The Divergence Between Clinical Markers and Patient Outcomes
The pursuit of a definitive treatment for Alzheimer’s disease has long been centered on the amyloid hypothesis-the theory that clearing amyloid-beta plaques from the brain would arrest cognitive decline. However, a comprehensive review of 17 trials involving more than 20,000 patients has cast significant doubt on this approach. The non-profit organisation Cochrane concluded that these latest treatments “show no clinically meaningful effect” on memory, daily functioning or the overall course of the disease.
This finding highlights a recurring tension in medical regulation: the difference between a surrogate endpoint and a clinical endpoint. While anti-amyloid drugs like Donanemab and Lecanemab successfully remove plaques-producing visually impressive brain scans-the removal of the biomarker does not consistently translate into a tangible improvement in the patient’s quality of life. In public health terms, the ability to alter a biological marker is an insufficient metric if it fails to preserve independence or cognitive clarity. For regulators, that gap between what can be measured in a scanner and what families notice at the kitchen table is where difficult funding and access decisions are now being made.
Systemic Barriers and Healthcare Infrastructure
Beyond the question of efficacy, the integration of these therapies into a national health system presents substantial logistical and safety challenges. The administration of these drugs is not a simple prescription but a resource-intensive clinical process, particularly in publicly funded systems such as the NHS. The burden on healthcare infrastructure includes:
| Requirement/Risk | Impact on Health System |
|---|---|
| Delivery Method | Requires regular intravenous infusions, necessitating specialised clinic space, infusion chairs and trained nursing staff. |
| Safety Monitoring | Frequent MRI or CT scans to monitor for amyloid-related imaging abnormalities (ARIA), such as brain swelling and bleeding, with additional risk in certain genetic subgroups. |
| Annual Cost | Estimated at £60,000 to £80,000 per patient, creating significant and recurring budgetary pressure on the NHS. |
These requirements mean that widespread adoption would not only require massive financial investment but would also strain diagnostic imaging capacity and outpatient infusion services already facing high demand. In practice, any national rollout would force trade-offs with cancer services, stroke care and other time-critical specialties that also rely on scanners, specialist nurses and tightly scheduled day units.
The Tension Between Policy and Public Expectation
The National Institute for Health and Care Excellence (NICE) rejected these drugs for routine NHS use in 2025, citing a lack of cost-effectiveness. Under its technology appraisal framework, NICE must weigh the incremental cost of a treatment against the quality-adjusted life years it delivers, and decide whether that trade-off is acceptable for a tax-funded service. This decision reflects a rigorous adherence to health economics, where the marginal benefit to the patient must justify the opportunity cost to the wider population.
However, this evidence-based approach often clashes with the emotive nature of dementia care, where families measure benefit in conversations preserved and memories retained, not in fractional score changes on cognitive scales. Public demand remains high, with polling suggesting that nearly 70% of people support availability regardless of cost. This sentiment is echoed in policymaking circles. During a Nuffield Trust summit, crossbench peer Louise Casey argued: “I know the NHS can’t afford every drug. But if I was diagnosed with Alzheimer’s disease and a treatment would give me six months to talk to my family and get my affairs in order before the disease took hold, I’m not sure I would call that a small benefit.”
That divergence between technocratic assessment and lived experience is now a live political question: should ministers override arm’s-length bodies in the name of hope, or defend the discipline of rules-based rationing even when it proves deeply unpopular?
Quantifying the Clinical Gap
To understand why regulators view the benefits as “small,” it is necessary to look at the delta between statistical significance and real-world impact. Using Lecanemab as a case study, the data reveals a narrow margin of improvement:
- Reported Slowing: Some studies highlighted a 27% slowing in cognitive decline.
- Actual Scale Impact: On an 18-point scale measuring reasoning, memory, and daily function over 18 months, placebo patients declined by 1.7 points.
- Drug Impact: Patients receiving the drug declined by 1.2 points.
- Net Difference: A 0.5-point difference on an 18-point scale.
In regulatory filings, such differences are statistically detectable and can justify conditional approvals, especially when set against the absence of alternatives. But the clinical relevance-whether a patient or caregiver can actually perceive the difference in daily living-is highly debatable. Clinicians also point to the safety profile: real-world data from early use in the United States show that ARIA-related swelling and bleeding, while manageable in specialist centres, are not trivial risks for older, frailer patients.
Dr Richard Oakley, Associate Director of Research and Innovation at the Alzheimer’s Society, emphasized the need for a broader approach, stating, “Alzheimer’s disease is highly complex and a combination of treatments will likely be needed to target a range of processes involved in its development. Anti-amyloid drugs are just one treatment avenue and not a silver bullet.” For policymakers, that implies an uncomfortable choice between channelling scarce funds into expensive, marginally effective late-stage drugs or rebalancing towards prevention, social care and support services that have clearer, if less headline-grabbing, impacts on quality of life.
Regulatory Vacuums and the Rise of Unverified Alternatives
The failure of high-profile pharmaceutical interventions often creates a vacuum in patient care. When institutional medicine struggles to provide a cure, desperate populations frequently turn to the “brain health” industry. This sector often promotes diet, supplements and lifestyle changes as definitive answers, despite lacking the rigorous trial data required for evidence-based medicine. In the absence of clear guidance, the boundary between legitimate risk reduction advice and commercial overclaiming becomes blurred.
The risk is compounded by concerns over the integrity of early amyloid research, including allegations of fraud. When the boundary between scientific hype and clinical reality blurs, it undermines public trust in healthcare regulation and makes it more difficult for systems to pivot toward more promising, multi-target therapeutic strategies. The danger lies in a system that may be too invested-politically, financially and reputationally-in a single hypothesis to effectively change course, even as the clinical returns diminish.
For governments, the next phase of Alzheimer’s policy will hinge on whether bodies such as the National Institute for Health and Care Excellence technology appraisal process can remain the anchor for difficult decisions, while regulators, research funders and health systems redefine success away from plaque clearance alone and towards outcomes patients and families can actually feel.