Approach shifts in treating Alzheimer’s disease
Alzheimer’s disease treatment has undergone a significant transformation in recent years, experts say.
A shift from symptom management and supportive care to the introduction of disease-modifying therapies marks a pivotal change in how medical professionals approach the disease.
These new treatments target the underlying pathology of Alzheimer’s, offering the potential to slow cognitive decline rather than merely alleviating the symptoms.
One of the most promising approaches involves administering lecanemab and donanemab monoclonal antibody treatments that target amyloid beta plaques in the brain believed to play a key role in the progression of Alzheimer’s. Both treatments work by binding to and removing amyloid beta proteins from the brain. These proteins accumulate and form plaques — the hallmark of Alzheimer’s disease. The treatments aim to slow the progression of cognitive decline by reducing these plaques.
Dr. Nikita Urval, a neurologist with Independence Health System, said it is difficult to compare the effectiveness of the two infusion treatments because they were not studied in the same clinical trial.
“Based on the reported outcomes from the clinical trials, donanemab had a slowing of decline up to 35% compared to placebo, and lecanemab had a 27% slower cognitive decline at 18 months compared to placebo,” she said.
Doctors follow several steps to determine if a patient is a candidate for the treatments, Urval said. “We need to get a full medical history, as there are many other conditions that could be contributing to cognitive changes other than Alzheimer’s disease.”
They also conduct cognitive screenings to determine the extent of memory changes.
“An MRI of the brain is required to see if there is any structural cause for memory changes and to see if there has been any prior bleeding in the brain, which could put someone at risk for bleeding with the infusion therapy,” she said.
The most-important step, she said, is to verify the presence of any amyloid in the brain. A PET scan can detect amyloid in the brain or a lumbar puncture to evaluate for its presence in the fluid surrounding the brain. A third option — a blood test for amyloid presence — is not yet accepted by insurance companies.
Once patients are approved for treatment, Urval said it’s up to them which method to use.
“There are pros and cons to both medications,” she said. “I try to educate my patients as much as possible about the different treatments, but ultimately, it is up to them which one they would prefer to move forward with.”
Amyloid-related imaging abnormalities, or ARIA, are a potential side effect of these treatments. ARIA is a change in the brain that doctors can see on MRI scans after patients receive lecanemab and donanemab infusions. It causes brain swelling or tiny brain bleeds. Symptoms can include confusion, dizziness, headaches, nausea, seizures, vision changes and difficulty walking.
Doctors monitor for ARIA using MRIs. For lecanemab, Urval said three MRIs are performed after starting infusion treatment — before the fifth, seventh and 14th infusions. For donanemab, patients receive four MRIs before the second, third, fourth and seventh infusions.
ARIA treatment varies depending on whether the patient is symptomatic. If abnormalities are found during MRIs without symptoms, clinicians will determine whether infusion treatment can be continued, needs to be temporarily paused, or permanently stopped.
“If someone is having symptoms, we are more likely to also give steroids to help, and we are more likely to either temporarily or permanently stop the infusion treatment,” Urval said.
Some preexisting conditions can make patients more susceptible to ARIA, including carrying the APOE4 gene associated with an increased risk of developing Alzheimer’s. Prior brain bleeds or vascular abnormalities such as an aneurysm boost the chances of ARIA.
“Additionally, if someone is taking blood thinners or anticoagulants, they would be at higher risk for ARIA,” Urval said. “None of these conditions specifically prevent you from being able to get the infusion therapy, but it is something to consider when discussing the possibility of side effects.”
While these infusion treatments are groundbreaking, one local organization continues to fund the discovery of breakthrough drugs and novel treatments to eliminate all types of dementia.
The Clear Thoughts Foundation Consortium was formed in 2010 with this goal in mind. It’s composed of top researchers and doctors from the University of Pittsburgh and UPMC and garners collaboration among renowned researchers to accelerate advancements to expedite the elimination of dementia.
Executive director Cait Fenello said the consortium’s approach differs from traditional research models, which typically follow a one-to-one approach. The consortium distributes one grant among multiple researchers who share the funding, project hypotheses, methodologies and outcomes.
“This collaborative framework fosters teamwork across various projects, utilizing shared lab equipment, animal testing models, and research findings,” she said. “As a result, resources — time, money expertise — are optimized, resulting in quicker discoveries at a lower funding threshold.”
Two of the most promising areas of research the consortium is exploring include melatonin and therapeutic plasma exchange. The consortium believes melatonin, a natural sleep hormone, may help protect the brain from damage that leads to dementia. While melatonin is available over the counter, researchers don’t know much about its safety or efficacy for dementia prevention.
“CTF Consortium’s ongoing research, utilizing mouse tissue both with and without melatonin treatment, aims to assess efficacy, gender differences, optimal dosage and treatment duration,” Fenello said.
Therapeutic Plasma Exchange is being investigated as a potential treatment to slow the progression of Alzheimer’s disease. Fenello said a previous human clinical trial demonstrated that it was effective for some participants, but the mechanisms behind this effect and its impact on preserving vascular function are still not fully understood.
While science continues to advance, family caregivers still can receive the help they need through local support groups. One such program — Caring for the Caregivers — meets at 6 p.m. on the second Thursday of each month at the South Butler Community Library. It provides a safe space for caregivers to share their experiences and challenges.
Cabot resident Michelle Govan was inspired to start the group after realizing there was a need in her community. She is a registered nurse and certified dementia practitioner. Dementia family caregivers face multiple challenges and can feel isolated and unprepared, Govan said. The group’s goals are to remove that secluded feeling and replace it with newfound confidence through problem-solving.
“My hope is that when the participants know and trust each other, there’s a bond that’s created and they become supports for each other outside of the monthly meeting,” Govan said.
This article first appeared in the November edition of Butler County Business Matters.
