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Harvard researcher looks for the key to understanding the link between Down syndrome and Alzheimer’s disease
The link between Down syndrome and Alzheimer’s disease has become the subject of increasing scientific interest, and a major new study is seeking to shed further light on that connection.
Dr. Florence Lai of Harvard University, McLean Hospital in Belmont, and Massachusetts General Hospital, is the lead Massachusetts investigator in a multi-center, five-year study funded by the National Institutes of Health.
Dr. Florence Lai
In an interview with COFAR, Dr. Lai said the study is seeking “biomarkers” that may predict the onset of Alzheimer’s disease and enable researchers to learn more about Down syndrome. It is intended to be “the most comprehensive study of the links between Down syndrome and Alzheimer’s disease up to this point.”
Lai and her colleagues, Dr. Diana Rosas, a neurologist, and Dr. Margaret Pulsifer, a psychologist, are in charge of the Massachusetts portion of the study.
While the average person with Down syndrome develops symptoms of Alzheimer’s disease in their early 50’s, some may not develop the dementia until the age of 70, and a very few escape it altogether.
“The study seeks, among other things, to learn the reasons for that variation,” Dr. Lai said.
The Massachusetts General Hospital’s facility at the Charlestown Navy Yard is one of seven sites around the country and England that are coordinating their research efforts as part of the study. The other sites include Columbia University (New York City), the University of California Irvine, the University of Pittsburgh, Cambridge University (UK), the University of Arizona (Phoenix), and the University of Wisconsin (Madison).
The NIH study represents a natural progression in Dr. Lai’s clinical practice and research. Over several decades, she has evaluated and followed some 750 individuals with Down syndrome, including Joanna Bezubka, a cousin of COFAR Board member and former president, George Mavridis. In 2013, Mavridis published a compelling memoir about his experience in caring for Joanna, who died of Alzheimer’s disease in 2012 at the age of 60.
George Mavridis and Joanna Bezubka on Joanna’s 60th birthday. Joanna, who had Down Syndrome, died in 2012 at the age of 60 of Alzheimer’s Disease. She had been one of Dr. Lai’s clinical patients.
In a recent letter to Mavridis, Lai said that her hunch that women with Down syndrome who developed menopause early were more likely to develop Alzheimer’s disease earlier, led to an earlier multi-year NIH study by a colleague who proved the hypothesis.
Another hunch of hers that immunological factors in Down syndrome might be involved in Alzheimer’s disease is now the subject of intense scientific interest with many researchers concentrating on neuro-inflammation as a causative factor.
Those avenues of inquiry “may pave the way to think outside the box for potential treatments for AD (Alzheimer’s disease),” Lai wrote to Mavridis.
In her interview with COFAR, Dr. Lai said scientists have discovered that people with Down syndrome are genetically predisposed to create large concentrations in their brains of amyloid protein, which is connected with destruction of brain cells in Alzheimer’s disease.
The gene for the precursor of amyloid protein is located on Chromosome 21. Since people with Down syndrome have an extra copy of Chromosome 21, Dr. Lai explained, they “make the amyloid earlier and more of it. That may be the reason for the high incidence of Alzheimer’s disease in people with Down syndrome.”
In order to learn more about the impact of the amyloid protein and other potential biomarkers of Alzheimer disease, the NIH study is designed to collect a broad range of information from the participants in the study, including information on their health history, cognitive functioning, immune and genetic factors, and daily living activities. The information is obtained from cognitive testing, from blood samples that are sent to specialized labs around the country, and from caregivers of the participants.
The study also includes an MRI brain scan of the subjects and an optional PET scan (Positron Emission Tomography), which involves the introduction of a small dose of radioactive material to examine the presence of amyloid protein in the brain. Another optional part of the study includes analyzing the cerebral spinal fluid obtained from a spinal tap.
The 3-year NIH study is limited to adults over the age of 40 with Down Syndrome at three of the sites (including Charlestown) and over age 25 at the other four sites. At the MGH Charlestown site, the study involves three cycles of visits with each cycle involving two to three visits of up to five hours each. The second and third cycles each take place 16 months after the previous cycle.
Although the study was initially funded in September 2015, it took about a year to “harmonize the procedures at all the sites,” Dr. Lai said, and to receive the necessary approvals from the participating institutions including the Research Review Committee of the Department of Developmental Services in the case of Massachusetts. Lai said the researchers at the seven study sites hope to recruit up to 700 individuals to participate in the study.
