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Baseline Physical Frailty Predicts Clinical Outcomes During Lecanemab Therapy in Early Alzheimer's Disease: A Prospective Real-World Cohort Study
Shin J, Park YJ, Lee S, Kang J, Lee S, Lee ES, Jung HN, Ryoo I et al.. Aging and disease, 2026-10-11
Topic: Amyloid, tau and blood-test diagnosis
Background Physical frailty and sarcopenia are recognized as determinants of Alzheimer's disease (AD) progression, but their implications during anti-amyloid therapy remain unclear. We investigated their associations with longitudinal cognitive outcomes, treatment safety, tolerability, and plasma p-tau217 trajectories in patients with early AD receiving lecanemab. Methods This prospective cohort included 187 patients with amyloid-positive early AD who initiated lecanemab at a tertiary memory clinic. Physical frailty was defined using the Short Physical Performance Battery (SPPB), and sarcopenia according to the 2019 Asian Working Group for Sarcopenia criteria. Logistic regression was used for infusion-related reactions (IRRs) and treatment discontinuation, whereas amyloid-related imaging abnormalities (ARIA) outcomes were evaluated using Firth penalized logistic regression because of the limited number of events. Longitudinal cognitive outcomes and plasma p-tau217 trajectories were analyzed using linear mixed-effects models. Results SPPB-defined physical frailty and sarcopenia were associated with faster CDR-SB worsening (β = 1.52 and 1.40 points/year, respectively; both nominal p<0.001; both q<0.001). A greater decline in SNSB-D was observed in participants with SPPB-defined physical frailty (β=-11.36 points/year; 95% CI, -22.38 to -0.34; nominal p=0.044), although this association did not remain statistically significant after FDR correction (q=0.065). Neither exposure was associated with MMSE change. SPPB-defined physical frailty was associated with a higher risk of IRRs (adjusted odds ratio, 4.75; 95% confidence interval, 2.03-11.66; p<0.001), but was not associated with ARIA or treatment discontinuation. No differential plasma p-tau217 trajectories were detected according to baseline SPPB-defined physical frailty or sarcopenia status. Conclusions Baseline SPPB-defined physical frailty was associated with longitudinal clinical progression and IRRs during lecanemab treatment. These findings suggest that SPPB-defined physical frailty may represent a candidate prognostic marker of clinical outcomes during lecanemab therapy and warrant further validation in larger cohorts.
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APA 7th
Shin, J., Park, Y. J., Lee, S., Kang, J., Lee, E. S., Jung, H. N., et al. (2026). Baseline Physical Frailty Predicts Clinical Outcomes During Lecanemab Therapy in Early Alzheimer's Disease: A Prospective Real-World Cohort Study. Aging and disease. https://doi.org/10.14336/ad.2026.0978
Vancouver
Shin J, Park YJ, Lee S, Kang J, Lee ES, Jung HN, et al. Baseline Physical Frailty Predicts Clinical Outcomes During Lecanemab Therapy in Early Alzheimer's Disease: A Prospective Real-World Cohort Study. Aging and disease. 2026. doi:10.14336/ad.2026.0978. PMID: 42970319.
BibTeX
@article{shin2026-42970319,
author = {Shin, J. and Park, Y. J. and Lee, S. and Kang, J. and Lee, E. S. and Jung, H. N. and Ryoo, I. and others},
title = {{Baseline Physical Frailty Predicts Clinical Outcomes During Lecanemab Therapy in Early Alzheimer's Disease: A Prospective Real-World Cohort Study}},
journal = {Aging and disease},
year = {2026},
doi = {10.14336/ad.2026.0978},
pmid = {42970319},
url = {https://doi.org/10.14336/ad.2026.0978}
}
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Key findings
- Results SPPB-defined physical frailty and sarcopenia were associated with faster CDR-SB worsening (β = 1.52 and 1.40 points/year, respectively; both nominal p<0.001; both q<0.001).
- A greater decline in SNSB-D was observed in participants with SPPB-defined physical frailty (β=-11.36 points/year; 95% CI, -22.38 to -0.34; nominal p=0.044), although this association did not remain statistically significant after FDR correction (q=0.065).
- Neither exposure was associated with MMSE change.
- SPPB-defined physical frailty was associated with a higher risk of IRRs (adjusted odds ratio, 4.75; 95% confidence interval, 2.03-11.66; p<0.001), but was not associated with ARIA or treatment discontinuation.
- Conclusions Baseline SPPB-defined physical frailty was associated with longitudinal clinical progression and IRRs during lecanemab treatment.
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Study details
- Study designprospective cohort
- Participants187
- Evidence strengthModerate
How this study scored 67/100
Published in a peer-reviewed journal, and it is a prospective cohort study, followed forward from enrollment. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 39 of the 58 points we could judge it on, which is 67 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Aging and disease) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A prospective cohort study, followed forward from enrollment |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 187 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42970319) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 39 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 39 of the 58 points we could judge it on is 67 out of 100. |
| Total | 67 / 100 | — |
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