Elevating the Role of Advanced Practice Providers in the Evolving Alzheimer Disease Landscape

Alzheimer disease presents one of the greatest clinical and public health challenges of our time, with a growing patient population, rising economic burden, and novel treatment options reshaping the care landscape. In a recent Peer Exchange from The American Journal of Managed Care®, panelists discussed how advanced practice providers (APPs) are driving transformation in Alzheimer disease management through early detection, personalized treatment, and comprehensive support for patients and caregivers. They highlighted the growing leadership of APPs in multidisciplinary collaboration, operational efficiency, and equitable access to care. The session was moderated by Ken Cohen, MD, FACP, executive director of translational research for Optum Health.

Burden of Alzheimer Disease and the Role of Advanced Practice Providers

Alzheimer disease (AD) is the most common neurodegenerative disease, accounting for 60% to 80% of dementia cases worldwide.^1,2 The number of people with dementia is expected to rise from 57 million globally in 2019 to 152 million cases in 2050.³ The rise is associated with the growth of the elderly population, requiring careful monitoring by health care providers.⁴ Global costs associated with dementia were $818 billion in 2018 and are expected to increase to $2 trillion by 2030, with the largest costs associated with severe stages of disease.⁴

AD is characterized by cognitive and functional decline, most notably progressive short- and long-term memory loss.¹ The hallmark of AD pathology is the extracellular deposition of amyloid β (Aβ) and formation of intraneuronal neurofibrillary tangles of hyperphosphorylated tau. Initially, the Aβ deposition is asymptomatic, but over time cortical accumulation results in inflammation, tauopathy, and neurodegeneration.¹ Newer AD treatments that target Aβ are therefore expected to be most effective at preventing degeneration when started early in the disease course.¹

The symptoms of AD severely impact daily living, compromising independence and placing a significant burden on caregivers.¹ The growing prevalence and demands of AD have increased the need for specialized services and multidisciplinary care coordination.² A broad network of stakeholders, including primary care physicians, APPs, geriatricians, neurologists, radiologists, psychiatrists, psychologists, therapists, social workers, and people in the community, must collaborate to meet the challenges of AD management.²

To relieve the strain on specialist practices and primary care providers, there is an increased role for APPs, including physician assistants (PAs) and nurse practitioners (NPs), in the care of AD patients.² Although the absolute number of APPs has increased in recent years, there is limited specialization of APPs in caring for elderly people.² In 2018, just 0.8% of PAs were certified in geriatric care, and 46% of those worked in extended care facilities or nursing homes.⁵ Among more than 385,000 NPs licensed in the United States in 2022, 0.8% had a certification in gerontology, 5.3% had a certification in gerontology acute care, and 8.8% had a certification in gerontology primary care.⁶ Success depends on communication among these parties, ensuring timely diagnosis, consistent follow-up, and alignment on treatment objectives and patient education.

Stakeholder Insights

Barbara Joy Snider, MD, PhD, a neurologist at Washington University School of Medicine in St Louis, Missouri, discussed the increased burden of AD and the implications for care delivery. “The number of patients we’re seeing with [AD] is increasing with the baby boom. And as we get new treatments…we need to see even more patients because we need to see people when the disease is mild. There are also the financial implications today, the cost of [AD] treatment specifically, and care for people.… This is a disease we need to get our heads around, we need to find treatments for, or else our health care system will be in a very bad way in the not-too-distant future.”

Kavita Nair, PhD, FAAN, a professor in the Department of Neurology and Center for Pharmaceutical Outcomes Research at the University of Colorado Anschutz Medical Campus in Aurora, Colorado, said key stakeholders involved in Alzheimer care have changed. “Previously it was primarily a decision between a patient and their neurology or geriatrician prescriber. But in providing care with anti-amyloid therapies, there’s an entire care continuum and a whole new set of stakeholders.… As patients show up at the emergency room, neurocritical care/neurologists and care providers are appropriately informed as to what not to give these patients who are at risk for different kinds of complications. Pharmacy is a very critical provider as well in order to make sure that protocols flow well [in] terms of getting infusions[too].” She said primary care is becoming an increasingly important partner because of the need for early diagnosis and treatment. “The continuum of stakeholders is increasing, and it creates opportunities, but also creates some complexity in health care systems and community settings as well.”

