Emerging treatments
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Guide de pratique clinique pluridisciplinaire relatif à la collaboration dans la dispense de soins aux personnes âgées démentes résidant à domicile et leurs aidants prochesPublished by: Groupe de Travail Développement de recommmandations de première ligneLast published: 2017Multidisciplinaire richtlijn voor thuiswonende oudere personen met dementie en hun mantelzorgersPublished by: Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 2017Lecanemab
Lecanemab is an intravenous anti-amyloid monoclonal antibody that binds with high affinity to soluble and insoluble forms of amyloid beta. It is approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of Alzheimer disease (AD). In a phase 3 trial, lecanemab was associated with moderately less decline in cognition and function after 18 months, as well as reduced brain amyloid burden, compared with placebo. Adverse effects included infusion-related reactions (24.5% of participants) and amyloid-related imaging abnormalities with edema or effusions (13%), as above.[272] Candidates for lecanemab treatment must have confirmed amyloid pathology. In addition, appropriate use recommendations encourage clinicians to obtain apolipoprotein E (APOE) genotyping to better inform risk discussions with patients who are candidates for lecanemab, concerning the risk of amyloid-related imaging abnormalities (ARIA).[273] ARIA is a complication of treatment with monoclonal antibodies; the risk is higher in patients who are APOE e4 homozygotes.[274] In a multicenter, double-blind, phase 3 trial of lecanemab involving people ages 50-90 years with early AD (defined as mild cognitive impairment or mild dementia due to AD), ARIA with hemosiderin deposition (ARIA-H) affected around 16% of patients, and ARIA with edema (ARIA-E) was 13%. The ARIA-E and ARIA-H were largely radiographically mild to moderate. ARIA-E usually presented in the first 3-6 months and was more common in APOE e4 heterozygotes (16.8%) and those who were homozygous (34.5%). Only 3.3% were symptomatic, and 0.7% were serious.[275] Symptoms of ARIA-E include headache, confusion, vomiting, visual disturbance, and gait disturbance.[274] Three deaths due to brain hemorrhages have been reported among patients taking lecanemab.[276] It should be noted that use of antithrombotic drugs in people taking lecanemab is associated with higher incidence of intracerebral hemorrhage, and patients and providers should be warned that administering anticoagulants or thrombolytics increases the risk of hemorrhage.[272] Further studies of lecanemab are ongoing, including a phase 1 study investigating subcutaneous dosing, and a study of use in amyloid-positive asymptomatic individuals.[277][278]
Donanemab
Donanemab is an intravenous anti-amyloid monoclonal antibody that binds to cerebral amyloid beta peptides, promoting amyloid plaque clearance via microglial phagocytosis.[279] Donanemab is approved by the FDA for treatment of early AD, including mild cognitive impairment or mild dementia. In a phase 3 trial that included patients with early symptomatic AD, and tau and amyloid pathology, donanemab significantly slowed clinical progression at 76 weeks in patients with low/medium tau and in a combined population with low/medium and high tau pathology, compared with placebo.[280] ARIA-E occurs in 20% to 24%, and ARIA-H occurs in 27% to 31%, of people receiving donanemab.[281] The FDA approved a more gradual initial dose schedule to help mitigate these risks in July 2025. The EMA approved donanemab in July 2025 for early symptomatic AD in adults who are APOE noncarriers or heterozygotes, after initially refusing a marketing authorization.
Aducanumab
Aducanumab is an intravenous anti-amyloid monoclonal antibody. It is approved by the FDA for the treatment of AD. However, the manufacturer announced in 2024 that aducanumab would be discontinued in the US due to commercial reasons. Aducanumab was never approved by the EMA.
Benzgalantamine
Benzaglanatamine is a prodrug of the acetylcholinesterase inhibitor galantamine. It has been approved by the FDA (but not the EMA) to treat mild to moderate AD, and has been developed to reduce the risk of gastrointestinal adverse effects compared with galantamine.
Anti-amyloid vaccine
ACI-24.060 is an investigational anti-amyloid vaccine that induces a polyclonal antibody response against two different forms of amyloid beta. Phase 1 and 2 trials in people with prodromal AD and people with Down syndrome are in progress.[282]
Laromestrocel
Laromestrocel is an investigational allogeneic mesenchymal stem cell therapy. It has received regenerative medicine advanced therapy designation by the FDA. One phase 1 study demonstrated that patients treated with laromestrocel had improved neurocognitive assessment scores compared with placebo. Patients treated with laromestrocel also had an improvement in fluid-based and imaging biomarkers.[283] A phase 2 trial is under way.[284]
Troculeucel
Troculeucel is an autologous natural killer (NK) cell therapy. A phase 1 study showed that NK cells produced in this way could internalize and degrade amyloid beta aggregates and alpha-synuclein aggregates, kill activated T lymphocytes, and produce immune modulatory cytokines.[285] A phase 2 study of troculeucel use in the treatment of moderate AD is in progress.[286] Troculeucel has received fast-track designation from the FDA.
Treatments for apathy
There is some evidence that the stimulant methylphenidate is effective for treating apathy associated with AD.[287] Other drugs with possible beneficial effects for apathy include olanzapine, cholinesterase inhibitors, choline alphoscerate, citalopram, memantine, and mibampator (an investigational drug), but more evidence is needed.[288]
Noninvasive brain stimulation
Noninvasive brain stimulation techniques, notably repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have been investigated for effects on cognition and neuropsychiatric symptoms in patients with AD. Beneficial effects and good tolerability have been reported, but studies have been small and heterogeneous. Larger-scale studies and investigation of optimal stimulation parameters are required.[289][290][291]
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