Lai said that although the NIH authorized the multi-million dollar study in 2015, the federal agency recently announced that it will be forced to cut some of the funding. She noted that the study is expensive to perform. A large number of specialized personnel is needed, and doing the brain scans is “very costly.”
At the MGH site, about 20 participants have been recruited so far and have been through a preliminary visit, Lai said. They receive a modest payment for their participation. The information collected is anonymous, she said. Even the researchers analyze only coded, aggregate data.
Continuing to treat Down Syndrome patients
Apart from the NIH study, Drs. Lai and Rosas continue to clinically treat, test, and follow the life histories of patients with Down syndrome at McLean hospital. They see each patient once a year and generate neurological evaluations which are shared with caregivers and family.
Lai has collected hundreds of blood samples, some of which have been stored at a Harvard-affiliated facility at -80 degrees C. However, the samples have lain dormant for many years due to a lack of funding needed to analyze them. Lai noted that many of her colleagues have experienced the same funding frustrations, and have had to supplement federal funding with industry grants and philanthropic donations.
It was actually due to the generosity of several families of her patients, Lai said, that she herself was able to start a Down Syndrome Fund for Alzheimer Research at MGH. The Fund got a boost of several thousand dollars a few years ago when a member of the MGH Board of Directors called Lai to thank her for her care of a patient with Down syndrome whom he knew personally.
Lai said that if the Down Syndrome Fund ever does get more sizeable contributions, her “dream” is to team up with colleagues to fully analyze the stored blood samples, and “to encourage a younger generation of clinicians and investigators to devote their energies to care for and study those with Down syndrome.”
Persons interested in learning more about the NIH study at MGH can call 617-726-9045 or 617-724-2227.
Those interested in an evaluation and follow-up with Drs. Lai and Rosas at the McLean Hospital Aging and Developmental Disabilities Clinic can call 617-855-2354.
The story of a remarkable woman
I never met Joanna Bezubka, who lived at the Fernald Developmental Center for 39 years and then spent the final seven years of her life in a state-operated group home in Lynnfield.
But after reading “Joanna, God’s Special Child,” a new memoir by George Mavridis, I feel I got to know her well enough that I’m sad I never will meet her in the flesh. That’s because Mavridis, Joanna’s cousin and co-guardian, has written an account of her life that makes you realize what a truly remarkable person she was — filled with charm and humor and an independent spirit.
These are qualities that many of us would not think possible in a person with a profound intellectual disability whose vocabulary was limited to about 50 words and a small range of vocal inflections. Joanna, who had Down syndrome and the cognitive ability of a two-year-old child, died in January 2012 at the age of 60 after developing Alzheimer’s disease.
Given its title, some people might think this book comes at its subject from a religious or sentimental perspective. It is neither of those. As Mavridis explains, “God’s special children” was a description given in the 1950’s by Richard Cardinal Cushing, Roman Catholic Archbishop of Boston, to individuals with mental retardation, now known as intellectual or developmental disability.
It’s not that Mavridis rejects Cardinal Cushing’s description. Mavridis is in fact a practicing Catholic who pushed hard to allow Joanna to continue attending Mass every Sunday at the Chapel of the Holy Innocents at Fernald, long after she had left the facility as a resident. It’s that Mavridis goes so much further than Cardinal Cushing’s description in telling us who Joanna really was.
George Mavridis and Joanna Bezubka celebrate her 59th birthday
Mavridis, a former president of COFAR and The Fernald League, has chronicled Joanna’s life down to some of the smallest details in a matter-of-fact, journalistic style that is all the more compelling because it deals honestly with the major issues of her life, even some of the most difficult and painful episodes. Those episodes include a sexual assault of Joanna, allegedly by staff in a group home in which she lived, and Mavridis’s dogged pursuit of the investigation of the incident.
It’s important to note that Mavridis is a strong defender of a comprehensive system of care for people with developmental disabilities, including the availability of federally regulated Intermediate Care Facilities (ICFs) for those, like Joanna, who need or needed them. Mavridis has been a central figure in the still-ongoing effort to keep Fernald open. He is also a member of the legislative committee of the VOR, a national advocacy organization for the developmentally disabled, which, like COFAR, supports ICF-level care. As a VOR legislative committee member, Mavridis organizes visits with the health aides of the members of the New England congressional delegation.
