AD Treatment Effectiveness

Pat & Dennis Bender Early Dementia Diagnosis & Prognosis Fund

 

J. Dennis Bender

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We support the development of improved diagnostic methods for the early detection and diagnosis of MCI, Alzheimer’s, vascular and other dementias, their likely prognosis, and best treatment options. We focus on the development of Bayesian-based, medical-decision-support systems, comparative-effectiveness research, and the better utilization of these for the above. (After incorporating in KY as a 501(c)3 in 2002, we dissolved that entity in favor of a simplified form of two entirely self-financed, private philanthropies utilizing a Vanguard Charitable Trust for making annual-research-grants for early-dementia-detection and its correct differential-diagnosis and likely-prognosis. They will continue on, after I am long gone, either mentally or physically, with annual grants. Scripps Foundation, Profs. Randall Bateman, James Brewer and others will be our fund’s future research grant advisors. KMK Law is my legal advisor, David L. Bender is my healthcare proxy, Elizabeth Dunn my estate executor, and Zrinko Modrusan my systems administrator.

 (See: https://www.alz.org/alzheimers-dementia/research_progress/earlier-diagnosis)

 

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www.JDBender.org – Dementia Diagnosis Fund (Vanguard Charitable Trust)

 

February 24, 2025

 

 

“The purpose of this study is not to advocate for or against these medications. The purpose of the paper is to put the impact of these medications into context in ways that can help people make the decisions that are best for themselves and their family members.”

 

This model estimated how long currently-available anti-amyloid-treatments might extend functional-independence for people with early-Alzheimer's-disease. While this analysis did not directly investigate loss-of-function in daily-living-activities over-time in AD, but instead related the activities to CDR-SB-scores, regardless it is additional “good news” for all those scoffers regarding the treatment-effectiveness of these new AD-treatments.

Key Takeaways

• Their model estimated how long anti-amyloid-drugs might extend-independent-living for Alzheimer's-patients.
• Patients with low-baseline-impairment could gain 10-13-months-of-independence with treatment.
• Benefits were more-modest for patients with higher-baseline-impairment.

 

 

Neurology>Alzheimer's Disease

Alzheimer's Patients May Gain Months of Independent Living with Treatment

Model Estimates How Long Lecanemab and Donanemab Might Extend Functional Independence

by Judy George, Deputy Managing Editor, MedPage Today - February 19, 2025 - Emailed article

Key Takeaways

• This model estimated how long anti-amyloid drugs might extend-independent-living for Alzheimer's patients.
• Patients with low baseline impairment could gain 10-13 months of independence with treatment.
• Benefits were more-modest for patients with higher-baseline-impairment, [as would be expected.]

 

A model estimated how long anti-amyloid-treatments might extend functional-independence for people with early-Alzheimer's-disease.

The number of months-of-independent-living an Alzheimer's-patient could expect to gain with anti-amyloid-treatment depended on baseline Clinical Dementia Rating Sum of Boxes (CDR-SB) scores and treatment, reported Sarah Hartz, MD, PhD, of Washington University School of Medicine in St. Louis, and co-authors in Alzheimer's & Dementia. CDR-SB scores range from 0-to-18, with higher-scores indicating greater-impairment.

 

For patients with a baseline CDR-SB score of 2, treatment with lecanemab (Leqembi) would extend independence in instrumental activities-of-daily-living (IADLs) – paying-bills, driving, remembering-medications and appointments, and preparing-meals -- for 10-months (95% CI 4-18 months), Hartz and colleagues estimated. Treatment with donanemab (Kisunla) in patients with a baseline CDR-SB-score of 2 who had low-to-medium-tau would extend independence in IADLs by 13-months (95% CI 6-24 months).

Alzheimer's-patients with a baseline CDR-SB-score of 3.5 could expect approximately 4-additional-months (95% CI 2-7 months) of independence in IADLs with lecanemab, and 5-additional-months (95% CI 2-9 months) with donanemab, the researchers said.

