Today's Reality in Alzheimer's Disease: Timely Detection, Collaborative Care and Real-World Impact

This article is paid and sponsored by Eli Lilly and Company

Jamie is an Alzheimer's disease patient, and Dr. Cara Leahy, DO, is Director for Cognitive Disorders at Memorial Healthcare and practicing doctor of neurology at Memorial Healthcare Institute for Neuroscience. They are paid partners of Eli Lilly and Company.

Key Takeaways

• Timely and accurate Alzheimer’s disease (AD) diagnosis is critical for access to care planning, including potential treatment with disease-modifying therapies.
• Strong patient-provider partnerships can enable timely assessment and treatment.
• AD blood tests are expanding access to help aid in a timely diagnosis.
• Amyloid-targeting therapies (ATTs) can help slow cognitive decline in patients with early symptomatic AD.
• Early intervention and shared decision-making empower patients and can improve real-world outcomes.

The Urgency of Timely and Accurate Alzheimer’s Disease Detection

For Jamie—a 62‑year‑old healthcare quality manager, a wife of 45 years, and a grandmother of 5—an Alzheimer's disease (AD) diagnosis came at a moment when she was ready to begin a new chapter of her life.

"I've worked for 43 years in healthcare, and I want to retire and have fun. That’s what was going through my head. I wasn’t ready for this, and I want to do what I can to continue to do the things that are important to me for as long as I can," Jamie, who was diagnosed with early symptomatic AD, said.

Jamie’s reaction isn't uncommon among the nearly 5 million people over the age of 65 in the US that dementia due to AD affects, and an additional approximate 5 to 7 million living with mild cognitive impairment (MCI) due to AD.¹ Timely detection and intervention have never been more critical.²

Until recently, most available therapies addressed symptoms, but now disease-modifying treatments target the underlying pathology of AD and can slow disease progression in their patients. ³ However, the window for effective intervention is narrow. Patients who progress beyond the early symptomatic stage will miss the opportunity to potentially benefit from amyloid-targeting therapies (ATTs) approved to treat early symptomatic AD in patients in the MCI or mild dementia stage.⁴

“A timely diagnosis matters in Alzheimer's disease,” Jamie’s neurologist, Cara Leahy, DO, director for cognitive disorders at Memorial Healthcare and practicing doctor of neurology at Memorial Healthcare Institute for Neuroscience, said. “Current published data suggests that patients who begin ATTs early have better results.”

The Value of Patient-Physician Partnership

Jamie credits her proactive stance and the trusting, open relationship she built with Dr. Leahy for getting the timely evaluation and testing she needed.

About a year ago, Jamie started noticing she was having a hard time coming up with common words, and found her friends were finishing her sentences. She knew something wasn’t right. She also was very aware of AD, as her aunt, mother, uncle, and sister had previously faced the disease. “If it weren’t for that, I might not have gone to speak with my doctor when I did,” Jamie noted.

She first brought her concerns to her primary care provider (PCP) but wasn’t satisfied with the outcome. “I wasn’t comfortable with just a standard cognitive test. I had a strong suspicion that something was wrong, so I pursued a referral to a neurologist for a more thorough comprehensive evaluation,” Jamie said. She was then connected to Dr. Leahy.

Her experience reflects a common gap: a national claims-based study* showed that most patients with an AD or related diagnosis had no further care conversations beyond the PCP visit, and only ~15% with an AD or related diagnosis had a claim for a specialist visit.⁵ This underscores why engaging PCPs in earlier detection and streamlined referral pathways is critical, and where neurologists can partner to close the gap.

“Dr. Leahy was very positive and informative from the start. First she explained the tests she uses to assess and diagnose the cause of memory and thinking issues. She also explained the use of biomarker testing and the different options, which could include a blood test. I never felt like I wasn’t being heard or that I was alone. I remember she said, ‘We got this, Jamie,’” Jamie explained.

When patients and providers talk openly, it can prompt timely history, physical, and cognitive assessments, relevant lab work, and biomarker testing, which are all critical diagnostic steps for patients like Jamie.⁴

“I am optimistic about what may become possible as AD blood tests become more widely adopted in primary care,” Dr. Leahy said. “They are a key to expanding access to new novel therapies and will also give primary care the necessary information to refer the most appropriate patients for specialized care.”