She said the decision to potentially start anti-amyloid treatment requires several visits, including reviewing diagnostic criteria and testing. “The APP…is in a critical and in an excellent position to be that facilitator in having those conversations, explaining the risk-benefit profile, and being centrally involved in triaging.… They’re a critical function for patients in this population who might be considering or eligible for anti-amyloid therapy.

Jordan Mast, MMS, PA-C, a physician assistant at the Colorado Neurological Clinic in Denver, Colorado, agreed on the involvement of neurology APPs. “We were being asked to evaluate these patients for a cognitive impairment disorder, and they’re seeing us primarily and we become very, very comfortable at having this conversation.”

Mast highlighted the importance of education. “I’ve been very active with the AAPA, the American Academy of Physician [Associates] group, in educating my colleagues on neurology.… I think in our board exams, about 5% or 6% is neurology specific, so the experience and understanding of neurology for new providers that are coming out of school is very limited.… The more education that’s out there, the more comfort level we have with seeing these patients on a regular basis.”

Stefanie Eymar, MSN, FNP, a nurse practitioner at the Colorado Neurological Clinic, added that whether patients are seen first by the physician or the APP depends on the level of experience. Experienced APPs “complete the initial consults [and] we also perform and order the initial testing as well as counsel the family.… We are involved in the care with the patient from the beginning through the end or start of therapies.”

Mast agreed. “We’ve been in practice over 10 years.… I feel like we have a very good bedside manner and patients really gravitate toward that relationship.”

Snider shared her experience at a large academic medical center. “We do not have our APPs see new patients, except with rare exceptions, which is a problem. And I think it’s important to move more toward that. But academia has a little less comfort with it.” She believes APPs are often more experienced than our clinicians “because our clinicians are academics, and we’re only part time in the clinic. So particularly as with these new drugs…we want to get people when they’re really mild [and don’t want them to] spend 6 to 9 months waiting for an appointment with me.”

Nair agreed that academia needs to step up. “At the University of Colorado…our behavioral group has just hired their first APP.” She highlighted the unmet need in the number of people being examined. “Our wait times just for our behavioral clinic are 8 months out. We don’t see self-referrals and we don’t see worried [well patients]. This is a disease that doesn’t wait.… There’s been sort of a reluctance to invest resources in this area…the primary reimburser is Medicare, and it’s not seen as much of a moneymaker as in some of the other neurology subspecialties as [multiple sclerosis] or some of the newer neuromuscular areas.”

Mast referred to research into asymptomatic AD. “If we have data to suggest that we could treat [AD] before they start to develop symptoms, how inundated are we going to be[with] patients self-referring or having a family history of [AD] that are scared about that potential?… Talking to new PA students about the excitement of neurology, trying to get them in because obviously it takes a lot longer to train MDs and DOs, so PAs can, and nurse practitioners can get into the field much more quickly, be trained on the spot, and help to stymie that a little bit. It’s exciting, but also very terrifying.”

