The Alzheimer’s Innovation Fund at Brigham and Women’s Hospital

A message from Reisa Sperling, MD, MMSc, director, BWH Center for Alzheimer Research and Treatment and professor of neurology, Harvard Medical School

The Alzheimer’s Innovation Fund at Brigham and Women’s Hospital (BWH) provides critical seed funding to promising research projects aimed at Alzheimer’s prevention. Founded in 2016 by the Vettel family and bolstered by the generosity of many additional supporters, the fund has already served as a remarkable catalyst for groundbreaking research projects spanning from basic science to innovative care delivery.

2017 Project Updates

Understanding the Impact of Sleep and Activity Levels in Alzheimer’s Disease
Lead Investigator: Jasmeer Chhatwal, MD, PhD
Instructor in Neurology, Massachusetts General Hospital
Assistant Professor in Neurology, Harvard Medical School, Massachusetts General Hospital

Previous research has shown that poor sleep quality and decreased levels of daytime activity are associated with a greater likelihood of cognitive decline, as well as increased buildup in the brain of amyloid protein, one of the primary factors in the development and progression of Alzheimer’s disease (AD). Because data on nighttime sleep and other measures has been limited or derived largely from self-reporting, it remains difficult to draw firm conclusions on this association. Now, thanks to new technologies and brain imaging techniques, Dr. Chhatwal and colleagues are positioned to explore these associations more closely than ever before. The team is measuring sleep and activity in a home-based setting using wearable biosensor devices (similar to a Fitbit, but with sophisticated sensors and optimized for detecting sleep patterns), a detailed sleep and activity journal, and an at-home sleep study. They will pair this information with imaging measures of AD protein buildup to provide a firmer basis for assessing how sleep and activity levels relate to AD biomarkers, neural network function, memory consolidation, and cognitive trajectories. The resulting data may provide key clues in identifying populations at high risk for cognitive decline.

 

The Brain Health Champion Initiative
Lead Investigator: Seth Gale, MD
Behavioral Neurologist, Brigham and Women’s Hospital
Instructor in Neurology, Harvard Medical School

Evidence has shown that certain behavior and lifestyle changes, such as increased physical and mental activity, adoption of specific dietary habits, and stress reduction can positively impact brain health. As Alzheimer’s research increasingly moves toward prevention, a model is needed to incorporate this knowledge into patient care. With this in mind, Dr. Gale is assessing the use of specially trained brain health champions (BHCs) to actively engage patients and their families in adopting healthier lifestyles and participating in activities known to promote brain health. BHCs provide individualized support to patients by encouraging and monitoring progress, offering weekly feedback, and serving as a liaison between patients and their clinicians. BHCs also play a critical role in the collection of research data comparing the impact of this innovative program to the standard of care. In early 2017, Hope Schwartz (Harvard College, ’16) became the first BHC, launching what is now a two-year pilot phase involving up to 60 patients. Ultimately, the goal is to improve patient care and clinical outcomes, both for patients with Alzheimer’s disease and people with elevated risk for developing the disease.

 

Developing an Early Biomarker for Cognitive Decline
Lead Investigator: Soyon Hong, PhD
Research Fellow in Neurology, Boston Children’s Hospital and Brigham and Women’s Hospital

Studies have shown that GM1 ganglioside-bound amyloid beta (GAβ)—a form of the amyloid beta (Abeta) protein that is bound to lipids and believed to play a causal role in Alzheimer’s disease (AD)—contributes to synaptic dysfunction in AD. Dr. Hong and her colleagues have found that the formation of GAβ may be one of the first toxic events to occur in the AD cascade, setting the stage for other toxic forms of Abeta such as Abeta 42, which is associated with the hallmark cognitive decline of AD. The research team is now working to characterize GAβ in detail in humans for the first time, with the goal of developing a reliable biomarker at the earliest stages of disease. Using sophisticated new technology, Dr. Hong is developing highly sensitive, single molecule assays to detect GAβ in cerebrospinal fluid (CSF) samples from patients with mild cognitive impairment (MCI) as well as memory-impaired non-MCI patients. She has found that GAβ levels in CSF correlate with levels of Abeta 42, raising its potential as a biomarker for cognitive decline before symptoms even develop.

