New disease-modifying treatments for Alzheimer’s disease: do they represent a paradigm shift with unforeseen chokepoints and millions of untreated patients?

Introduction

Widespread regulatory approvals of the first two disease-modifying treatments (DMTs) for mild cognitive impairment (MCI)/early-Alzheimer’s disease (AD) generated robust enthusiasm from patient advocacy groups, as well as scientists, researchers and clinicians all around the world. These approvals generated positive coverage in both the scientific and lay-press. Paradoxically, the number (e.g., percentages) of patients in Europe, the United Kingdom (UK) and America that have successfully qualified for and received either of these medicines has been anemic.

Background

We investigated the degree to which the minimal patient utilization of the new DMTs for AD is a result of perceived modest efficacy/benefits coupled with safety concerns, i.e., amyloid related imaging abnormalities (ARIA) and a conventional risk-benefit assessment; or, is something more complicated happening, such as a multifactorial treatment paradigm shift?

Methods/Assessment:Our initial telephonic survey (in the US), resulted in semi-consistent feedback regarding the logistical and systemic ‘hurdles’ associated with patients pre-qualifying to receive lecanemab or donanemab. These included, and were not limited to, pre-screening and screening assessments such as blood-based biomarkers (BBMs), cerebrospinal fluid (CSF), positron emission tomography (PET), including a radioactive tracer, sometimes genetic testing (plus pre-test counseling) and infusion-related logistics. Some of the larger health maintenance organizations (in the US 1^st QTR 2026) were not offering either imaging or BBMs. Our comprehensive literature search illuminated a wide array of contextual “hurdles,” throughout the European Union (EU) and UK. Disparate systemic hurdles translate into essentially the same net patient-related outcomes. In the EU, socioeconomic status (SES) impacts vary widely by country: in Germany a moderate impact; Italy a much larger impact, whereby wealth strongly correlates with a faster diagnosis and access to private care. Sweden has the highest rated access with the lowest SES impacts. Yet, their chokepoint is limited access to specialists (i.e., capacity constraints, not affordability), plus large geographic/regional differences.[1], [2], [3] The US system has different inequities. Socioeconomic status is the number one determinant of seeing a dementia specialist (x 2) and being more likely to receive an amyloid PET (x 2-to-3). Income and education, followed by race/ethnicity and geography (urban versus rural), with rural patients being 50-to-70% less likely to receive a DMT. Additional factors include infrastructure scarcity, i.e., infusion chairs, dementia specialists and MRI + PET capacities.[4] In the UK, access is limited by Health Technology Assessments (HTAs) determined by National Institute for Health Care and Excellence (NICE).

Conclusions

A compelling case can be made that the introduction of DMTs for the treatment of MCI/early-AD clearly represents a global paradigm shift. In the EU, hurdles pertain to system navigation and national decisions. In the US, SES creates a multi-step funnel whereby disparities impact each stage. In the UK, where cost effectiveness is monitored closely, SES impacts are more subtle yet do have an impact. While “top-line” global eligibility for a DMT may be as low as 5-18%, in early 2026 less than 1% of patients are receiving a DMT and in some EU countries it is almost 0%.

References

Kim, S, et al. (2026), “Policies for people with dementia across OECD countries,” OECD Health Working Papers, No. 190, OECD Publishing, Paris, https://doi.org/10.1787/e41e6eaa-en.
Tideman, P, Karlsson, L, Strandberg, O, et al., Primary care detection of Alzheimer’s disease using a self-administered digital cognitive test and blood biomarkers. Nat Med 31, 4131-4139 (2025). https://doi.org/10.1038/s41591-025-03965-4.
Vigneswaran S, Vijverberg EGB, Barkhof F, et al., “Real World” eligibility for anti-amyloid treatment in a tertiary memory clinic setting, Alzheimer’s Dementia 2025 Jun 12; e70375. https://doi.org/10.1002/alz.70375.
Jack CR, Andrews JS, Beach TG, et al., Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimer’s Dementia 2024 Aug;20:5143-5169. https://doi.org/10.1002/alz.13859.