Every row of the evidence table

The review's subject is the harm itself: brain swelling and microbleeds caused by the drugs.

Prespecified and post hoc re-analyses of a trial already reported elsewhere, so this is not independent evidence.

A statistically detectable but very small cognitive effect (ADAS-Cog SMD -0.11) alongside 107 more cases of ARIA-E per 1,000. The reviewers' own conclusion is that removing amyloid does not seem to produce clinically meaningful effects — the sharpest disagreement in this table with how the individual trials were reported.

Mechanistic multi-omic profiling of blood from three ARIA-positive patients and three matched controls on lecanemab. It describes a clonally expanded cytotoxic CD8+ T-cell signature and estimates no clinical effect.

Direction is for lecanemab in mice: it significantly reduced amyloid pathology and neuritic damage, an effect absent with Fc-silenced antibody or without microglia despite intact plaque binding. Mouse work with no human outcome.

An initial negative opinion was reversed on re-examination, with use restricted to APOE4 heterozygotes and non-carriers. The EPAR describes ARIA as affecting more than 1 in 10 people without giving a percentage.

Phase Ib/IIa biomarker result in 13 people; no cognitive outcome measured.

Against placebo: ARIA-E 24.4% vs 1.9%. Risk tracks APOE4 status and baseline imaging.

Direction is for the slower titration schedule against standard dosing, on the drug's own side effect. Amyloid reduction was comparable.

An open-label extension: after 18 months everyone is on the drug, so the comparison is early-start versus delayed-start, not drug versus placebo.

A single-clinic safety series with no comparison group. It reports how often ARIA and infusion reactions happened in practice, which is useful, but it cannot estimate an effect of the drug in either direction.

A mechanistic tissue study describing which microglial states accompany amyloid removal (TREM2 and APOE upregulation correlating with antibody response and clearance; complement signalling contributing). It estimates no effect of immunisation on a clinical outcome.

Corporate announcement discontinuing a product and terminating its confirmatory trial. It reports no clinical outcome, so no direction exists to record.

CHMP refused the drug, then on re-examination recommended it only for people with one or no APOE4 copy, where the ARIA rates are lower. Benefit on cognition and harm from ARIA in the same document, with the restriction as the regulator's way of balancing them.

Benefits were statistically present but every one fell below the minimum clinically important difference, against a number needed to harm of 9 for ARIA-oedema. Agrees with the Cochrane review and not with the trial reports.

Approved on amyloid reduction (surrogate) while reporting higher ARIA rates than placebo; the notice reports no cognitive outcome.

Less decline than placebo, alongside infusion reactions and ARIA.

Phase 1 dose-finding. The outcome is amyloid clearance; no cognitive outcome was measured.

Two identically designed trials disagreed: EMERGE met its primary endpoint, ENGAGE did not.

A coverage determination. It sets the conditions under which Medicare pays and reports no effect estimate.

Benefit is on the surrogate marker only: the approval rested on amyloid reduction, not on confirmed clinical benefit, and the confirmatory trial was later terminated.