The Boston University Alzheimer’s Disease Center (BU ADC) has been selected to participate in a new nationwide clinical trial for the treatment of mild to moderate Alzheimer’s disease (AD). BU ADC investigators will be partnering with Elan and Wyeth pharmaceutical companies, the sponsors of this clinical trial, who developed the new vaccine called bapineuzumab (pronounced bap-e-new‘-zoo-mab).
Bapineuzumab is expected to increase the clearance of beta amyloid from the brain. Beta amyloid is a small protein that leads to the amyloid plaques in the brain of AD patients and is widely believed to be the initial cause of AD. The vaccine used in this clinical trial is referred to as passive immunotherapy. This type of therapeutic approach delivers synthetically engineered anti-amyloid antibodies directly to the participant’s bloodstream with the aim of clearing and preventing beta amyloid accumulation.
In an earlier trial by Elan-Wyeth, mild to moderate AD patients were provided with a synthetic form of the beta amyloid peptide to stimulate the body’s immune response to clear beta amyloid from the brain. Preliminary results indicated observable amyloid plaque clearance, improved memory and cognitive functions, and reduced levels of tau protein (a biological marker known to be elevated in AD) in the cerebral spinal fluid. Researchers believe that the passive immunotherapeutic approach with bapineuzumab may be as effective as active immunization in clearing beta amyloid from the brain. It may also have the added benefit of eliminating the need for patients to stimulate their own immune response to the protein.
“This is an exciting time for AD treatment research,” said Dr. Robert Stern, Co-Director of the BU Alzheimer’s Disease Clinical and Research Program, Associate Director of the BU ADC Clinical Core, and the BU principal investigator for the new vaccine study. “Bapineuzumab is one of several new experimental treatments for AD in phase III clinical trials that may actually help modify the disease process.” The BU ADC has been actively involved in clinical trials for another potential disease modifying drug, Flurizan (Myriad Pharmaceuticals) over the past two years. Results from those trials are expected within one year. For more information regarding studies being conducted at the BU ADC please contact Erin Whalen at 617-414-1078 or firstname.lastname@example.org or visit our website.
International Prevention Conference
June 9- 2, 2007
This conference is for clinicians, researchers, and policy advocates who want a dynamic forum to exchange knowledge about early diagnosis, treatment, and possible prevention of Alzheimer’s disease. www.alz.org/preventionconference
Memory Ride for Alzheimer‘s Research
July 28, 2007
The 11th Annual Memory Ride, sponsored by the Alzheimer’s Association, is a one-day bike ride with three different distance options: 25, 50 and 100 miles. www.memoryride.org
Dementia Care Conference
August 26-29, 2007
This annual conference for dementia care professionals features the latest developments in Alzheimer’s disease care and support.
September 30, 2007
Memory Walk is the signature fundraising event of the Alzheimer’s Association, bringing together family, friends, caregivers, and concerned community members — all wanting to make a difference. To participate on the Boston University Alzheimer’s Disease Center Team or to sponsor our walkers, log onto our website at memorywalkma.kintera.org/2007/buadc
The BU ADC is pleased to welcome Ms. Christine Chaisson as the new Data Core Leader. Ms. Chaisson is an Assistant Research Professor of Public Health (Biostatistics) and Acting Director of the Data Coordinating Center, a data management resource center for Boston University Medical Center. Ms. Chaisson’s team creates and maintains database applications for the BU ADC’s participant registry (i.e., Health Outreach Program for the Elderly) and the Brain Bank. She and her team perform subject tracking, data entry, and data reporting. Ms. Chaisson also assists with form development for data collection, and she creates analytic datasets for BU ADC investigators and trainees.
The BU ADC is pleased to welcome our new staff members: Caleb Bliss, data manager for the Data Core; Mario Orozco, clinical trial participant coordinator; Janet Callaghan, research nurse; and Susan Vanderhill, coordinator for the ADMIRE study and the ADC Education and Information Transfer Core.
We also extend a warm welcome to our new student trainees: Moniek Damman and Welmoed Dekker from the Netherlands and Brian Panichella from Boston College.
The BU ADC would like to congratulate Drs. Carmela Abraham and Benjamin Wolozin for their invited attendance of the 100th anniversary of Dr. Alois Alzheimer’s lecture describing the symptoms and neuropathological examination of Auguste D, the first documented patient to suffer from a disease later named after Dr. Alzheimer. The meeting took place in November 2006 at the Psychiatric Institute in Tubingen, Germany.
BU ADC student trainee Laura Byerly will be joining our staff as a psychometrician for the HOPE study following her graduation from Boston University this spring.