 

Using Novel Imaging Methods to Identify and Target Toxic Abeta Protein in the Brain
Lead Investigator: Ming Jin, PhD
Investigator, Brigham and Women’s Hospital
Instructor in Neurology, Brigham and Women’s Hospital

Amyloid beta (Abeta) protein is believed to play a key causal role in Alzheimer’s disease (AD), but the various forms of Abeta and their distinct underlying mechanisms are not well understood. Using a sophisticated new technology—the IncuCyte Imaging System—Dr. Jin and colleagues aim to determine which forms of Abeta are most toxic to the brain, opening up new pathways to target those forms for treatment. The IncuCyte camera provides a high-throughput, live-cell imaging platform that allows researchers to examine the effects of AD extracts on neurons and related processes. Through a pilot effort presented at the Society for Neuroscience Annual Meeting in November 2016, the team showed that soluble forms of brain-derived Abeta caused disease-relevant changes that could help investigators identify the most toxic forms. Dr. Jin will continue this line of research by leveraging the IncuCyte paradigm, which provides an excellent tool for the discovery and optimization of potential new therapeutics, such as anti-amyloid antibodies, as well as future efforts aimed at prevention.

 

Assessment of Smartphone Everyday Tasks (ASSET) in Alzheimer’s Disease
Lead Investigator: Gad A. Marshall, MD
Associate Medical Director of Clinical Trials, BWH Center for Alzheimer Research and Treatment
Assistant Professor of Neurology, Harvard Medical School

Impairment in instrumental activities of daily living (IADL)—which range from performing household chores, to driving, to managing finances—is a hallmark of Alzheimer’s disease (AD) dementia, a major contributor to AD-related costs, and a significant source of physical, psychological, and financial burden for patients and caregivers alike. While tools exist to assess IADL at the stage of dementia, we lack a sensitive, real-world test of IADL changes that can be detected in earlier stages of AD, including mild cognitive impairment (MCI) and preclinical AD. Dr. Marshall is addressing this knowledge gap by introducing an innovative smartphone app to detect changes in IADL at the earliest stages of AD. With this app, Dr. Marshall will assess general familiarity with smartphone use, as well as the ability to perform tasks on a patient portal and enter appointments into a calendar. For physicians, the detailed information gathered by the app—being piloted this summer—will provide an easy method to monitor clinical changes remotely and help inform individualized care. The novel app will also enhance clinical trials aimed at finding the earliest possible treatments and provide vital information to investigators working to prevent AD altogether.

The initial seed funding provided by the Alzheimer’s Innovation Fund has already been leveraged to secure an anonymous gift of $100,000 to further support the assessment and use of this technology, which holds great potential to improve the lives of patients, families, and caregivers.

 

A New Model: Improving Care and Fueling Clinical Research
Lead Investigator: Scott McGinnis, MD
Associate Neurologist, Brigham and Women’s Hospital
Assistant Professor of Neurology, Harvard Medical School

There are currently no explicit guidelines for assessing and managing Alzheimer’s disease at every stage of the illness. For example, patients with subjective cognitive decline should be followed and offered available prevention clinical trials and studies―something that often occurs only if a patient visits an expert clinical center. Over the next year, Dr. McGinnis and colleagues will be designing and testing an integrated clinic program to optimize care for patients and further facilitate clinical research efforts. The integrated clinic will provide a Clinical Roadmap to Care, including guidelines for the highest standard of care in a comprehensive fashion, including everything from pharmacological management to counseling and education. Utilizing available IT/programming expertise, this checklist-style approach will be embedded within the electronic medical records system and also help identify patients who are eligible for clinical trials—currently one of the largest hurdles to moving clinical research forward. Once tested and refined locally, the team plans to disseminate the principles and practice of this novel care model to other centers and care settings. This project has been chosen to receive funding and will begin this year.

 

To learn more about the Alzheimer’s Innovation Fund or how to make a gift—including instructions about giving through your donor-advised fund—please contact Ginny Fuller at vgfuller@partners.org or 617-424-4329.