ArticleAlzheimer's research & therapy2019
Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.
Article in Alzheimer's research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03094546 (Effect of Polyamine-enriched Dietary Supplementation on Cognitive Function and Biomarkers in Elderly Individuals With Subjective Cognitive Decline), which is not on this map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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.
Effect of Polyamine-enriched Dietary Supplementation on Cognitive Function and Biomarkers in Elderly Individuals With Subjective Cognitive Decline
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Trial
- Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.JAMA network open · 2022Trial
- Article
- Spermidine Attenuates Neuroimmune Dysfunction in Gulf War Illness via Modulation of the Gut- Brain Axis.Molecular neurobiology · 2026Article
- Spermidine and Eugenol Modulate Tight Junction and Stemness Markers in Colorectal Cancer Spheroids.International journal of molecular sciences · 2026Article
- LBX1 alters polyamine pathway in adolescent idiopathic scoliosis - a new therapeutic target to mitigate curve progression.Journal of orthopaedic translation · 2026Article
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Sex-Specific Diet-Microbiota Interactions in Ageing: Implications for Healthy Longevity.Nutrients · 2025Review
- Protective Role of Spermidine Against Diabetes-Induced Ovarian and Endometrial Injury via LC3 and Beclin-1 Modulation.Antioxidants (Basel, Switzerland) · 2025Article
- Age-Dependent Redistribution of the Life-Important Enzyme in the Retina: Adult Müller Glial Cells' Endfeet Lack Spermine Synthase Expression.Biomolecules · 2025Article
- Age-Related Cognitive Decline and Dementia: Interface of Microbiome-Immune-Neuronal Interactions.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Review
- Dual Roles of Autophagy in Radiation-Induced Brain Injury: Mechanistic Insights and Therapeutic Implications.CNS neuroscience & therapeutics · 2025Review
- The microbiota-gut-brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets.The FEBS journal · 2025Review
- Spermidine Treatment Improves GRIN2B Loss-Of-Function, A Primary Disorder of Glutamatergic Neurotransmission.Journal of inherited metabolic disease · 2025Article
- Rapamycin enhances CAR-T control of HIV replication and reservoir elimination in vivo.The Journal of clinical investigation · 2025Article
- Spermidine Synthase Localization in Retinal Layers: Early Age Changes.International journal of molecular sciences · 2024Article
- Neural ageing and synaptic plasticity: prioritizing brain health in healthy longevity.Frontiers in aging neuroscience · 2024Review
- The role of Foxo3a in neuron-mediated cognitive impairment.Frontiers in molecular neuroscience · 2024Review
- The involvement of the gut microbiota in postoperative cognitive dysfunction based on integrated metagenomic and metabolomics analysis.Microbiology spectrum · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundGiven the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer's disease. Therefore, it is our primary goal to determine whether spermidine supplementation has a positive impact on memory performance in this at-risk group, as compared with placebo. The secondary goal is to examine the effects of spermidine intake on other neuropsychological, behavioral, and physiological parameters.
methodsThe SmartAge trial is a monocentric, randomized, double-blind, placebo-controlled phase IIb trial. The study will investigate 12 months of intervention with spermidine-based nutritional supplementation (target intervention) compared with 12 months of placebo intake (control intervention). We plan to recruit 100 cognitively normal older individuals with SCD from memory clinics, neurologists and general practitioners in private practice, and the general population. Participants will be allocated to one of the two study arms using blockwise randomization stratified by age and sex with a 1:1 allocation ratio. The primary outcome is the change in memory performance between baseline and post-intervention visits (12 months after baseline). Secondary outcomes include the change in memory performance from baseline to follow-up assessment (18 months after baseline), as well as changes in neurocognitive, behavioral, and physiological parameters (including blood and neuroimaging biomarkers), assessed at baseline and post-intervention. DISCUSSION: The SmartAge trial aims to provide evidence of the impact of spermidine supplementation on memory performance in older individuals with SCD. In addition, we will identify possible neurophysiological mechanisms of action underlying the anticipated cognitive benefits. Overall, this trial will contribute to the establishment of nutrition intervention in the prevention of Alzheimer's disease.
trial registrationClinicalTrials.gov, NCT03094546 . Registered 29 March 2017-retrospectively registered. PROTOCOL VERSION: Based on EA1/250/16 version 1.5.
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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 OpenQuestion graph.