Early diagnosis, incorporating regular cognitive screenings and biomarker testing via blood, positron emission tomograph (PET) scan, or cerebrospinal fluid (CSF) are crucial to aid in diagnosing AD early and can help with the selection of patients who may be appropriate for disease-modifying therapies (DMTs). The adoption of blood tests is becoming more prevalent given that they are more easily accessible.⁴

Dr. Leahy’s proactive engagement with Jamie serves as a reminder that more effective care planning is often rooted in an early diagnosis, especially given not all patients persistently self-advocate in the way she did. Through strong patient-provider collaboration, care planning becomes tailored, timely, and informed by the latest clinical advances.

Today’s Treatment Landscape

The AD treatment landscape is undergoing a significant shift, moving from only symptomatic treatments available towards also incorporating disease-modifying treatments that target underlying pathology for appropriate patients.³

Recent advances in ATTs have introduced a new era of intervention, where slowing disease progression is now clinically achievable.³ ATTs are designed to reduce amyloid plaques, a hallmark pathology of AD, and are indicated for patients with early symptomatic AD and confirmed amyloid pathology.^3,6

The introduction of ATTs, such as Kisunla® (donanemab-azbt) injection for intravenous use (350 mg/20 mL), which is approved in the US to treat adults with early symptomatic AD, specifically MCI or mild dementia stage of disease and confirmed amyloid pathology marks a paradigm shift to targeting the underlying pathology with the treatment goal of slowing progression of cognitive and functional decline in patients with early symptomatic AD.^6-8

When considering treatment with Kisunla, it is also important to understand that there are some key risks to be aware of. Kisunla, like other amyloid-targeting therapies, carries a Boxed Warning reflecting a higher risk of amyloid-related imaging abnormalities (ARIA) with therapy. ARIA is usually asymptomatic, although serious and life-threatening events can occur. ARIA can be fatal.

Patients treated with this class of medications, including Kisunla, who are ApoE ε4 homozygotes have a higher incidence of ARIA, including symptomatic and serious ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA.

Kisunla can cause hypersensitivity and infusion-related reactions, some of which may be serious and life-threatening. When present, promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy.⁶

Please see additional Important Safety Information below and full Prescribing Information for Kisunla, including Boxed Warning regarding ARIA, and Medication Guide.

Following her diagnosis, Jamie felt supported and informed in her care planning discussions with Dr. Leahy, and described the decision-making process as very collaborative.

“She drew me this diagram and explained the facts about my treatment options, including Kisunla. She gave me the statistics, and I made my decision to start treatment with Kisunla,” Jamie said. “She wanted me to make that decision based on the available information, so I felt empowered and supported.”

“I think out loud when I’m discussing ATTs with a patient,” Dr. Leahy said. “I talk about the aspects of their case that are reassuring and aspects that concern me related to their amyloid-related imaging abnormalities (ARIA) risk. That’s key for me to give that feedback and assess their willingness to accept risk.”

Kisunla® (donanemab-azbt): A Unique Approach to Dosing with ATTs for Early Symptomatic AD

Within the evolving AD treatment landscape, Kisunla is a once-monthly ATT with dosing that allows for patients to complete treatment course. Prescribers can consider completing treatment course based on reduction of amyloid plaques to minimal levels on amyloid PET imaging.⁶

In phase 3 clinical trials, dosing was stopped in response to observed effects on amyloid imaging. Amyloid PET values may increase after treatment with Kisunla is stopped. There are no data beyond the 76-week duration of TRAILBLAZER-ALZ 2 to guide whether additional dosing with Kisunla may be needed for longer-term clinical benefit.⁶

The FDA approved Kisunla in July 2024 based on the pivotal TRAILBLAZER-ALZ 2 (NCT04437511) phase 3 study that assessed disease progression in early symptomatic AD by reducing amyloid plaques. TRAILBLAZER-ALZ 2 had dual primary analysis populations. The study was powered to test the results of Kisunla in the low-medium tau (low tau to medium tau=earlier neuropathology) population,** and also allowed enrollment of high tau participants so Kisunla could be tested in the overall population (the low-medium tau population plus high tau participants).^6,7 The primary endpoint was a change in integrated Alzheimer's Disease Rating Scale (iADRS) score from baseline to 76 weeks (impact on cognitive and function decline) for those with AD with MCI or mild dementia, and confirmed presence of amyloid pathology.⁶