Strategies for Early Identification

Due to the progressive nature of the disease, timely and accurate identification and diagnosis of AD is key.² Reporting of cognitive, behavioral, or functional changes by the patient, care partner, or clinician should lead to a multitiered evaluation by the clinician. This includes establishing goals and processes through patient-centered communication and shared decision-making, history of present illness, structured multidomain systems review, and information on individualized risk factors.⁷ Clinicians should perform a validated mental status examination that assesses cognition, mood, and behavior, and a dementia-focused neurologic examination.⁷ Validated cognitive assessment instruments include the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Mini-Cog, and General Practitioner Assessment of Cognition, among others.⁸

In vivo confirmation of AD pathology is essential for accurate diagnosis. Traditional clinical biomarker tests used to confirm AD pathology in vivo use PET with radiotracers that bind to amyloid plaques or insoluble tau aggregates, or cerebrospinal fluid assays that measure Aβ42, Aβ40, total tau, and phosphorylated tau (p-tau).⁹ Although these tests are highly accurate, they are considered invasive and issues exist around cost and access.⁹

Blood-based biomarkers for AD have been developed as a lower cost and are a less invasive option, measuring plasma p-tau and Aβ markers, which are compared with reference standard tests in individuals with mild cognitive impairment or dementia.⁹ In a systematic review of 31 blood-based biomarkers, diagnostic test accuracy varied significantly with pooled sensitivity ranging from 49% to 91% and pooled specificity ranging from 62% to 97%.⁹ The study concluded that test results should be interpreted in the context of the specific test used and integrated within a comprehensive clinical assessment.⁹

Two amyloid plaque–lowering monoclonal antibodies have been approved for the treatment of early-stage AD: lecanemab in 2023 and donanemab in 2024, based on their ability to slow clinical disease progression in phase 3 clinical trials.^7,10-12 The availability of these disease-modifying therapies increases the need for timely detection, accurate diagnosis, and appropriate treatment options for early AD in a collaborative health care system.⁷

Structural MRI of the brain can be used early in the assessment to evaluate patient eligibility for anti-amyloid immunotherapy and monitoring while on treatment.¹³ Treatment with anti-amyloid immunotherapy has been associated with radiographic findings resembling cerebral amyloid angiopathy-related inflammation, termed amyloid-related imaging abnormality (ARIA).¹³ ARIA occurred in approximately 10% to 30% of all participants treated in clinical trials of aducanumab, lecanemab, and donanemab.¹³ Genetic analysis can inform on ARIA risk because apolipoprotein E4 (APOE4) genotype carrier status is associated with elevated vascular amyloid deposition, increasing the risk of cerebral amyloid angiopathy.^7,13

Stakeholder Insights

Lara Kroepsch, PA-C, a physician assistant at Roaring Fork Neurology in Basalt, Colorado, said early detection is key and more likely to happen in the primary care office. “I think what we need to start doing a better job of is talking to our patients. I feel like cognitive health kind of gets glossed over when a patient’s coming in for their annual wellness visit, but it needs to be a focus, especially now as we’re trying to find and work toward earlier detection.… We should be doing a simple MMSE or a MoCA at least once a year with an annual wellness visit, again, baseline information that’s going to help with early detection, and really kind of treating cognitive screening like we are other preventive screening tools.”

Snider added, “I would also advocate for talking more to someone else who knows the patient well, because while some patients detect things early, some don’t, and so tools like the AD8 and other things you give to a care partner can be really helpful at triggering that early detection.”

Mast agreed that there is a need for cognitive screening. “I always joke with my patients that I think, I hope, in the future, you hit 45, it’s time for your colonoscopy; and then you hit 55, it’s time for your blood-based biomarkers. Hopefully the future of Alzheimer disease diagnosis will be blood testing, and we’re getting closer and closer to that.”

“Optum Health, which cares for 23 million patients nationwide and is the largest of the ambulatory delivery systems in the country, has just launched a prospective screening program,” Cohen said. “So now all of our 65-year-olds at their annual wellness exam will receive an MMSE or a Mini-Cog.… It’ll be interesting to see how this prospective national screening program actually plays out.”

Because of new disease-modifying therapies, the timing becomes very critical, said Snider. “We know that these therapies are effective at the very mild to mild stage…so we need to work really hard to identify people early.” She warned that “sometimes [with] the MMSE, the MoCA, the [Saint Louis University Mental Status examination], I have patients on treatment who clearly have impairment who still have a perfect score. It really depends on educational level, attainment, how good you are at taking these tests. Having some sort of screening to identify people where the family has noticed impairment is going to be critical.”

