Donanemab (marketed as Kisunla) is approved for people in the early symptomatic stages of Alzheimer’s disease who meet specific cognitive and biological criteria. To qualify, you must have mild cognitive impairment or mild dementia—measured on the Mini-Mental State Examination (MMSE) score of 20 to 28—and confirmed amyloid plaques in the brain, detected through positron emission tomography (PET) or cerebrospinal fluid testing. Additionally, tau pathology must be present, confirmed through 18F-flortaucipir PET imaging.
A 64-year-old woman diagnosed with mild cognitive impairment who shows amyloid accumulation on brain scans, for example, would be a candidate if she meets these criteria and has no serious heart, liver, or kidney disease that would make treatment unsafe. Once enrolled, donanemab requires a comprehensive monitoring program. Patients receive regular intravenous infusions over approximately 30 minutes every four weeks, with a titration schedule (starting at 700 mg for the first three doses, then 1,400 mg for ongoing maintenance). Throughout treatment, multiple brain MRI scans, PET imaging every six months, cognitive assessments, and blood pressure monitoring track whether the drug is working and whether potentially serious side effects—particularly amyloid-related imaging abnormalities (ARIA)—are developing.
Table of Contents
- Who Qualifies for Donanemab: Cognitive Stage and Biomarker Confirmation
- Brain Imaging Tests Required Before You Start Treatment
- Amyloid and Tau Pathology: Understanding What the Brain Imaging Shows
- The Donanemab Dosing Schedule: From Titration to Maintenance
- Monitoring for Amyloid-Related Imaging Abnormalities: The Primary Safety Concern
- MRI Surveillance During Donanemab Treatment: Detecting Safety Signals Early
- Ongoing Clinical and Laboratory Monitoring Throughout Treatment
Who Qualifies for Donanemab: Cognitive Stage and Biomarker Confirmation
Not everyone with Alzheimer’s disease can take donanemab. The treatment is specifically designed for early symptomatic disease, meaning patients must have mild cognitive impairment or mild dementia stage at the time of enrollment. This is more restrictive than some might expect: people with normal cognition but brain amyloid on imaging are excluded, as are those with moderate to severe dementia. The MMSE score requirement of 20 to 28 excludes both those with minimal cognitive impairment and those with advanced cognitive decline. The second major requirement is biomarker confirmation.
Amyloid plaques must be objectively detected, either through amyloid PET imaging showing a burden of at least 37 Centiloids (a standard measurement of amyloid load), or through analysis of cerebrospinal fluid collected via lumbar puncture. Tau pathology must also be confirmed—not suspected from clinical symptoms alone, but documented on 18F-flortaucipir PET imaging. This dual biomarker requirement means that an MMSE score alone is insufficient; a patient could have a qualifying MMSE score but still not be eligible if imaging fails to show amyloid and tau pathology. APOE genotyping—a blood test revealing whether someone carries the APOE4 genetic variant—is required before treatment starts. This is not an exclusion criterion, but rather a risk stratification tool. People who carry one or two APOE4 alleles face higher risk of developing amyloid-related imaging abnormalities, so their baseline status and ongoing monitoring may differ from non-carriers.
Brain Imaging Tests Required Before You Start Treatment
Before a single infusion of donanemab, two types of brain imaging are mandatory. First, you need amyloid PET imaging using one of three FDA-approved tracers: 18F-florbetaben (Neuraceq®), 18F-florbetapir (Amyvid®), or 18F-flutametamol (Vizamyl®). These tracers bind to amyloid plaques, making them visible to the PET camera. The imaging is assessed using a binary visual read—”positive/elevated” or “negative/non-elevated”—rather than requiring a precise numerical measurement, though the 37 Centiloid threshold guides the classification. This PET scan establishes that amyloid is actually present, confirming the biological basis for treatment.
Second, a baseline MRI of the brain is required. This serves multiple purposes: it establishes a starting point for tracking any brain changes, identifies any pre-existing microhemorrhages or signs of amyloid-related imaging abnormalities, and ensures that certain safety exclusion criteria are met. People with more than four cerebral microhemorrhages or more than one area of superficial siderosis (iron deposits in the brain from prior bleeds) are excluded from treatment, as these findings suggest a higher inherent risk of bleeding complications from anti-amyloid therapy. One critical limitation: not all imaging centers are equipped to perform these specialized PET scans. Rural areas and smaller medical centers may lack access to amyloid PET imaging, requiring patients to travel to academic medical centers or larger hospital networks for baseline evaluation.
Amyloid and Tau Pathology: Understanding What the Brain Imaging Shows
Amyloid plaques and tau tangles are the pathological hallmarks of Alzheimer’s disease, and donanemab specifically targets amyloid accumulation. Amyloid-beta proteins clump together outside brain cells, forming extracellular plaques, while tau proteins misfold and accumulate inside cells, forming intracellular tangles. These pathological processes cause inflammation and neurodegeneration, leading to cognitive decline. Modern PET imaging makes it possible to visualize these abnormalities in living patients before they cause severe damage.
The 37 Centiloid threshold used for eligibility represents a moderate amyloid burden—high enough to confirm Alzheimer’s pathology, but at a stage where cognitive symptoms are still early and the potential for cognitive stabilization or slowing of decline exists. Patients with minimal amyloid on imaging or those already deeply into cognitive decline may not benefit from donanemab in the same way. The presence of tau pathology is equally important: recent research indicates that amyloid and tau together drive cognitive deterioration more aggressively than amyloid alone, so confirming tau presence ensures that donanemab therapy is addressing a critical component of the pathology driving symptoms. A 70-year-old man with memory loss who undergoes amyloid PET and shows significant amyloid deposition, and whose tau PET scan confirms tau tangle formation in memory-related brain regions, meets the biomarker criteria for donanemab therapy—meaning his cognitive decline is directly linked to these pathological accumulations that the drug can potentially address.
