew Rehabilitation Center-Boston and Hebrew Rehabilitation Center-NewBridge in Dedham; NewBridge on the Charles, Dedham; Orchard Cove, Canton; Simon C. Fireman Community, Randolph; Center Communities of Brookline, Brookline; and Jack Satter House, Revere. Founded in 1903, Hebrew SeniorLife also conducts influential research into aging at the Hinda and Arthur Marcus Institute for Aging Research, which has a portfolio of more than $63 million, making it the largest gerontological research facility in the U.S. in a clinical setting. It also trains more than 1,000 geriatric care providers each year. For more information about Hebrew SeniorLife, visit our website or follow us on our blog, Facebook, Instagram, Twitter, and LinkedIn.

About the Hinda and Arthur Marcus Institute for Aging Research
Scientists at the Marcus Institute seek to transform the human experience of aging by conducting research that will ensure a life of health, dignity, and productivity into advanced age. The Marcus Institute carries out rigorous studies that discover the mechanisms of age-related disease and disability; lead to the prevention, treatment, and cure of disease; advance the standard of care for older people; and inform public decision-making.