What are the FDA‑approved treatments for Alzheimer’s disease and what do they actually do?
Executive summary
Current FDA‑approved treatments for Alzheimer’s fall into two broad groups: long-standing symptom‑relief drugs (cholinesterase inhibitors and memantine) and newer disease‑modifying anti‑amyloid monoclonal antibodies such as lecanemab (Leqembi®) and donanemab (Kisunla™), with an additional FDA‑approved drug for agitation (brexpiprazole/Rexulti®) [1] [2] [3] [4]. Symptom drugs temporarily improve thinking, memory or function but do not slow the disease, whereas the anti‑amyloid antibodies reduce brain amyloid and have shown modest slowing of clinical decline in early Alzheimer’s with specific risks and monitoring requirements [5] [2] [3].
1. Symptom‑management medicines: what they are and what they do
Three cholinesterase inhibitors—donepezil (Aricept), rivastigmine (Exelon®) and galantamine (Razadyne)—approved for mild to moderate Alzheimer’s, raise brain acetylcholine to modestly improve cognition, behavior and daily function for months but do not change the disease course, and are often used throughout illness stages [1] [6] [5]. Memantine (Namenda®), an NMDA receptor antagonist approved for moderate to severe Alzheimer’s, modulates glutamate signaling to help preserve certain functions (for example, toileting independence for some patients) and may be combined with cholinesterase inhibitors because it works by a different mechanism [1] [7]. The clinical benefit of these drugs is generally symptomatic and time‑limited—measured in months of preserved function rather than halting neurodegeneration [8] [5].
2. Disease‑modifying anti‑amyloid antibodies: lecanemab and donanemab
Lecanemab (Leqembi®) and donanemab (Kisunla™) are monoclonal antibodies that target beta‑amyloid in the brain; both are indicated for early symptomatic Alzheimer’s (mild cognitive impairment or mild dementia) with confirmed amyloid pathology and were shown to reduce amyloid plaques and modestly slow cognitive and functional decline in clinical trials [2] [3] [9]. Lecanemab received accelerated then full approval after trials showing plaque reduction and a modest slowing of decline at 18 months, and donanemab received traditional approval with evidence of slowing clinical decline in early disease subgroups [2] [3] [9]. Both require confirmation of elevated brain amyloid—typically amyloid PET or cerebrospinal fluid testing—and ongoing safety monitoring, including MRI surveillance, because their benefits were demonstrated only in early‑stage patients [2] [3].
3. Aducanumab and the politics of approval
Aducanumab (Aduhelm) was earlier approved via an accelerated pathway and became a flashpoint because the approval generated debate about clinical benefit versus evidence strength and regulatory standards; it targeted amyloid but its clinical effects and approval pathway were controversial in the scientific and public domains [10] [6]. Reporting and reviews emphasize that while aducanumab removed amyloid, subsequent discussion highlighted uncertainty about the magnitude of meaningful clinical gain and the FDA’s decision framework, illustrating that anti‑amyloid clearance is not a simple surrogate for broad clinical recovery [10] [11].
4. Risks, limits and practical tradeoffs
Anti‑amyloid antibodies can cause serious side effects—amyloid‑related imaging abnormalities (ARIA), including brain swelling and microhemorrhages—that necessitate MRI monitoring and careful patient selection, and their clinical benefit so far is modest (measured in months of slowed decline), not a cure [10] [12] [8]. Symptom drugs carry their own side effects—gastrointestinal upset, cardiac considerations and others requiring monitoring and individualized decisions—and behavioral drugs such as brexpiprazole are approved specifically for agitation in dementia but should be used after non‑drug strategies because of antipsychotic risks [13] [4] [5].
5. How clinicians use these options today
In practice, clinicians still start with symptom‑relief agents for many patients, reserve anti‑amyloid therapies for those with early disease and confirmed amyloid who accept infusion schedules, monitoring and risk, and consider combination or sequential approaches based on stage and goals of care; practical hurdles include access to specialist diagnosis, PET or CSF testing and the infusion and MRI infrastructure needed for monoclonal antibodies [8] [2] [3]. Patient selection, transparent counseling about expected magnitude of benefit, and shared decision‑making around risks, monitoring burden and costs are central to contemporary prescribing [8] [3].
6. Bottom line: modest gains, targeted use, and fast‑moving science
FDA‑approved Alzheimer’s therapies today offer symptomatic relief (cholinesterase inhibitors, memantine), a drug for agitation (brexpiprazole/Rexulti®), and the first disease‑modifying antibodies that clear amyloid and modestly slow decline in early disease (lecanemab and donanemab), but none cure or stop Alzheimer’s and all require careful patient selection and monitoring—evidence and practice are evolving rapidly [5] [4] [2] [3].