Dr. Robert Green is the recipient of a K24 Mid-Career Investigator Award. Dr. Green will use this five-year NIH grant to discover and quantify ways of characterizing genetic risk for Alzheimer’s disease and to create and evaluate real-world procedures for communicating genetic risk. A major focus of this award is to mentor junior investigators in patient-oriented research.
Dr. Kathy Horvath recently received funding from the VA Health Services Research and Development Program to conduct a clinical trial of a home safety intervention for patients with Alzheimer’s disease. This study will compare the efficacy of two methods of health education on caregiver and care-recipient outcomes.
Valerie Nolen was recently appointed to the National Brain Health Initiative in partnership with the Center for Disease Control.
Many thanks and best wishes to BU ADC faculty and staff who have recently taken on new positions: Suzette Levenson, former Data Core Director, is now Acting Associate Dean of Administration & Finance for the Boston University School of Public Health; Debra Hanna, former clinical research manager, is now completing her PhD in Nursing at the University of Massachusetts at Lowell; Emily Hubbard, former psychometrician, is now completing her Master’s in Public Health at Boston University School of Public Health; Stacy Carruth, former study coordinator, is now serving as a Community Health Specialist at the Regional Center for Healthy Communities; Kate Henderson, former participant coordinator, is now volunteering in public health in Peru; and Judy Hibschman, former HOPE psychometrician, is enrolling in the nurse practitioner program at Columbia University.
Thanks also to our former pre-doctoral trainees, Kevin Blankevoort and Karin Volkers, and postdoctoral trainee, Dr. Hennie Lee, who have all returned to the Netherlands.
Memory & Cognition
HOPE: Health Outreach Program for the Elderly
This longitudinal study increases our understanding of agerelated changes in memory and thinking. It serves as the BU ADC’s main research registry, where participants agree to be contacted regarding other BU ADC-approved studies.
Understanding False Memory in AD
This study seeks to better understand why patients with Alzheimer’s disease (AD) and other dementias frequently remember things that never happened. The ultimate goal of this NIA-sponsored study is to provide the basis for ways to reduce false memories in patients with dementia.
Caregiving Support & Education
This caregiver-based study is seeking to determine whether an educational intervention can reduce behavior problems in patients with AD and improve caregivers’ emotional well-being. It consists of a 5-week group intervention which offers 90-minute weekly sessions on AD, its symptoms, and tips for improving communication and interactions with the family member. It also focuses on family members’ feelings about their own caregiving skills. The individual with AD is not involved in this study.
MIRAGE: Multi-Institutional Research in Alzheimer‘s Genetic Epidemiology
This longstanding study evaluates the association between genetic (hereditary) and non-genetic risk factors for AD. The study is currently recruiting people with a diagnosis of probable AD who also have an unaffected sibling who would be willing to participate with them. The study is being conducted at multiple sites in the United States and abroad.
REVEAL III: Risk Evaluation and Education for Alzheimer‘s Disease
This study is a multi-center, nationwide research project. The goal of REVEAL-III is to provide healthy adults with genetic susceptibility testing and information about their chances to develop AD.
DHA (new study)
This new study is a multi-center clinical trial that will evaluate the effectiveness of a new medication, DHA, in slowing the progression of AD. The study is recruiting participants with mild to moderate AD who have a caregiver available to accompany them to clinic visits.
For more information, please call the recruitment coordinator, Erin Whalen, at 617 414-1078
Early Alzheimer‘s Neuropathological Changes Observed in Posterior Cortex
Dr. Ann McKee was selected to present “Early Tau Alterations are Prominent in Posterior Association Cortex in Preclinical Alzheimer’s Disease” as a platform presentation at the American Academy of Neurology meeting, scheduled April 28th-May 5th. Over 10,000 researchers attend this annual national meeting. Dr. McKee’s research study, using the BU ADC Brain Bank, identified major biological changes in early stage Alzheimer’s disease in an area of the brain that has previously been overlooked. Collaborators of this project include investigators and staff from the Framingham Heart Study, including Dr. Philip Wolf, Dr. Rhoda Au, Jonathan Drake, Hyo Lee, and Carol Kubilus, and BU ADC Director, Dr. Neil Kowall.
