ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Commonly prescribed multi-medication therapies exert sex-specific effects on Alzheimer's disease pathology and metabolomic profiles in App
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 6 papers.
What it found
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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.
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Who cites it
6 citing papers in PubMed.
- Frailty, polypharmacy, deprescribing, and 23-hour activity: insights from a mouse model.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- When treatment becomes risk: polypharmacy and inappropriate prescribing in cognitive impairment in 2379 consecutive patients from a memory clinic.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Observational
- The Use of Statins in Parkinson's and Alzheimer's Disease: A 2021-2025 State-of-the-Art Review of Clinical and Preclinical Evidence.Pharmacology research & perspectives · 2026Review
- Effect of prescribing and deprescribing oxycodone on pain and function in a mouse model of osteoarthritis: impact of polypharmacy and sex on response.bioRxiv : the preprint server for biology · 2025Article
- Commonly prescribed multi-medication therapies exert sex-specific effects on Alzheimer's disease pathology and metabolomic profiles in AppAlzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Polypharmacy is associated with lower progression from MCI to Alzheimer's disease, with sex-specific patterns across drug classes.Alzheimer's & dementia (Amsterdam, Netherlands)Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
introductionPolypharmacy is common among older adults and people with dementia. Multi-medication therapy poses risks of harm but also targets comorbidities and risk factors associated with dementia, offering therapeutic potential.
methodsWe evaluated the effects of two polypharmacy regimens and monotherapies on male and female App
resultsA combination of metoprolol, simvastatin, aspirin, paracetamol, and citalopram improved memory, reduced amyloid burden and neuroinflammation, and modulated AD-associated metabolomic signatures in male mice, with negligible effects in female mice. Substituting two cardiovascular drugs impacted emotional domains but worsened memory, predominantly in female mice. In males, monotherapies could not explain the combination effects, suggesting drug synergy, whereas in female mice, certain monotherapy effects were lost when combined. DISCUSSION: This study uncovers the sex-specific effects of polypharmacy in an AD model, identifying mechanisms and biomarkers that can guide gender-specific use of medicines in dementia prevention and management. HIGHLIGHTS: Two polypharmacy combinations show sex-specific effects on AD pathology and serum metabolomic profiles. Metoprolol+simvastatin+aspirin+paracetamol+citalopram improves memory and amyloid pathology in male mice. Replacing metoprolol and simvastatin with enalapril and atorvastatin eliminates benefits in male mice and impairs memory in female mice. Selected monotherapies produce sex-specific effects but only partially explain the outcomes of the combinations. Metabolomic pathways in serum indicate possible mechanisms and biomarkers for evaluating the effectiveness and safety of personalized therapies in aging and dementia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.