“When people would come in with cognitive impairment, if it was mild enough, we would just kind of watch and wait,” Mast said. He added that its normal for people to blame things like normal aging, stress, lack of sleep. “Certainly, those are important factors, but we’re really getting more and more sensitive to the potential that these cognitive impairment symptoms are atypical for them.”

Eymar agreed that there can be difficulties with patient acceptance. “When we have these tools to give them further assessments or to actually give them a diagnosis, there is a hesitancy or a fear of, ‘If I see these tests, if I see these results, what are the implications?’ ”

Snider said that the concern is that “particularly with the blood-based biomarkers, which are great…right now, we don’t want to test everybody. We don’t want to test those presymptomatic people, so teaching our primary care docs to take at least a 30-second or 2-minute dementia history is going to be critical in that.” Cohen pointed to data showing that more than two-thirds of those patients have severe anxiety associated with positivity. “I think we need to think carefully about how we integrate that into our treatment efforts,” he said.

Mast highlighted the significance of champions in this area. “One of the things I think can be incredibly helpful and something that when we bring on new APPs, I always like to tell them, ‘Look, you can become an expert in an area. You can go to conferences. You can talk to experts. It takes time, but if you have a passion in[AD], then train yourself [with our help].’ ”

Operational Challenges with Early Identification

“We were actually almost kind of inundated with a lot of referrals from primary care physicians that we work with in the community,” said Eymar. “Several operational challenges that we had initially is the timing of testing. We really had to kind of create an algorithm for what works for our office—which biomarkers, MRI imaging…making sure that we get all the appropriate testing done in an amount of time that doesn’t waste a lot of back-and forth time for the patients because we do have some that travel from far away,…streamlining diagnosis.”

Mast added: “I remember when we started to develop our program, we basically had a meeting among the providers saying, OK, what we do on visit 1, what we do on visit 2, what do we talk about at these visits? How long are the appointments?… We’re kind of writing the script as we go.”

Kroepsch discussed the impact in a rural environment. “We’ve tried to institute as much as we can in-house for our care management, because referring to outside places takes a lot of time, literally driving and waiting. We’re relying heavily on newer blood-based biomarkers for stratifying risk for our patients, and we perform that in-house day of visit oftentimes if the patient seems to be an appropriate candidate. The closest [PET] scanning options are 3 hours away.… And we have an infusion suite in our practice so that we can bring our patients to us and keep them there.… It’s being really selective about what tools provide the most value to the patient and the practice.”

Engaging Caregivers

“PAs and nurse practitioners have, in some cases, a lot more time that they can spend with the patients.” said Mast. “I like to establish a very, very firm foundation that first visit and spend an extensive amount of time educating the families, educating the caregivers, explaining what the word dementia means.… Speaking with them extensively, educating them and developing that initial rapport, I think is incredibly important.… We also are in process of developing a program where we can start to utilize social workers to interact with patients on a regular basis, because I feel like most of us in the panel know this already, but 75% to 90% of the appointments with Alzheimer patients are social conversations.”

Snider pointed to the extra hours on non–patient-facing time that APPs are often asked to do. “That’s a very good point,” said Eymar. “I have a number of patients who are on amyloid-modifying therapies. And I kind of personally want to be involved in every step of that because I feel if something goes awry or there’s [an adverse] effect, at least I know that they didn’t miss an MRI or a follow-up appointment.” She explained that they work with Excel spreadsheets and check all the steps. “MRI? Done. Follow-up visit? Done. Here’s where they’re getting their infusions. Are we getting their infusion notes? It is very, very time-consuming.”

