What are the common side effects and risks associated with that Alzheimer’s therapy?
Executive summary
Anti‑amyloid “disease‑modifying” antibodies (notably lecanemab/Leqembi and donanemab) slow cognitive decline modestly but carry meaningful safety risks: infusion‑related reactions (≈26% in some trials), amyloid‑related imaging abnormalities—brain swelling and microbleeds (reported in roughly 12–37% across studies and analyses)—and rare fatalities linked to ARIA [1] [2] [3]. Symptomatic cholinesterase inhibitors still used for mild Alzheimer’s cause common gastrointestinal effects such as nausea, vomiting and diarrhea [4].
1. What clinicians mean by “side effects” and why ARIA dominates the discussion
The defining safety concern for the new anti‑amyloid antibodies is ARIA — a catchall used for brain swelling (ARIA‑E) and small brain bleeds (ARIA‑H) detected on MRI. Multiple outlets report that ARIA occurred in a substantial minority of treated patients (trial averages cited between about 21% and 37% for some antibody programs), with symptomatic cases and a small number of fatalities documented, making ARIA the central clinical risk when weighing treatment [2] [3] [1].
2. Common, more frequent — and usually manageable — reactions
Beyond ARIA, infusion‑related reactions are common with intravenously delivered antibodies. In the lecanemab pivotal trial, 26.4% of participants experienced infusion‑related events (flushing, chills, fever, rash, body aches) compared with 7.4% on placebo; these are usually transient and can be mitigated with pre‑medication (antihistamines, acetaminophen) and clinical monitoring [1] [5].
3. Who is at higher risk — genetics, drugs and monitoring needs
APOE ε4 carriers have an elevated risk of ARIA, and concurrent use of anticoagulants or antiplatelet drugs appears to increase bleeding risk; regulators and associations recommend APOE genotyping and repeat MRI surveillance when using these agents to guide risk/benefit discussions [5] [2] [6]. The need for serial imaging—sometimes every few months—adds logistical burden and informs stricter patient selection in real‑world practice [6] [2].
4. How frequent and how severe are ARIA events in practice?
Reported ARIA frequencies differ by drug and study. Some reports cite ARIA rates up to about 40% for brain swelling and up to 28% for microbleeds in earlier antibody trials; other program averages fall in the 21–37% range. Many ARIA cases are radiographic and asymptomatic, but clinicians have recorded symptomatic ARIA and rare deaths, which is why professional caution and boxed warnings appear in prescribing materials [3] [2] [6].
5. Trade‑offs: modest slowing of decline versus potentially serious harms
Experts and reporting underscore a stark trade‑off: these antibodies can modestly slow progression in early disease but do not stop Alzheimer’s and do not help everyone. That modest clinical benefit must be balanced against the nontrivial risk of ARIA, occasional severe outcomes, and treatment burdens (infusions/injections, MRIs, genetic testing) when deciding who should be offered therapy [7] [3] [8].
6. Other approved and older treatments: different side‑effect profiles
Cholinesterase inhibitors—still first‑line for many with mild AD—cause mainly peripheral side effects such as nausea, vomiting and diarrhea; these are common but generally tolerable and differ qualitatively from the neurologic bleeding/swelling risks of antibodies [4]. This contrast matters when comparing symptom‑management drugs with disease‑modifying immunotherapies [4] [9].
7. Uncertainties, disagreements and what reporting omits
Available sources disagree on exact ARIA frequencies across drugs and trials (ranges and averages differ by article and antibody) and note that trial populations and real‑world patients are not identical, limiting direct extrapolation [2] [3]. Available sources do not mention long‑term safety beyond several years of follow‑up for most patients, so durability of both benefit and harms remains incompletely reported (not found in current reporting).
8. Practical implications for patients and clinicians
Clinicians now commonly weigh APOE status, anticoagulant use, and ability to adhere to MRI monitoring before prescribing. Some centers are experimenting with dose adjustments or reduced dosing frequency to lower ARIA risk, but these strategies are in evolution and subject to ongoing clinical debate [2] [1].
Bottom line: the new anti‑amyloid therapies introduce the first widely available disease‑modifying option with measurable, modest benefit; they also introduce a unique safety profile centered on ARIA and imaging‑detected brain injury that requires careful patient selection, genetic and imaging surveillance, and frank discussions about trade‑offs [1] [2] [3].