Early treatment of Alzheimer's disease — from established drugs to antibody treatments developed with Japanese involvement

Summary — For many years, Alzheimer's treatment centred on drugs that relieve symptoms, notably donepezil, developed by researchers at Japan's Eisai. Since 2023, antibody drugs that remove amyloid from the brain have been approved in the United States, Japan and elsewhere. Large phase 3 trials confirmed that they slow cognitive decline in patients at the mild cognitive impairment and mild dementia stages; one of them, lecanemab, was co-developed by Eisai of Japan and Biogen of the United States. Managing side effects such as brain swelling and microbleeds remains an important challenge.

Established drugs: relieving symptoms

Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) slow the breakdown of acetylcholine, a neurotransmitter involved in memory and learning, easing decline in cognition and daily function for a period. Donepezil was developed by researchers at Eisai in Japan and has been used in many countries since the late 1990s. At moderate and later stages, memantine, which regulates excessive neuronal excitation, may be added. These drugs relieve symptoms but are considered not to change the course of the disease.

New treatment: antibodies that remove amyloid

In Alzheimer's disease, amyloid-beta begins to accumulate in the brain long before symptoms appear. Antibody drugs are designed to bind this amyloid and clear it through immune action, aiming to be 'disease-modifying' by acting on the disease process itself.

Lecanemab (CLARITY AD phase 3, 2023) — in a randomised, double-blind, placebo-controlled study of about 1,700 people with Alzheimer's disease at the mild cognitive impairment or mild dementia stage, worsening on a scale combining cognition and daily function (CDR-SB) over 18 months was about 27% slower than with placebo, as reported in NEJM. Co-developed by Eisai of Japan and Biogen of the United States, it was approved in the United States and Japan in 2023 and later in Korea and other countries.

Donanemab (TRAILBLAZER-ALZ 2 phase 3, 2023) — in a randomised study of about 1,700 people with early symptomatic Alzheimer's disease, clinical decline was slower than with placebo, as reported in JAMA, with larger effects in early-stage patients with less tau accumulation. It was approved in the United States and Japan in 2024.

Who these treatments are for, and side effects

These treatments are for patients at the mild early stage whose brain amyloid has been confirmed by amyloid PET or cerebrospinal fluid testing. They require regular intravenous infusions, with MRI monitoring for side effects during treatment. The most important side effect is amyloid-related imaging abnormalities (ARIA) — brain swelling or microbleeds seen on MRI. Most cases are symptomless or mild but can occasionally be serious, and risk has been reported to be higher in people with two copies of the APOE ε4 gene. These drugs slow progression; they do not restore function already lost.

Care beyond medication

Alongside drug treatment, managing blood pressure, glucose and cholesterol, supporting hearing and vision, regular exercise, social activity, sleep, and support for families and carers are important. The 2024 report of the Lancet Commission on dementia emphasises that such care helps maintain quality of life after diagnosis too.

Where stem cell research stands

Studies giving mesenchymal stem cells in Alzheimer's disease are under way as early clinical research in several countries, but effects on cognition have not been confirmed in large randomised studies. The treatments whose effects have been confirmed in large trials and that are approved are the antibody drugs and established medicines above. The state of stem cell research is covered on the 'Alzheimer's Dementia' topic page.

Frequently asked questions

Q. Can anyone receive antibody treatment?
Candidates are patients at the mild cognitive impairment or mild dementia stage whose brain amyloid has been confirmed by testing. Where side-effect risk is higher — for example many microbleeds on pre-treatment MRI or use of blood-thinning medicines — the decision is made with particular care. Eligibility is decided by the medical team based on test results.

Q. Will treatment improve memory?
Antibody drugs slow the progression of the disease. What trials showed is slower decline than with placebo, not recovery of memory already lost — which is why diagnosis as early as possible is emphasised.

Q. What does treatment involve?
Intravenous infusions at the clinic at set intervals, with regular MRI scans, especially early in treatment, to check for side effects. Treatment duration, dosing interval and insurance coverage differ by drug and country, so check with the medical team.

Q. Can it be used with existing drugs?
In the trials, many participants also took established drugs such as donepezil. Whether to combine them is decided by the medical team according to the individual's condition.

How to look up clinical trial information

Ongoing and completed clinical trials can be checked on public registries. ClinicalTrials.gov, run by the U.S. National Library of Medicine, and jRCT, run by Japan's Ministry of Health, Labour and Welfare, publish each study's purpose, eligibility criteria, intervention, outcomes, institutions and status. Results are later published as journal papers, and the reference links below this article lead to the original information. It is also worth knowing that interventions not publicly registered are difficult to verify from outside, in both design and results.

The above summarises published papers and public-agency materials. Company and institute names are given to identify sources, not to introduce or recommend any medical institution or product. Please discuss the suitability and risks of treatment with your medical team.

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