Advancement in Tracking Brain Response to Drug Therapy
Dr. Brandon Ally, an investigator in Dr. Andrew Budson’s Cognitive Neuroscience Laboratory, was awarded a 2006 ADC Pilot Grant to investigate electrophysiological biomarkers of patient response to drug therapy. Preliminary results are promising, illustrating that areas of the brain critical to memory function show an improved response after 8 weeks of cholinesterase inhibitor therapy. Figure A shows the brain activity of Alzheimer’s disease patients prior to beginning therapy. Figure B shows improved brain activation after 8 weeks of therapy. The laboratory is continuing to recruit participants for this study.
New Drug Target for Alzheimer‘s Disease
Drs. Rina Yamin and Carmela Abraham reported in the Journal of Neurochemistry on the discovery of a novel enzyme, APEH, that can remove the toxic amyloid protein. There is ample evidence that the amyloid protein plays a major role in the development of Alzheimer’s disease pathology and symptoms. Currently, the normal function of this enzyme is unknown, but studies using brain tissues from the BU ADC Brain Bank demonstrate that the level of the enzyme in Alzheimer’s disease brains is five times lower than that found in healthy age-matched controls. Thus, APEH may become a new therapeutic target for Alzheimer’s disease. Reference: Yamin, R, Bagchi, S, Hildebrant, R, Scaloni, A, Widom, RL, and Abraham, CR. Acyl Peptide Hydrolase, a Serine Proteinase Isolated from Conditioned Medium of Neuroblastoma Cells, Degrades the Amyloid ÃŸ Peptide. Journal of Neurochemistry, 2007; 100:458-467.
Race and Self-Perceived Risk for Alzheimer‘s Disease Associated with Study Dropout
Dr. Anil Nair’s abstract, “Race and Low Self-Perceived Risk for Alzheimer’s Disease are Associated with Higher Dropout in REVEAL study,” was selected as a platform presentation at the International Conference on Prevention of Dementia. This meeting will be held in Washington, DC, June 9th-12th. Findings from this study suggest that race and lower self-perceived risk are associated with increased study dropout among family members of Alzheimer’s disease patients who choose to get genetic susceptibility testing. Collaborators of this project include BU ADC investigators and staff, including Susan Hiraki, Winston Chung, Clara Chen and the BU ADC Clinical Core Director, Dr. Robert Green.
In this issue of the BU ADC Bulletin, we are pleased to highlight the opening of two new BU ADC-affiliated clinics, including the Alzheimer‘s Disease Clinical & Research Program Clinic at Boston University Medical Center in Boston, MA and the Edith Nourse Rogers Memorial Veterans Hospital Geriatric Research, Education, & Clinical Center Memory Diagnostic Clinic in Bedford, MA. These services are in addition to those already offered by BU ADC-affiliated clinics at Boston University Neurology Associates in Boston, MA and Weymouth, MA. For more information on all BU ADC-affiliated clinics, log onto our website (www. bu.edu/alzresearch).
Alzheimer‘s Disease Clinical & Research Program Clinic at the Boston University Medical Center, Boston, MA
Dr. Robert Stern (neuropsychologist), Dr. Anil Nair (neurologist), and Mr. Eric Steinberg (nurse practitioner) provide compassionate care for older adults with memory complaints and other cognitive problems at the Alzheimer‘s Disease Clinical & Research Program (ADCRP) Clinic. This team of experienced and knowledgeable professionals provides a comprehensive evaluation, which includes extensive interviews with the patient and family members, neuropsychological assessment (such as tests of memory and language), a neurological examination, and related diagnostic tests (such as brain imaging and blood work).
In most circumstances, all aspects of the clinical evaluation are conducted on the same day. An additional appointment is held one or two weeks later to review the results of the evaluation and treatment recommendations with the patient and family members.
The ADCRP Clinic provides medical treatment and follow-up care for Alzheimer’s disease, frontal dementias, Lewy body disease and related disorders. This clinic also provides assessment of the cognitive and thinking skills necessary for safe driving along with consultation and support for the patient and family about the difficult decision to stop driving.
In addition to assessment services, the clinic provides assistance to patients and their families for long-term care planning, caregiver support, education, and referrals for community resources, such as adult day programs. These clinical services are affiliated with the research component of the ADCRP, which carries out many clinical trials in Alzheimer’s disease. These trials provide interested patients with the opportunity to participate in cutting edge Alzheimer’s research.
The ADCRP Clinic welcomes new referrals from patients, families, or health care providers. To request an appointment or make a referral, please call 617-638-7100.
