Therapeutic time window of disease‐modifying therapy for early Alzheimer's disease
Abstract Introduction Recently approved disease‐modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These criteria define a limited “therapeutic time window,” after which patients...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-04-01
|
| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/trc2.70102 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849682948456972288 |
|---|---|
| author | Saki Nakashima Kenichiro Sato Yoshiki Niimi Ryoko Ihara Kazushi Suzuki Atsushi Iwata Tatsushi Toda Takeshi Iwatsubo for Alzheimer's Disease Neuroimaging Initiative |
| author_facet | Saki Nakashima Kenichiro Sato Yoshiki Niimi Ryoko Ihara Kazushi Suzuki Atsushi Iwata Tatsushi Toda Takeshi Iwatsubo for Alzheimer's Disease Neuroimaging Initiative |
| author_sort | Saki Nakashima |
| collection | DOAJ |
| description | Abstract Introduction Recently approved disease‐modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These criteria define a limited “therapeutic time window,” after which patients become ineligible as the disease advances. Understanding factors influencing this window may help clinicians optimize patient management and reduce lost treatment opportunities. Methods We analyzed longitudinal data from two observational cohorts, the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). At each visit, individuals were deemed eligible if they were amyloid‐positive and had a Mini‐Mental State Examination (MMSE) score of 22–30 (lecanemab) or 20–30 (donanemab), plus a Clinical Dementia Rating‐Global Score (CDR‐GS) of 0.5 or 1. We then applied survival analyses and Cox proportional hazards models to estimate time‐to‐ineligibility based on baseline cognitive status. Results Across both datasets, higher baseline CDR‐GS and MMSE were associated with a lower risk of becoming ineligible (pooled hazard ratio of 1.601 for CDR‐GS of 1 vs. 0.5, and pooled hazard ratio of 0.660 per 1‐point increase in MMSE score above the lower limit of eligibility). The estimated 75% survival time for patients with baseline CDR‐GS 0.5 was over 12 months, suggesting only 25% would become ineligible within 12 months. For those with CDR‐GS 1, the estimated 50% survival time was approximately 12 months, depending on the data, indicating that half might become ineligible within 1 year. Discussion We quantitatively outlined the duration of the therapeutic time window for early AD patients who qualify for lecanemab or donanemab, which is significantly influenced by baseline CDR‐GS and MMSE scores. These findings will support more proactive patient management, ensuring timely evaluations and prioritization of patients at higher risk of ineligibility, particularly where DMT access is limited. Highlights We examined the “therapeutic time window” eligibility for disease‐modifying therapy. Longitudinal data from National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to quantify eligibility duration. Higher Clinical Dementia Rating‐Global Score (CDR‐GS) or lower Mini‐Mental State Examination (MMSE) at baseline were associated with shorter window length. Our results will help optimize the management of the wait time for disease‐modifying therapies (DMT) treatment. |
| format | Article |
| id | doaj-art-76cd6825b97e4906a1975ec3ca696eb2 |
| institution | DOAJ |
| issn | 2352-8737 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj-art-76cd6825b97e4906a1975ec3ca696eb22025-08-20T03:24:02ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372025-04-01112n/an/a10.1002/trc2.70102Therapeutic time window of disease‐modifying therapy for early Alzheimer's diseaseSaki Nakashima0Kenichiro Sato1Yoshiki Niimi2Ryoko Ihara3Kazushi Suzuki4Atsushi Iwata5Tatsushi Toda6Takeshi Iwatsubo7for Alzheimer's Disease Neuroimaging InitiativeDepartment of Neurology, Graduate School of Medicine The University of Tokyo Bunkyo‐ku Tokyo JapanDepartment of Neuropathology, Graduate School of Medicine The University of Tokyo Bunkyo‐ku Tokyo JapanDementia Inclusion and Therapeutics The University of Tokyo Hospital Bunkyo‐ku Tokyo JapanDepartment of Neurology Tokyo Metropolitan Institute for Geriatrics and Gerontology Itabashi‐ku Tokyo JapanDivision of Neurology, Internal Medicine National Defense Medical College Tokorozawa‐shi JapanDepartment of Neurology Tokyo Metropolitan Institute for Geriatrics and Gerontology Itabashi‐ku Tokyo JapanDepartment of Neurology, Graduate School of Medicine The University of Tokyo Bunkyo‐ku Tokyo JapanDepartment of