Lecanemab and donanemab slow Alzheimer’s decline, but is the benefit worth the cost?

New research shows that Lecanemab and Donanemab can delay cognitive decline and expand the independence of patients in daily activities. But with high costs and risks, are these treatments really useful for the patients and their families of Alzheimer’s?

Study: Assessment of the clinical significance of delaying CDR-SB progression with disease-modifying therapies for Alzheimer’s disease. Image Credit: Shutterstock AI Generator / Shutterstock.com

A recent Alzheimer and dementia Study is investigating the effects of treatment at the time that patients with Alzheimer’s disease (AD) spend with independent in the basic activities of daily life (Badls) and instrumental activities of daily life (IADLS).

Current treatments for AD

Ad is a neurodegenerative disorder characterized by cerebral accumulation of amyloid and tau pathology, which causes synaptic and neuronal injury, leading to progressive dementia. Various therapies, including anti-amyloid monoclonal antibodies, have been developed to reduce cerebral amyloid burden that can delay the AD progression.

In July 2023, the United States approved Food and Drug Administration (FDA) Lecanemab as a disease -modified therapy (DMT) to combat early symptomatic AD. Shortly thereafter, in July 2024, Donanemab was also approved. In some cases, however, both treatments are associated with minimal clinical relevance when slowing down the progression of dementia.

Both Lecanemab and Donanemab are expensive treatments that can increase the risk of amyloid-related neuroimaging abnormalities (Aria). As a result, some doctors are reluctant to initiate these therapies, because each treatment is needed to demonstrate clinical significance to weigh against potential risks and costs.

Assessing the severity of the advertisement

Clinical Dementia Rating (CDR) is a global scale that is used to determine the dementia status and its severity by measuring the degree of cognitive loss in different domains. These domains include memory, judgment, orientation and problem solving, together with functional skills in community matters, home and personal care.

Each CDR domain is assessed from zero to three, as a result of healthy and severely reduced cognition. The summary of the scores of the individual CDR domains or “boxes” yields the CDR sum of boxes (CDR-SB), a continuous size with scores ranging from zero to 18.

Although there is no clear consensus on a ‘clinical meaningful’ advantage for advertisement dementia, cognition and job performance must be assessed to understand the benefits of advertising treatment. Clinical benefits explained in terms of statistical significance do not always help healthcare providers or family members to understand the treatment results. As a result, other statistics such as IADLs and Badls can be used to quantify functional independence in AD patients.

About the study

The current longitudinal study was conducted in the Knight Alzheimer Disease Research Center (KNIGHTADRC) at Washington University. Both cognitively unscathed and cognitively reduced community persons who corresponded to undergoing amyloid positronemissietoMography (PET) and lumbar puncture (LP) were included in the analysis. All participants in the study also gave cerebrospinal liquid (CSF) samples for amyloid beta (AP) and Tau protein rating.

All participants underwent clinical and cognitive reviews to achieve the CDR score. A clinical diagnosis of ad -dementia was determined based on standard criteria and a global CDR score.

Study findings

This study included 282 participants, 67% of whom had very mild ad -dementia and 33% with mild AD dementia, which was scored with a CDR of one. About 56% of the research cohort was male, 88% were non-Spanish white and 10% were black or Afro-American.

Most CDR 0.5 participants were independent, while only 40% of the CDR 1 participants were independent. At the start, almost all participants were independent in Badls.

Four IADL components were considered as functions of the CDR-SB score, which estimates the level of independence. These components include paying bills, driving, remembering medicines/appointments and meal preparation.

Based on this approach, about 50% of the participants in the study dependent. Some participants were able to prepare their meals independently and remember appointments/medication at a higher CDR-SB score, but could not pay bills and drive efficiently.

A strong relationship between CDR and ADLs was observed. About 93% of the participants with CDR-SB of less than 4.5 were independent in IADLs, while 87% of the participants with CDR-SB of more than 4.5 had no independence in IADLs.

Moreover, 97% of the participants with CDR-SSB were less than 11.5 independent in Badls. For comparison: 85% of the participants with CDR-SB of more than 11.5 showed no independence in Badls.

The average annual CDR-SB increase was 1.30. However, when this metric was modeled as a function of Baseline CDR, the CDR-SB increased by 1.05 every year for people with CDR 0.5 and one at the start. In the course of time, a linear increase in CDR-SS was observed over time.

The expected time to lose independence in IADLs was approximately 29 months. Interestingly, the extra years of independence in IADLs and Badl’s correlated with lecanemab or donanemab treatments, which can be due to a slower repeat rate in CDR-SB.

Based on a consistent decrease in the speed of CDR-SB score after treatment, an extra 10 and eight months of independence in IADL’s associated with Lecanemab and Donanemab treatments were respectively. For the treatment of Donanemab, another 13 months of independence in IADLS was observed for the low/medium Tau Pet group, while four months of independence in IADLs were measured for the High Tau Pet.

Conclusions

The current study offers new insights into the relationship between CDR-SB scores and functional independence. These findings also emphasize the clinical significance of AD treatments and whether patients and their families can make better informed treatment decisions.