The Memory Diagnostic Clinic at the Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA
The Edith Nourse Rogers Memorial Veterans Hospital is pleased to announce that their new Memory Diagnostic Clinic is open and accepting new veteran referrals. The Memory Diagnostic Clinic, headed by Dr. Maureen O’Connor (neuropsychologist) and Dr. Andrew Budson (neurologist), provides comprehensive evaluation, diagnosis, and treatment of adults with Alzheimer’s disease, dementia, and other related memory disorders. The multidisciplinary team consists of neurologists, neuropsychologists, and nurse practitioners who are experts in the diagnosis and treatment of memory disorders, and who are committed to enhancing the knowledge of the patient, caregivers, medical professionals, and the public through both clinical and research methods. An evaluation typically takes place in one day over the course of several hours and includes a neurological examination, a neuropsychological evaluation, laboratory assessments and neuroimaging tests as needed.
When all tests are completed the patient is scheduled for a return visit to review results from the evaluation, ask questions, and receive treatment recommendations. The Memory Diagnostic Clinic provides education and information to patients and their caregivers concerning diagnosis, family planning, and patient care. This clinic also offers interventions for patients and caregivers as appropriate, including time limited individual and family psychoeducation, cognitive rehabilitation, and caregiver groups. In addition, linkage to community resources for additional care is provided.
The Memory Diagnostic Clinic welcomes new referrals. You must be a veteran to be seen in this clinic. The clinic is open Mondays from 9am to 3pm. For general information please contact Victoria Henehan at 781-687-3240, Monday through Friday, 8:00am – 4:30pm.
In conjunction with colleagues from the University of Toronto and Columbia University, senior researchers affiliated with the Boston University Alzheimer’s Disease Center have uncovered a major new gene associated with Alzheimer’s disease (AD). Published in the February 2007 issue of Nature Genetics, data from four different ethnic groups support a link between the SORL1 gene and late-onset AD. This discovery is only the second gene to be linked to late-onset AD. Apolipoprotein E (APOE), identified in 1993, was the first late-onset AD gene to be discovered.
This new genetic discovery was uncovered when the international research group found that variants of the SORL1 gene are more common among people with late-onset AD as compared to healthy adults of the same age. The international research team believes that these SORL1 variations may be more common in people with AD because the SORL1 gene is functioning improperly. Through the amyloid precursor protein, SORL1 may increase amyloid beta peptides in the brain. Increased amyloid beta peptides are a key neuropathological feature of AD.
The SORL1 finding is based on a five-year study that involved DNA samples from more than 6,000 research volunteers. These data are particularly unique because most prior studies on the genetics of AD have focused on White populations of European ancestry. In contrast, the SORL1 discovery was replicated across four distinct ethnic and racial groups, including Whites of European ancestry, African-Americans, Caribbean-Hispanics, and Israeli-Arabs.
Dr. Lindsay Farrer, Chief of the Genetics Program at Boston University School of Medicine, led the local research effort. The University of Toronto research team was led by Dr. Peter St. George-Hyslop, Director of the Centre for Research in Neurodegenerative Diseases, and the Columbia University Medical Center research team was led by Dr. Richard Mayeux, Co-Director of the Taub Institute of Research on Alzheimer’s Disease and the Aging Brain.
In March, Dr. St. George-Hyslop presented the SORL1 research findings at the Boston University Alzheimer’s Disease Center lecture series, where he emphasized that additional data supporting SORL1’s association with AD are needed. “This finding demonstrates the importance of international collaboration and is exciting preliminary information that needs to be validated.”
Dr. Farrer believes this discovery is an important advancement in the understanding of genetics and AD, but he cautions that much more work lies ahead. “While we have identified several variants in SORL1 that show the same pattern of association across multiple ethnic groups with very different genetic makeup and lifestyle characteristics, we have not yet discovered the mechanism linking SORL1 gene variants to altered functioning of the SORL1 protein that may accelerate the process leading to AD.”
On Tuesday, January 16, 2007, Dr. Robert Green, Director of the Boston University Alzheimer’s Disease Center (BU ADC) Clinical Core, and Dr. Robert Stern, Associate Director of the BU ADC Clinical Core, gave a joint presentation to the Bipartisan Congressional Task Force on Alzheimer’s Disease. Dr. Green gave an overview of Alzheimer’s disease (AD), and he spoke about risk factors relating to AD in special populations. Dr. Green also presented new findings in the genetics of AD (see “New Alzheimer’s Gene Discovery” feature article in this issue). Dr. Stern presented information pertaining to recent advances in the diagnosis and treatment of AD as well as the important public health issue of AD among minority populations. In particular, he emphasized the need to diminish health care and research disparities among African-American elders.
