A new report from an expert workgroup, published in the journal Alzheimer’s & Dementia, sheds light on what is considered clinically meaningful in the fight against Alzheimer’s disease. The report emphasises the importance of slowing the progression of the disease, rather than solely trying to halt it.
The report highlights the benefits of slowing Alzheimer’s progression, especially in the early stages when patients still retain much of their cognitive abilities and memory. The findings suggest that a statistically significant benefit seen in an 18-month clinical trial could lead to an even greater impact over time.
In addition, the report stresses the importance of combination therapies in effectively treating Alzheimer’s. The workgroup believes that no single intervention will have a major clinical impact on its own and that a combination approach, similar to that used for treating high blood pressure and cancer, will be necessary to achieve greater results.
Alzheimer’s disease often begins to attack the brain long before a person begins to show symptoms like memory loss and thinking problems. While clinical trials for disease-modifying therapies usually only last 18 months, the report considers how best to assess the significance of slowing the disease’s progression in a way that is meaningful to patients, families, and the scientific community.
“Slowing brain deterioration even four to six months in the early stages of Alzheimer’s disease may lead to preservation of function for patients that can be very meaningful to patients and their families,” said Ronald Petersen, MD, Mayo Clinic neurologist, a work group member and lead author of the journal article. “The longer someone is able to delay loss of independence and to continue to participate in daily activities, the more meaningful these results become.”
Complex disease process
Changes in the brain from Alzheimer’s disease do not happen in isolation. Someone who is cognitively impaired typically has other neurodegeneration processes occurring at the same time.
Over the course of an 18-month clinical trial, “the observed clinical impact of a single intervention is reasonably expected to be quite modest,” the authors write. However, if therapy is continued longer and its effectiveness is sustained, cumulative benefits will become more apparent.
The work group notes that just as high blood pressure and cancer are treated with multiple medications, so too will multiple therapeutic interventions be needed to address complex brain changes and related memory and thinking problems.
“The work group recognized that we need to modify expectations of a single intervention on a complex set of neurodegenerative processes, but recent progress with newly approved Alzheimer’s drugs is a tremendous first step,” Dr Petersen explained.
About clinical meaningfulness
A 2021 article from the Alzheimer’s Association Research Roundtable referenced the Food and Drug Administration’s description of clinical meaningfulness as when “the treatment has a positive and significant effect on how an individual feels, functions, or survives.”
Interpretation of clinical meaningfulness will be part of discussions clinicians will have with patients and their families when they are considering potential benefits, risks and challenges of disease-modifying therapies newly approved to treat Alzheimer’s disease.
“It’s a shared decision-making process when patients and families talk with their doctors about any potential treatment,” Dr Petersen emphasised. “As we discuss the clinical meaningfulness of slowing the Alzheimer’s disease progression, realistic expectations of benefits and risks must be conveyed.”