Clinical Considerations in Alzheimer Disease and Treatment Options

Treatment of AD prioritizes addressing social, somatic, and behavioral problems before targeting cognitive symptoms.¹⁴ Behavioral and psychological symptoms of dementia—including agitation, apathy, aggression, delusions, depression, anxiety, and insomnia—can be alleviated through pharmacological and nonpharmacological strategies.¹⁴ Nonpharmacological treatments include personalized activities, enjoyable exercise, and the removal of stressors that trigger behaviors.¹⁴ Pharmacological interventions include selective serotonin reuptake inhibitors (SSRIs) and antipsychotics, although best-practice guidelines encourage limited and judicious use of antipsychotics in AD.¹⁴

Before the development of anti-Aβ monoclonal antibodies, symptomatic treatment of cognitive impairment in AD consisted of acetylcholinesterase inhibitors, including donepezil, galantamine, and rivastigmine.¹⁴ These treatments are FDA-approved for mild to severe AD, but their cognitive and functional benefits as measured by tests of global cognition (eg, MMSE) have been limited.¹⁴

The efficacy of anti-Aβ monoclonal antibodies in slowing decline support the validity of the amyloid cascade as a pathway to cognitive impairment in AD.¹⁴ Key considerations for treatment with these antibodies include confirming early AD-related cognitive impairment and assessing contraindications or conditions that affect the treatment’s risk-benefit balance with a need for regular infusions, MRI monitoring, and risk of adverse effects.¹⁴ The current (initial) administration regimen for anti-amyloid antibodies is via intravenous infusion every 2 to 4 weeks, requiring doctor visits.^12,14 A subcutaneous injectable formulation of lecanemab for once-weekly maintenance dosing has recently become available.¹⁵

Stakeholder Insights

Snider discussed therapeutic decision-making. “It’s tough. We have 1 antipsychotic that’s approved for Alzheimer patients.… We use antipsychotics pretty much as a last resort. And we do have social workers who work with us…having families educated on how to modify behaviors, how to adjust to behaviors.… Our first line is SSRIs, but those take a long time to work.… In geriatrics we start low, go slow but we have family members. They need to care for the patient.… We address behavior first, then SSRIs, then antipsychotics.… We have to talk about the [adverse] effects. But we’re up against a rock and a hard place as far as what to use.”

About newer anti-amyloid therapies, Snider said: “We’ve had APPs for 15 years in large part to help us follow up on our patients.… [Our APPs] have now initiated all the treatment on the 400-plus patients we have on these therapies.… They are the most experienced people in the country treating people with these drugs. And they’re backed up by our physician providers. And all of us have experience…but the APPs are really the front line.”

“It is a time-intensive effort,” added Nair. “It all gets down to the clinical history, the history from the family member and the patient.…We look for people with those very mild changes consistent over time, consistent with [AD]. We certainly look at the sleep, the depression, other causes of dementia, but if somebody looks like they have an odd picture, we would get a brain MRI.… And then we refer them to our amyloid therapy clinic and our APPs, make sure that they’ve had the amyloid testing, they’ve got the APOE testing done.”

On the availability of a subcutaneous version of lecanemab, Eymar was “not quite sure how we’re going to incorporate that because, yes, it’s convenient, but are patients going to do it correctly to remain on schedule? Will we lose them to follow-up because they’re just doing these injections themselves?” She added that for initiation of therapy, “we really still want to stick with intravenous. The initial first few months, the first 6 months ARIA rates are the highest.… We can make sure they’re doing the injections correctly on time. Once it gets to the 18-month mark with lecanemab, then potentially we can transition them to maintenance therapy of the injections. Many of these patients need a social outlet.”

Kroepsch said it can be an expensive social visit in rural areas. “We’re coming at it from the patient side of things, but we also have to be cognizant of that side of things, for sure.… In an ideal situation we’d be able to use injectable options for initiation in addition to continuation in a rural setting where it is difficult. [But] even just the ability to do a once-a-month treatment will feel somewhat liberating and make things a little easier for our patients,” Kroepsch added.