"Our findings give a framework for contextualizing the Clinical Dementia Rating Sum-of-Boxes-score for clinical-decision-making with disease-modifying treatments of Alzheimer's-disease-dementia," Hartz and co-authors wrote.

The study arose from questions patients had about trial-results reported for lecanemab and donanemab, both of which are approved to treat early-Alzheimer's-disease. "What people want to know is how long they will be able to live-independently, not something abstract like the percent-change-in-decline," Hartz said in a statement.

 

"The purpose of this study is not to advocate for or against these medications," she continued. "The purpose of the paper is to put the impact of these medications into context in ways that can help people make the decisions that are best for themselves and their family members."

This information can help clinicians and families weigh estimated treatment benefits against risks, the researchers pointed-out.

 

Both lecanemab and donanemab carry serious-adverse-effects, largely centered around amyloid-related-imaging-abnormalities (ARIA) with edema or effusion (ARIA-E) or ARIA-with-microhemorrhages and hemosiderin-deposits (ARIA-H). Serious intracerebral hemorrhages and deaths have been reported with this class of drugs.

 

Hartz and co-authors examined two inflection-points on the continuum between independence and dependence in Alzheimer's-disease. The first was the point at which a person could no longer live independently due to an impaired ability to manage IADLs. The second point was when a person could no longer tend to basic-activities-of-daily-living (BADL) like personal-hygiene.

The researchers studied patients at the Knight Alzheimer Disease Research Center who met eligibility-criteria for recent disease-modifying-trials, following them for an average of 2.9-years.

 

All patients were 60-or-older at baseline and had global Clinical Dementia Rating (CDR) scores of 0.5 or 1, biomarker-confirmation of amyloid-pathology, and at-least-one follow-up CDR-assessment within 5-years. Global-CDR-scores range from 0-to-3; a score of 0.5 indicates very-mild-impairment, and a score of 1 indicates a person is mildly-impaired.

Most participants (67%) had very-mild (CDR 0.5) Alzheimer's-dementia; the rest had mild-Alzheimer's-dementia (CDR 1). The sample included 88% white and 10% Black participants. Overall, 56% were men.

Nearly all participants were independent in BADLs at baseline. Most CDR 0.5 participants (95%) were independent in IADLs, and a minority of CDR 1 participants (40%) were.

For 50% of participants, loss-of-independence in IADLs occurred when CDR-SB-scores exceeded 4.5; loss-of-independence in BADLs occurred when CDR-SB exceeded 11.5.

Overall, the average-annual-CDR-SB-increase was 1.30 (95% CI 1.13-1.48). Scores on the CDR-SB increased by 1.05/year (95% CI 0.85-1.26) for people with a baseline-CDR of 0.5, and by 1.85/year (95% CI 1.70-2.00) for those with a baseline CDR of 1. The researchers estimated the additional-years-of-independence associated with lecanemab or donanemab treatment due to the slower-rates-of-decline in CDR-SB-scores reported in clinical-trials.

The analysis has several limitations, Hartz and co-authors said. Only patients with biomarker-confirmed Alzheimer's-dementia and longitudinal-data were included, potentially limiting the study's generalizability.

The researchers assumed CDR-SB-progression was linear and treatment-effects would occur uniformly. In addition, the analysis did not directly investigate loss-of-function in daily-living-activities-over-time but related the activities to CDR-SB-scores.

Judy George covers Neurology and Neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow 

Disclosures This study was supported by National Institutes of Health grants and awards.

Hartz and co-authors reported no conflicts of interest.

 

Primary Source

Alzheimer's & Dementia

Source Reference:  Hartz SM, et al "Assessing the clinical meaningfulness of slowing CDR-SB progression with disease-modifying therapies for Alzheimer's disease" Alzheimer's Dement 2025; DOI: 10.1002/trc2.70033.

 

2/24/2025 4:13 AM

 

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