The study demonstrated that Kisunla significantly slowed cognitive and functional decline by the iADRS at 18 months (week 76).⁶ In the low-medium (intermediate) tau population who were less pathologically advanced in their disease, participants treated with Kisunla achieved on average a 35% slowing of decline with an adjusted mean change difference from placebo of 3.3 (P<0.0001). At week 76 (Kisunla: n=418; placebo: n=444), the adjusted mean change from baseline for patients treated with Kisunla was -6.02 versus -9.3 for placebo.^6-8

In the overall study population, data showed that participants treated with Kisunla demonstrated 22% slowing of decline with an adjusted mean change difference from placebo of 2.9 (P<0.0001).^6-8 At week 76 (Kisunla: n=583; placebo: n=653), the adjusted mean change from baseline for patients treated with Kisunla was -10.19 versus -13.11 for placebo.⁶ iADRS scores range from 0 to 144 with lower scores indicating greater cognitive and functional impairment.⁶

In the same overall population (n=1736), Kisunla also reduced risk of progressing*** to the next stage of disease versus placebo by 37% through 76 weeks; P<0.001 (HR=0.63; 95% CI: 0.51, 0.77).⁷

“The data in the pivotal trial of ATTs, including Kisunla, show patients in the early clinical stage of the disease and with low pathologic markers of disease tau were shown to have the greatest slowing of disease on measures of cognition and function,” explained Dr. Leahy. “In my experience, I believe the patients I have treated have declined more slowly when they are started in the MCI stage versus when they start in the mild dementia stage. Similar to most conditions, treating earlier is generally better.”

Jamie found that having in-depth conversations with Dr. Leahy about the possibilities of treatment made a big difference for her. “Dr. Leahy was so informative. She walked through the risks vs benefits of treatment with me. I had clarity during the treatment process, and I remained positive because of the opportunities for infusions with Kisunla and the potential to complete the course of treatment.”

Patient Perspective and Real-World Experience on Kisunla

Jamie’s story is a testament to the power of building trusted relationships with patients and thoughtful education throughout the care journey, offering a unique perspective as someone who has worked in healthcare and is now living with AD, exemplifying the real-world benefits of early detection, shared care planning, and what timely ATT initiation can look like.

“I’ve had 9 infusions now. So far, I’m handling the infusions well. I am closely monitored by the nursing staff, ensuring that I continue to feel well throughout my infusion and post-infusion observation time,” Jaime said. “I tell my friends it’s important to have early discussions with their doctors at the first signs of memory and thinking issues, given the availability of effective treatments and the potential to miss the treatment window opportunity and benefit from intervention. Don’t sit around for 2 or 3 years–go now so you can have more care planning options.”

Dr. Leahy and Jamie’s integrated disease management journey demonstrates how collaborative care, timely diagnosis, and patient empowerment can transform the real-world impact of AD.

“Every appointment is an opportunity to talk through options, answer questions, and make sure patients feel supported in the decisions ahead,” Dr. Leahy said. “That ongoing dialogue is how we build trust and ensure patients feel confident in their care.”

To learn more about Kisunla and access resources, visit Kisunla.Lilly.com/HCP.

Lilly is committed to supporting patients, providers, and infusion centers in navigating the Medicare reimbursement landscape. To learn more about available coverage with evidence development studies, how to enroll patients in these studies, and requirements for Medicare reimbursement, please visit kisunla.lilly.com/hcp/support-resources or call Lilly Support Services^TM at 1-800-LillyRx (1-800-545- 5979).

IMPORTANT SAFETY INFORMATION FOR Kisunla® (donanemab-azbt)

Kisunla is contraindicated in patients with known serious hypersensitivity to donanemab-azbt or to any of the excipients. Reactions have included anaphylaxis.

