Newswise–Most patients with Alzheimer’s disease and Alzheimer’s disease-related dementias experience the gradual onset and progression of cognitive symptoms, leading to decline over years or decades.
However, in a small subset of patients, symptoms begin rapidly, leading to dementia within one year and complete incapacitation within two years of symptom onset. A new study at the Mayo Clinic aims to determine why patients with Alzheimer’s disease and related dementias develop this rapidly progressive dementia.
“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 progressive dementia through a project funded by the National Institute on Aging of the National Institutes of Health.
Specifically, the research team and collaborators aim to:
Determine the factors that make patients with Alzheimer’s disease susceptible to progressive dementia.
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 related dementias.
Identify cellular pathways that contribute to rapid declines in patients with Alzheimer’s disease and dementias.
The researchers plan to collect clinical and genomic information from 120 diverse patients with rapidly progressive Alzheimer’s disease and dementia over the next three years. Findings in patients with progressive dementia, identified through Alzheimer’s Disease Research Centers studies nationally, will be compared with data from participants with typical progressive-related dementias 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. 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. Results will be extended to identify biomarkers and disease-modifying targets that may improve the diagnosis and treatment of patients with the disease.
“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.
The 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.