The Donanemab Dosing Schedule: From Titration to Maintenance
Donanemab is administered intravenously every four weeks, but the dose escalates over the first three infusions. The updated FDA-approved label, effective as of July 2025, requires a titration phase to reduce the risk of amyloid-related imaging abnormalities, particularly amyloid-related imaging abnormality-edema (ARIA-E). The initial phase delivers 700 mg per infusion for doses 1, 2, and 3, allowing the body and brain to adjust to the anti-amyloid treatment. Beginning with the fourth infusion, the maintenance dose increases to 1,400 mg per infusion, which continues every four weeks for as long as treatment continues. Each infusion takes approximately 30 minutes to administer, with patients monitored for a minimum of 30 minutes afterward for any acute infusion reactions.
This infusion schedule means that patients commit to a significant ongoing time investment—a half-day appointment every month—along with the associated travel, time off work, and logistical coordination. For someone already dealing with early cognitive impairment, coordinating monthly clinic visits can itself be cognitively and physically taxing. The transition from 700 mg to 1,400 mg represents a trade-off between efficacy and safety. The higher maintenance dose is more effective at clearing amyloid from the brain, but it also carries a higher risk of ARIA. The titration phase was introduced specifically because earlier experience showed that jumping directly to higher doses increased ARIA-E rates; the gradual increase gives the brain a chance to adapt while still achieving therapeutic amyloid clearance.
Monitoring for Amyloid-Related Imaging Abnormalities: The Primary Safety Concern
The most significant complication of donanemab therapy is amyloid-related imaging abnormalities (ARIA), a category encompassing two distinct problems. ARIA-E (edema or effusion) occurs when fluid accumulates in or around the brain tissue, visible on MRI as areas of swelling. ARIA-H (microhemorrhages and hemosiderin deposition) occurs when tiny bleeds develop in the brain due to amyloid-related changes in blood vessel walls. In the TRAILBLAZER-ALZ 2 clinical trial that led to FDA approval, 20 to 24 percent of patients treated with donanemab developed ARIA-E, and 27 to 31 percent developed ARIA-H, though most events were mild to moderate and asymptomatic. This is a critical limitation: roughly one in four to one in three patients will develop imaging signs of amyloid-related brain changes during treatment, even if they have no symptoms.
Most of these events are detected only on MRI, meaning the patient may be unaware that any change has occurred. However, symptomatic ARIA—causing headache, confusion, memory loss, or visual changes—is less common, occurring in roughly 3 to 5 percent of treated patients. When symptoms do develop, they usually appear within the first few infusions; approximately 80 percent of serious ARIA events occur within the first three doses. Risk factors for ARIA include carrying the APOE4 genetic variant, having higher baseline blood pressure (mean arterial pressure above 107 mm Hg increases ARIA-E risk by 70 percent), and baseline imaging findings suggesting borderline cerebral amyloid angiopathy. Notably, patients already taking antihypertensive medications have a 40 percent reduction in ARIA risk compared to those with untreated hypertension, demonstrating that blood pressure management is a modifiable and important factor during donanemab therapy.
MRI Surveillance During Donanemab Treatment: Detecting Safety Signals Early
MRI scans are ordered before the second, third, fourth, and seventh infusions to detect ARIA early, when it is still asymptomatic and manageable. In patients carrying APOE4, an additional MRI is performed before the 12th dose. The rationale is straightforward: because ARIA is usually asymptomatic, regular imaging is the only way to know whether it is developing. If an MRI shows early ARIA-E or ARIA-H, the clinical team may slow the infusion schedule, temporarily hold treatment, adjust antihypertensive medications, or discontinue donanemab—potentially preventing progression to symptomatic ARIA. Treatment stopping criteria based on amyloid PET imaging are also used to guide duration of therapy.
Patients receive amyloid PET scans approximately every six months during treatment. If amyloid burden drops below 11 Centiloids on a single scan—indicating substantial amyloid clearance—treatment may be stopped. If amyloid remains between 11 and 24 Centiloids on two consecutive PET scans without further declining, treatment is typically discontinued as well. The goal is to treat until meaningful amyloid clearance is achieved, then stop to avoid prolonged exposure to the risk of ARIA. This usually occurs 12 to 18 months into treatment, though the exact timeline varies.
Ongoing Clinical and Laboratory Monitoring Throughout Treatment
Beyond imaging, patients undergoing donanemab therapy require regular clinical evaluations to track cognitive function and monitor for symptoms suggestive of ARIA. Cognitive assessments—typically using brief tests like the Montreal Cognitive Assessment or the Alzheimer’s Disease Assessment Scale—are administered periodically to determine whether cognitive decline has slowed or stabilized. Blood pressure is monitored at each visit, both because elevated pressure increases ARIA risk and because aggressive hypertension management may protect against ARIA development.
Baseline blood pressure at the start of treatment is a key predictor: patients with mean arterial pressure exceeding 107 mm Hg at enrollment face substantially higher ARIA-E risk. For this reason, some centers proactively optimize antihypertensive therapy before starting donanemab and maintain strict blood pressure targets (often aiming for MAP below 100 mm Hg) throughout treatment. Patients with uncontrolled hypertension may be counseled to delay donanemab until blood pressure is better managed, as the added ARIA risk may outweigh the potential cognitive benefits of the drug.
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