Neuropathology, Graduate School of Medicine The University of Tokyo Bunkyo‐ku Tokyo JapanAbstract Introduction Recently approved disease‐modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These criteria define a limited “therapeutic time window,” after which patients become ineligible as the disease advances. Understanding factors influencing this window may help clinicians optimize patient management and reduce lost treatment opportunities. Methods We analyzed longitudinal data from two observational cohorts, the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). At each visit, individuals were deemed eligible if they were amyloid‐positive and had a Mini‐Mental State Examination (MMSE) score of 22–30 (lecanemab) or 20–30 (donanemab), plus a Clinical Dementia Rating‐Global Score (CDR‐GS) of 0.5 or 1. We then applied survival analyses and Cox proportional hazards models to estimate time‐to‐ineligibility based on baseline cognitive status. Results Across both datasets, higher baseline CDR‐GS and MMSE were associated with a lower risk of becoming ineligible (pooled hazard ratio of 1.601 for CDR‐GS of 1 vs. 0.5, and pooled hazard ratio of 0.660 per 1‐point increase in MMSE score above the lower limit of eligibility). The estimated 75% survival time for patients with baseline CDR‐GS 0.5 was over 12 months, suggesting only 25% would become ineligible within 12 months. For those with CDR‐GS 1, the estimated 50% survival time was approximately 12 months, depending on the data, indicating that half might become ineligible within 1 year. Discussion We quantitatively outlined the duration of the therapeutic time window for early AD patients who qualify for lecanemab or donanemab, which is significantly influenced by baseline CDR‐GS and MMSE scores. These findings will support more proactive patient management, ensuring timely evaluations and prioritization of patients at higher risk of ineligibility, particularly where DMT access is limited. Highlights We examined the “therapeutic time window” eligibility for disease‐modifying therapy. Longitudinal data from National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to quantify eligibility duration. Higher Clinical Dementia Rating‐Global Score (CDR‐GS) or lower Mini‐Mental State Examination (MMSE) at baseline were associated with shorter window length. Our results will help optimize the management of the wait time for disease‐modifying therapies (DMT) treatment.https://doi.org/10.1002/trc2.70102ADNIAlzheimer's diseasedisease‐modifying therapyNACCtherapeutic window |
| spellingShingle | Saki Nakashima Kenichiro Sato Yoshiki Niimi Ryoko Ihara Kazushi Suzuki Atsushi Iwata Tatsushi Toda Takeshi Iwatsubo for Alzheimer's Disease Neuroimaging Initiative Therapeutic time window of disease‐modifying therapy for early Alzheimer's disease Alzheimer’s & Dementia: Translational Research & Clinical Interventions ADNI Alzheimer's disease disease‐modifying therapy NACC therapeutic window |
| title | Therapeutic time window of disease‐modifying therapy for early Alzheimer's disease |
| title_full | Therapeutic time window of disease‐modifying therapy for early Alzheimer's disease |
| title_fullStr | Therapeutic time window of disease‐modifying therapy for early Alzheimer's disease |
| title_full_unstemmed | Therapeutic time window of disease‐modifying therapy for early Alzheimer's disease |
| title_short | Therapeutic time window of disease‐modifying therapy for early Alzheimer's disease |
| title_sort | therapeutic time window of disease modifying therapy for early alzheimer s disease |
| topic | ADNI Alzheimer's disease disease‐modifying therapy NACC therapeutic window |
| url | https://doi.org/10.1002/trc2.70102 |
| work_keys_str_mv | AT sakinakashima therapeutictimewindowofdiseasemodifyingtherapyforearlyalzheimersdisease AT kenichirosato therapeutictimewindowofdiseasemodifyingtherapyforearlyalzheimersdisease AT yoshikiniimi therapeutictimewindowofdiseasemodifyingtherapyforearlyalzheimersdisease AT ryokoihara therapeutictimewindowofdiseasemodifyingtherapyforearlyalzheimersdisease AT kazushisuzuki therapeutictimewindowofdiseasemodifyingtherapyforearlyalzheimersdisease AT atsushiiwata therapeutictimewindowofdiseasemodifyingtherapyforearlyalzheimersdisease AT tatsushitoda therapeutictimewindowofdiseasemodifyingtherapyforearlyalzheimersdisease AT takeshiiwatsubo therapeutictimewindowofdiseasemodifyingtherapyforearlyalzheimersdisease AT foralzheimersdiseaseneuroimaginginitiative therapeutictimewindowofdiseasemodifyingtherapyforearlyalzheimersdisease |