But the purpose of Mavridis’s book is not to make a statement on one side or the other in the debate over institutional versus community care. It is rather to chronicle a person’s life and to demonstrate the necessity and effectiveness of advocacy for the most vulnerable among us.
If you are the guardian or family member of a developmentally disabled person and you are looking for help in how to cope and advocate on their behalf, I think this book will be very helpful. I think it would also be helpful to legislators and others who seek a better understanding both of who developmentally disabled people are and what is involved in caring and advocating for them.
If nothing else, this book provides a detailed set of reasons for the importance of a provision in federal law, which states that family members should be seen as the “primary decision-makers” in caring for intellectually disabled persons. As Joanna’s co-guardian and the family member most intimately involved in her life, Mavridis was an a far better position to understand her needs and to act in her best interest than the bureaucrats and even some other advocates who often claimed to know what was best for her.
There is one small but telling incident in the book that illustrates that point particularly well. Joanna was a diminutive woman — only four-foot, four inches tall — and Mavridis bought all her clothes for her. He recounts that he would occasionally hear disapproving comments from Department of Developmental Services staff members that the Disney characters on the sneakers he had bought for her were not appropriate for a woman her age. “I would respond,” he writes, “that they should go to a shoe store and look for a woman’s size 2 1/2 pump with a low heel and buy them for Joanna.”
Joanna’s mother died during a heart operation in 1966 when Joanna was 15 years old. As a result, Mavridis’s mother, Stella, became her guardian, and Mavridis himself became co-guardian in 1991. In later years, Joanna’s brother Ronald Bezubka became a co-guardian along with Mavridis; but as Ronald was living in England, Mavridis remained in charge. In Joanna’s later years, Mavridis would visit her twice a week at her group home and take her to his home in Peabody every Saturday.
Throughout, Joanna’s story is told with warmth and humor, largely because of Mavridis’s clear and obvious love for his cousin. He writes that his mother “always said that I was the brother that a girl feels she could hold under her thumb, and Joanna never let me up.”
We learn, for instance, that although Joanna’s teeth had been removed and her food had to be ground, she was a “gourmet,” who “ate very slowly and savored every morsel.” At Fernald, the staff “served her first and picked up her dishes last, so she had time to enjoy her meals.” She also liked to sip coffee all day long and always had a cup with her, which she invariably perched on the edge of the table. “Many times my mother would move it back, away from the edge,” Mavridis writes, “but Joanna wold move it back with a stern look.”
One of Joanna’s favorite games with people was to ask them to cuff her shirt sleeves. “After you did it, Joanna would straighten the sleeves and ask you to cuff them again. This exercise became endless.” Her favorite activities also included playing with Lego toys and tearing paper into ever smaller pieces. Mavridis found he was obliged to carry a supply of both Lego pieces and pieces of paper with him because Joanna liked to hand out both as tokens of friendship to anyone who came by her.
Playing the shirt-sleeve cuffing game
Mavridis also speaks frankly about his own quadruple coronary artery bypass operation, which happened in the same year as the sexual assault, and the effect of his temporary incapacitation on Joanna. He also details Joanna’s physical and mental decline beginning in 2008, when she developed Alzheimer’s Disease, a condition which afflicts nearly all people with Down syndrome as they age.
Mavridis relates how sad it was for him to watch Joanna’s limited ability to communicate disappear in her final four years. She stopped tearing paper and she stopped playing with Legos and handing them out as tokens. Mavridis nevertheless was determined to make her life as comfortable as possible and bought special lift equipment for her as well as a special hospital bed and recliner.
“I bet I blinked first,” Mavridis says of this photo.
Near the start of his book, Mavridis includes a short article by a writer, Emily Perl Kingsley, about what parents go through when they first learn that their child is intellectually disabled. “When you’re going to have a baby, it’s like planning a fabulous vacation trip to Italy,” Kingsley writes. Instead, the plane lands in Holland.
“The important thing is that they haven’t taken you to a horrible place,” Kingsley continues. “It’s just a different place, so you must go out and buy new guide books and you must learn a whole new language…but after you’ve been there for a while…you begin to notice that Holland has windmills; Holland has tulips; Holland even has Rembrandts.”
“Joanna, God’s Special Child” is the story of a wonderful journey to Holland for Mavridis and his family, and of their discovery of the windmills, tulips, and Rembrandts there.
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