Amyloid-Related Imaging Abnormalities (ARIA)

ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, can occur. ARIA can be fatal. When present, reported symptoms associated with ARIA may include, but are not limited to, headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time.

In Study 1, safety was assessed in patients who received Kisunla Dosing Regimen 1 (n=853) compared to those who received placebo (n=874). In Study 2, the effect of different dosing regimens of Kisunla on ARIA was assessed, including in patients who received Kisunla Dosing Regimen 2 (n=212).

Incidence of ARIA

A lower incidence of ARIA was observed with Dosing Regimen 2 as compared to Dosing Regimen 1. Therefore, Dosing Regimen 2 is the recommended dosage for Kisunla.

In Study 1, symptomatic ARIA-E occurred in 6% of patients through 18 months of treatment with Kisunla.

Clinical symptoms associated with ARIA resolved in approximately 85% of those patients.

Including asymptomatic radiographic events, ARIA, ARIA-E, and ARIA-H were observed with Kisunla: 36%, 24%, and 31% of patients treated with Kisunla, respectively compared to 14%, 2%, and 13% of patients on placebo. There was no increase in isolated ARIA-H for Kisunla vs placebo.

In Study 2, symptomatic ARIA-E occurred in 3% of patients and symptomatic ARIA-H occurred in less than 1% of patients through 12 months of treatment with Kisunla. Clinical symptoms associated with ARIA-E resolved in approximately 67% of patients at 12 months. Including asymptomatic radiographic events, ARIA, ARIA-E, and ARIA-H were observed in 29%, 16%, and 25% of patients treated with Kisunla.

Incidence of Intracerebral Hemorrhage (ICH)

ICH >1 cm in diameter was reported in 0.5% of patients treated with Kisunla vs 0.2% on placebo in Study 1 and in 1% of patients treated with Kisunla in Study 2. Fatal events of ICH have been observed in patients taking Kisunla.

Risk Factors for ARIA and ICH

ApoE ε4 Carrier Status

The risk of ARIA, including symptomatic and serious ARIA, is increased in ApoE ε4 homozygotes.

Recommendations for management of ARIA do not differ based on ApoE ε4 carrier status. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. An FDA-authorized test for detection of ApoE ε4 alleles is not currently available. Currently available tests may vary in accuracy and design.

Radiographic Findings of Cerebral Amyloid Angiopathy (CAA)

Neuroimaging findings that may indicate CAA include evidence of prior ICH, cerebral microhemorrhage, and cortical superficial siderosis. CAA has an increased risk for ICH. The presence of an ApoE ε4 allele is also associated with CAA.

The baseline presence of at least 2 microhemorrhages or the presence of at least 1 area of superficial siderosis on magnetic resonance imaging (MRI), which may be suggestive of CAA, were identified as risk factors for ARIA. Patients were excluded from enrollment in Study 1 and Study 2 for findings on neuroimaging of prior ICH >1 cm in diameter, >4 microhemorrhages, >1 area of superficial siderosis, severe white matter disease, and vasogenic edema.

Concomitant Antithrombotic or Thrombolytic Medication

In Study 1, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed. The majority of exposures to antithrombotic medications were to aspirin. The number of events and the limited exposure to non-aspirin antithrombotic medications limit definitive conclusions about the risk of ARIA or ICH in patients taking antithrombotic medications.

One fatal ICH occurred in a patient taking Kisunla in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent in Study 1, and one fatal intracerebral hemorrhage occurred in the setting of ARIA and the use of a thrombolytic agent in Study 2. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E, and additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (eg, tissue plasminogen activator) to a patient being treated with Kisunla. Advise patients to carry information that they are being treated with Kisunla.

Caution should be exercised when considering the use of Kisunla in patients with factors that indicate an increased risk for ICH and in particular for patients who need to be on anticoagulant therapy or patients with findings on MRI that are suggestive of CAA.

Monitoring and Dose Management Guidelines

Obtain a recent baseline brain MRI prior to initiating treatment and prior to the 2nd, 3rd, 4th, and 7th infusions. Enhanced clinical vigilance for ARIA is recommended during the first 24 weeks of treatment with Kisunla. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.