Both Drs. Green and Stern emphasized the critical need to increase National Institutes of Health (NIH) funding for AD research. Former BU ADC trainee Dapo Akinleye discussed the importance of an NIH diversity training grant that supported a portion of his graduate education. He received his Master’s in Public Health from the Boston University School of Public Health while working with Dr. Green at the BU ADC. Mr. Akinleye described to the Congressional Task Force his experiences working in the African-American community and methods for overcoming the reluctance of this population to seek medical care for this devastating disease.
Massachusetts Congressman Edward Markey, who invited the BU ADC researchers to present at the Congressional briefing, expressed his appreciation to the speakers and provided strong support for the need for increased federal funding of AD research and clinical care. Congressman Markey has been a leading national advocate for new grant programs for AD research and additional funding for the NIH.
“This invitation was an honor for our entire institution as it recognized the groundbreaking work in AD being carried out at Boston University Medical Center,” said Dr. Green. “The experience of briefing Congress also gave us a rare opportunity to speak directly to the people who are deliberating about the NIH budget, particularly funding for AD, about the critical need for increased funding at this time. We appreciate the leadership of Congressman Markey in rallying efforts to preserve and extend research to defeat AD.”
The BU ADC welcomes Dr. Hennie Lee, a post-doctoral research fellow who trained at the University of Amsterdam and was a resident neurologist in the Netherlands. Dr. Lee evaluates patients for Alzheimer’s disease research studies.
A warm welcome to our new ADC Staff: David Essaff, MS, ADNI Study project coordinator; Judy Hibschman, HOPE psychometrician; Susan Hiraki, MS, REVEAL Study genetic counselor and project manager; Carol Rossi, RN, clinical research manager; Michael Wake, MSW, MIRAGE Study project manager; Megan Wulff, ADAPT psychometrician.
We are also happy to work with the following new trainees: Kevin Blankevoort and Karin Volkers, from the Netherlands; Megan Campbell, Suffolk University doctoral student; Winston Chung, BU medical student; Dan Daneshvar, Lindsey Grace, and Meghan Lembeck, all students of the BU Graduate Medical Sciences Program; Megan Grace, Boston College student.
We are pleased to announce that Dr. Robert Stern has recently been named Co-Director of the Alzheimer’s Disease Clinical & Research Program at Boston University
Many thanks to the following staff who have completed work at the BU ADC:
Scott Roberts, PhD, who served as Education Core Co-Director, Early Stage Project PI, and co-PI of the REVEAL study, is now an Assistant Professor at the University of Michigan; Danya Goodman, former HOPE psychometrician, is now a clinical psychology doctoral student; Jennifer Hunter, former research coordinator for the Driving Study is with the California Department of Public Health; Susan Lambe, former ADMIRE coordinator, is a doctoral student in clinical psychology; Erin Linnenbringer, genetic counselor and project manager for REVEAL, is a doctoral student at the University of Michigan; Sulaiman Sanni is completing studies at Boston College; Sarah Wong, an ADMIRE study research assistant, enrolled at the Tufts School of Medicine.
Dr. Anil Nair recently joined the Alzheimer’s Disease Center as an Assistant Professor of Neurology and as an attending neurologist at Boston Medical Center. Dr. Nair completed his medical training and general internal medicine residency at JIPMER, Pondicherry University, followed by a neurology residency at Temple University and the Cleveland Clinic. Dr. Nair completed fellowship training in behavioral neurology at the Mayo Clinic under Dr. Ronald Peterson. A recipient of the National Talent Search Scholarship and Genesis Award in computational design, Dr. Nair’s research interest includes MCI, AD, Lewy Body dementia, vascular dementia, and dementia patients’ quality of life. Dr. Nair will serve as investigator for the HOPE and REVEAL studies and ongoing AD patient treatment trials, and see patients with memory disorders.
New Memory Clinics
A new Memory Diagnostic Clinic is starting at the Edith Nourse Rogers Memorial Veterans Hospital in Bedford by Drs. Maureen O’Connor and Andrew Budson. Neuropsychologists, neurologists, and nurse practitioners will perform evaluations and serve veterans with memory concerns. For information or to schedule appointments, contact Dr. O’Connor at 781-687-2830.
Dr. Robert Stern, Alzheimer’s Disease Clinical & Research Program Co-Director and Director of Neuropsychology, is accepting referrals for neuropsychological evaluations at the Boston BU Medical Campus. Services include formal cognitive assessments and consultation for patients with known or suspected memory disorders as well as counseling and guidance to caregivers of persons with dementia. Cognitive assessments of driving safety-related skills will also be offered. To make a referral or schedule appointments, call 617-638-7100.