Mayo Clinic researchers are studying why some Alzheimer’s patients decline rapidly, aiming to find causes, biomarkers, and treatments using genomic data, protein analysis, and remote trials funded by the NIH.
Most individuals with Alzheimer’s disease and Alzheimer’s Disease Related Dementias (ADRD) experience a slow, gradual decline in cognitive function over several years or even decades. However, a small subset of patients develop symptoms much more rapidly, progressing to dementia within a year and becoming completely incapacitated within two years of onset. A new study at the Mayo Clinic is investigating the underlying reasons why some patients with Alzheimer’s and ADRD develop this rare and aggressive form, known as rapidly progressive dementia (RPD).
“The factors that give rise to extreme, rapidly progressive clinical traits are unknown,” says Gregg Day, M.D., a neurologist and clinical researcher at Mayo Clinic in Florida. “These cases are challenging to treat in practice because there are many possible causes and diseases to consider, many tests that can be done and a clear need to coordinate evaluations rapidly.”
Dr. Day will lead a team of researchers from Mayo Clinic in Florida and Rochester, Minnesota, to study the biology of RPD through a project funded by the National Institute on Aging of the National Institutes of Health (NIA/NIH).
Goals of the Study
Specifically, the research team and collaborators aim to:
- Determine the factors that make patients with Alzheimer’s disease and ADRD susceptible to RPD.
- Study the contributions of amyloid and tau toxic proteins and vascular changes in the brain to rates of progression in patients with Alzheimer’s disease and ADRD.
- Identify cellular pathways that contribute to rapid declines in patients with Alzheimer’s disease and ADRD.
The researchers plan to collect clinical and genomic information from 120 diverse patients with rapid progressive Alzheimer’s disease and ADRD over the next three years. Findings in patients with RPD, identified through Alzheimer’s Disease Research Centers studies nationally, will be compared with data from participants with typical progressive Alzheimer’s disease and ADRD enrolled in studies at the Alzheimer’s Disease Research Center at Mayo Clinic.
The team hopes to learn how factors such as age, sex, medical history, structural and social determinants of health, genetic variants, and other brain changes may make some patients more susceptible to rapid decline.
Comparing Rapid and Typical Alzheimer’s Progression
Findings will be validated through expansive protein analyses in cerebrospinal fluid from an independent group of patients with autopsy-confirmed rapid progressive Alzheimer’s disease and ADRD. Results will be extended to identify biomarkers and disease-modifying targets that may improve diagnosis and treatment of patients with Alzheimer’s disease and ADRD.
“We hope the results of our research will inform new approaches, diagnostic tests, and treatment targets that will improve outcomes in patients with AD/ADRD. The ultimate goal is to slow down the pathologic progression of disease in these patients, independent of their rate of decline,” says Dr. Day.
The research will combine Mayo Clinic’s expertise in digital innovation and telemedicine to engage patients across the United States.
This study will also leverage Mayo’s Clinical Trials Beyond Walls program, which allows patients to complete some, if not all assessments from the comfort of their own homes or local community facilities. The decentralized clinical trials initiative is designed to remove barriers to clinical trial participation by providing digital solutions and remote services to reimagine the trial experience for all involved, including participants, investigators, study teams, and clinical care providers. Decentralized research ― studies conducted outside the walls of traditional research facilities ― may use a wide range of technologies and services such as telehealth, remote monitoring, mobile phlebotomy, retail pharmacy, and home healthcare.
The research will be made possible through the National Institutes of Health grant award number R01 AG089380.
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