ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
The higher benefit of lecanemab in males compared to females in CLARITY AD is probably due to a real sex effect.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Sex differences inFrontiers in dementia · 2025Pooled it
- Rethinking tau-targeted therapy in Alzheimer's disease: Toward a dual biomarker strategy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Operationalizing Alzheimer's disease trials in the era of targeted therapies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Sex-aware causal inference assessment of the immune system in complex neurodegenerative diseases.Brain : a journal of neurology · 2026Article
- Descriptive Analysis of Retrospective Observational Real-World Evidence of a Monoclonal Anti-Amyloid Therapy Program in a Wide Catchment Specialty Memory Clinic.Neurology and therapy · 2026Article
- Tau-PET and CSF MTBR-tau243 comparisons validate increased tau aggregation in females.European journal of nuclear medicine and molecular imaging · 2026Article
- The Neurology of Menopause.Current neurology and neuroscience reports · 2026Review
- Effect of Parity and β-Amyloid on Cognition and Hippocampal Volume in Postmenopausal Women.Neurology · 2026Article
- Molecular mechanisms underlying amyloid lowering by aducanumab: differential and comparative effects of sex and IgG reveal the post-treatment disease brain.bioRxiv : the preprint server for biology · 2026Article
- Twenty years of sex and gender science in health research: a policy statement from the Organization for the Study of Sex Differences.Biology of sex differences · 2026Review
- Sex differentiated and domain specific patterns of longitudinal cognitive decline across subjective cognitive decline and amyloid positivity groups.medRxiv : the preprint server for health sciences · 2026Article
- A digital twin methodology using retrospective patient data for sample size reduction in Alzheimer's disease clinical trials.Alzheimer's research & therapy · 2026Article
- Insights into the Impact of Low-Dose Ionizing Radiation on Neurodegenerative Disease Progression in In Vivo Models.International journal of molecular sciences · 2026Review
- Clinical impact of the Alzheimer's Disease Neuroimaging Initiative: A review of studies using ADNI data (2023 to June 2025).Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
- Sex and APOE genotype specific brain regional vulnerability to Alzheimer's Disease.GeroScience · 2026Article
- AI-enhanced Centiloid quantification of amyloid PET images.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Sex differences in Alzheimer's disease plasma biomarker levels and clinical utility.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Do Sex Differences in Alzheimer Pathology Extend to Diverse Cohorts?JAMA network open · 2026Article
- Understanding quantitative effects of anti-amyloid therapies on tau biomarkers and functional outcome. Insights from a comprehensive mechanistic quantitative systems pharmacology study.Frontiers in pharmacology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
introductionThe phase 3 trial CLARITY AD found lecanemab slowed cognitive decline by 27%. However, subgroup analyses indicated a significant 31% sex difference in the effect and suggested no or limited effectiveness in females. We used simulations constrained by the trial design to determine whether that difference reflects a pre-existing sex difference in Alzheimer's disease progression or was a random event.
methodsSimulations were generated using linear mixed models of cognitive decline fit to data from Alzheimer's Disease Neuroimaging Initiative participants satisfying CLARITY AD inclusion criteria.
resultsThe statistically non-significant 7.9% smaller cognitive decline rate in our cohort's males versus females does not explain CLARITY AD's 31% sex difference in lecanemab's effect. A ≥ 31% difference occurred randomly in only 12 of our 10,000 simulations (0.0012 probability). DISCUSSION: CLARITY AD's sex difference was probably not random. Lecanemab is likely less effective in females than males, but we cannot conclude the drug is ineffective in females. HIGHLIGHTS: Lecanemab is more clinically effective in males than in females. Forest plots should only report subgroup-specific effects in well-powered subgroups. Trial simulations based on real data enable investigation of subgroup drug effects. We cannot conclude that lecanemab is clinically ineffective in females. A sex difference in lecanemab's efficacy could be linked to its action mechanism.
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