What are the current FDA‑approved treatments for Alzheimer’s and what do they actually do?
Executive summary
The FDA currently recognizes two classes of Alzheimer’s treatments: disease-targeted, anti-amyloid immunotherapies that have been shown to reduce brain amyloid and modestly slow cognitive decline in early-stage disease (lecanemab/Leqembi and donanemab/Kisunla) and longer-standing symptomatic drugs—cholinesterase inhibitors and an NMDA antagonist—that mainly ease cognitive symptoms or behavioral problems without proving disease reversal (donepezil, rivastigmine, galantamine, memantine and combination therapies), plus one atypical antipsychotic approved for agitation (brexpiprazole/Rexulti) [1] [2] [3] [4] [5].
1. What is officially approved right now: the short list
Two monoclonal anti-amyloid antibodies are approved for patients with early symptomatic Alzheimer’s who have confirmed elevated brain amyloid—lecanemab (Leqembi), which the FDA converted to traditional approval after a Phase 3 confirmatory trial, and donanemab (Kisunla), approved for similar early-stage populations and given by periodic IV infusion [1] [2] [3]. The older, symptomatic drugs include acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine—and historically tacrine) and the NMDA-receptor antagonist memantine; donepezil and rivastigmine are approved across several stages, and memantine is used for moderate to severe disease and often combined with cholinesterase inhibitors [6] [4]. For dementia-related agitation there is an FDA approval for brexpiprazole (Rexulti) as a supplemental indication [7] [5].
2. How the new drugs actually work: removing amyloid, not curing neurons
Lecanemab and donanemab are antibodies designed to target and remove aggregated forms of amyloid‑beta from the brain; clinical trials showed they reduce amyloid plaque on PET imaging and produce statistically significant—but modest—slowing of clinical decline over the time windows studied (about 18 months) in people with mild cognitive impairment or mild dementia who have confirmed amyloid pathology [2] [3] [8]. Regulatory summaries and scientific reviews stress that these agents are “disease‑targeted” in intent because they act on a pathological hallmark (amyloid), not that they reverse established neuronal loss; approvals were tied to biomarker reductions and measurable but limited clinical benefit [8] [1].
3. What the older symptomatic drugs actually do for patients
Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) boost signaling by preventing breakdown of acetylcholine and can modestly improve memory or daily functioning for months to years in some people, while memantine regulates glutamate signaling and can help certain patients in later stages maintain abilities such as toileting for additional months; combinations are used because mechanisms differ and may be complementary [6] [4]. These drugs do not remove amyloid or stop disease progression; they mitigate symptoms and may help quality of life and caregiver burden in targeted ways [4] [6].
4. Risks, monitoring and practical limits of anti‑amyloid therapy
Anti‑amyloid antibodies carry important safety risks—most notably ARIA (amyloid‑related imaging abnormalities) that can include brain swelling or microhemorrhages—and require patient selection (confirmation of amyloid pathology) and radiographic monitoring as specified in prescribing information; labeling warns there are no data for initiating treatment outside the studied early stages [2] [1] [9]. Trial effects translated to modest delays in decline (commonly measured as a few months’ worth of benefit at 18 months by some analyses), and manufacturers and commentators caution these therapies do not stop Alzheimer’s or fully restore lost function [10] [11].
5. Controversies, discontinuations and the bigger picture
The pathway to approval has been contentious: aducanumab (Aduhelm) was an earlier accelerated approval that sparked debate and was later discontinued by its manufacturer, illustrating tensions over surrogate endpoints and clinical benefit interpretation [12] [10]. Independent reviewers and journals emphasize that the field has moved toward biomarker‑driven, targeted trials but that clinical benefit remains incremental and expensive, fueling discussions about access, monitoring burdens and real‑world effectiveness [8] [11].
6. Bottom line for the treatment landscape
The FDA now authorizes both disease‑targeted anti‑amyloid immunotherapies for early, biomarker‑confirmed Alzheimer’s and a set of symptomatic drugs for cognitive or behavioral management; the former remove amyloid and modestly slow decline in selected patients but require careful selection and safety monitoring, while the latter ease symptoms without modifying the underlying pathology [1] [2] [4]. Source reporting does not allow judgment outside these documented approvals and trial outcomes; clinicians must weigh individual patient risks, stage of disease and monitoring capacity when deciding on therapy [9] [4].