Recommendations for dosing in patients with ARIA-E and ARIA-H depend on clinical symptoms and radiographic severity. Depending on ARIA severity, use clinical judgment in considering whether to continue dosing, interrupt treatment, or permanently discontinue Kisunla. See Prescribing Information for additional dosing considerations.

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients who were treated with Kisunla. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy.

Infusion-Related Reactions (IRR)

IRRs were observed with Kisunla with the majority occurring within the first 4 infusions. Most IRRs occurred during the infusion or within 30 minutes after completion of the infusion, however some have occurred hours after an infusion. Signs and symptoms of IRRs include chills, erythema, nausea/vomiting, flushing, difficulty breathing/dyspnea, sweating, elevated blood pressure, headache, chest pain, and low blood pressure.

In the event of an IRR, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Consider pre-treatment with antihistamines, acetaminophen, or corticosteroids prior to subsequent dosing.

Adverse Reactions: The most common adverse reactions reported in ≥5% of patients treated with Kisunla and ≥2% higher than placebo were ARIA-H microhemorrhage, ARIA-E, ARIA-H superficial siderosis, headache, and IRRs.

Kisunla (donanemab-azbt) injection for intravenous use is available as a 350 mg/20 mL single-dose vial.

Please see full Prescribing Information, including Boxed Warning regarding ARIA, and Medication Guide.

DN HCP ISI 01JUL2025

*The analysis commissioned by Lilly was completed using IQVIA ELAAD (Enterprise Longitudinal Access and Adjudication Data) Medical Claims from approximately 6.5 million patients who received AD, dementia or related diagnoses from January 2021-December 2024. This analysis represented a subset of overall patients and should not be assumed to represent the totality of patients diagnosed. The analysis period includes time when approved amyloid-targeting therapies were not yet available, which may have limited observed initiation. Claims data predated: retirement of Medicare amyloid PET National Coverage Determination which impacted access by requiring scans to be performed under Coverage with Evidence Development; widespread availability and significant Medicare coverage of disease-modifying therapies; and significant insurance coverage for biomarker diagnostic testing.⁵

**There were 2 primary analysis populations based on tau PET imaging with flortaucipir: 1) low-medium tau level population (SUVR of ≥1.10 and ≤1.46), and 2) combined population of low-medium plus high tau (SUVR >1.46).⁶

***Progression to next clinical stage was defined as any increase in Clinical Dementia Rating Scale-Global Score (CDR-GS) at 2 consecutive visits from baseline. 0=normal; 0.5=very mild dementia; 1=mild dementia; 2=moderate dementia; 3=severe dementia.The HR is the relative risk reduction for substantial decline achieved by Kisunla vs placebo.⁷

References

1. Alzheimer’s Association. 2025 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 21, 5 (2025): 66-117.
2. Potashman M, et al. Estimating Progression Rates Across the Spectrum of Alzheimer’s Disease for Amyloid-Positive Individuals Using National Alzheimer’s Coordinating Center Data. Neurol Ther. 2021;10(2):941-953.
3. Wessels AM, Dennehy EB, Dowsett SA, et al. Meaningful clinical changes in Alzheimer disease measured with the iADRS and illustrated using the donanemab TRAILBLAZER-ALZ study findings. Neurol Clin Pract. 2023;13(2):e200127. doi:10.1212/CPJ.0000000000200127
4. Porsteinsson AP, Isaacson RS, Knox S, et al. Diagnosis of early Alzheimer’s disease: clinical practice in 2021. J Prev Alzheimers Dis. 2021;3(8):371-386.
5. Unlocking Timely Access to Alzheimer’s Disease Detection and Diagnosis. Lilly USA, LLC. July 13, 2025. Accessed November 25, 2025. https://www.lilly.com/news/stories/alzheimers-detection-and- diagnosis.
6. Kisunla (donanemab-azbt). Prescribing Information. Lilly USA, LLC.
7. Sims JR, Zimmer JA, Evans CD, et al.; TRAILBLAZER-ALZ 2 Investigators. Supplement 1: I5T-MC-AACI clinical study protocols. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512-527. doi:10.1001/jama.2023.13239
8. Data on File. Lilly USA, LLC. DOF-DN-US-0053.

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