“A big part of it is figuring out how much it’s going to cost them out of pocket,” said Snider. “It’s much cheaper from a medical standpoint not to do an infusion. But how it ends up for the patient is a really good question.… Medicare Part B covers the infusions while Part D covers the injectables. And people’s co-pay may end up being much higher depending on their plan.”

Regarding the evidence required to make treatment decisions, Kroepsch said: “I think a combination, to be honest. I think we try to have an evidence-based practice. We really follow closely with current scientific literature position papers, clinical trial data to make informed decisions.… We’ve been able to participate in a couple of the Alzheimer research studies firsthand.… We’ve also seen medication effect, [we] felt like we hit the ground running when these medicines became FDA approved.”

Mast said they had streamlined the process from diagnosis to anti-amyloid treatment initiation. “I think we’re, in our practice, very aggressive…at getting patients on treatment as early as possible.… Our job is a lot easier, unfortunately, than our primary care colleagues’ because the patients are being referred to us for cognitive impairment.… They’re sending us cognitive screening tools. They’re sending us patients with MRIs already. In some cases, they have blood-based biomarkers completed. Some cases they have amyloid PET scans completed.”

Eymar added, “I would say the longest [time from diagnosis to initiation] would probably be 6 months.”

Snider said their APPs are “extremely involved” in the treatment after ARIA. “The first thing in seeing ARIA is to have excellent neuroradiologist and do excellent MRI scans. We’re very fortunate to be at a major institution [that] made sure that all the hospitals in our system understand what scans they’re supposed to do, understand they have to do heme-sensitive sequences.… I think the reassuring thing from our [real-world study] paper and our continued experience is that the rate of symptomatic ARIA is really very similar to what was seen in the clinical trials.”

Of shared decision-making, Eymar said, “I think that starts at probably the very beginning visit, which is with the patient and with their family. It’s kind of just going with setting expectations for a couple of things. One, it’s how much of a commitment to therapy this is—the scheduling, the time, the number of MRIs—and whether they’re willing to commit to that. And then I’ve had to kind of start saying at the beginning, just really reinforcing this is a progression. We’re trying to slow the progression.… We use a visual tool that I think is very helpful. It shows the trajectory of a patient not on therapy getting worse, and the trajectory of a patient on therapy getting worse at a slightly reduced rate.”

“Delay in diagnosis is probably the biggest barrier that we run into,” said Mast. “Educating our primary care colleagues, educating our patients.… Obviously the most important reason that that’s an issue is that ‘time is brain.’… We need to remove this amyloid to help prevent brain loss or brain matter loss, toxicity to the brain.… Educational sessions like this, going into primary care offices, doing large programs where we can educate our primary care colleagues, PAs, nurse practitioners, physicians on these new therapies.”

Kroepsch said that due to her practice’s unique mountainous location, she makes “a lot of phone calls” and added that “there’s no doubt that some of the most time-intensive work is behind the scenes, navigating health insurance and private insurance, Medicare. We have to be those advocates [for patients].”

Regarding best practices, Eymar said, “I think [there are probably 2] major areas. One is educating yourself, so staying up on the latest treatment regimens, medications. Probably becoming a subspecialist, for example, in [AD] would be a good suggestion for best practices for providers that are giving this care. Secondly, I think it would be to be very open, keeping the lines of communication open, so being able to reach out to that primary care provider in regard to a patient, calling your neuroradiologist to discuss imaging studies.”

“I think one of the consistent themes—and it has gotten better with health care systems—is to get out of the mindset of this is an area or a disease that doesn’t require resources,” said Nair. “Without APPs, we are not going to be able to tackle the problem.… It’s recognizing that this is a field that is growing, it’s exciting, we need resources dedicated out there. It’s not necessarily going to be money-making, but it’s the right thing to do.”

Snider agreed. “I’ve been in Alzheimer research for 30 years, and it’s super exciting to now have disease-modifying treatments. They are only the beginning.” •

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