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Unravelling Shared Pathways Linking Metabolic Syndrome, Mild Cognitive Impairment, Dementia, and Sarcopenia
Daniela Ceccarelli Ceccarelli, Sebastiano Bruno Solerte. Metabolites, 2025-02-27
Topic: Brain proteins, microglia and lab models
Metabolic syndrome markers, such as insulin resistance and the triglyceride/HDL C ratio, correlate with early cognitive impairment. Insulin resistance is a cause of synaptic dysfunction and neurodegeneration. Conversely, fasting and fasting-mimicking agents promote neuronal resilience by enhancing mitochondrial efficiency, autophagy, and neurogenesis. Proteins acting as cellular metabolic sensors, such as SIRT1, play a pivotal role in aging, neuroprotection, and metabolic health. In AD, β-amyloid accumulation and hyperphosphorylated tau in neurofibrillary tangles can cause metabolic reprogramming in brain cells, shifting from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect in cancer. The interrelation of metabolic syndrome, sarcopenia, and cognitive decline suggests that targeting these shared metabolic pathways could mitigate all the conditions. Pharmacological interventions, including GLP-1 receptor agonists, metformin, and SIRT 1 inducers, demonstrated neuroprotective effects in animals and some preliminary clinical models. These findings encourage further research on the prevention and treatment of neurodegenerative diseases as well as the drug-repurposing potential of molecules currently approved for diabetes, dyslipidemia, and metabolic syndrome.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ceccarelli, D. C., & Solerte, S. B. (2025). Unravelling Shared Pathways Linking Metabolic Syndrome, Mild Cognitive Impairment, Dementia, and Sarcopenia. Metabolites. https://doi.org/10.3390/metabo15030159
Vancouver
Ceccarelli DC, Solerte SB. Unravelling Shared Pathways Linking Metabolic Syndrome, Mild Cognitive Impairment, Dementia, and Sarcopenia. Metabolites. 2025. doi:10.3390/metabo15030159. PMID: 40137124.
BibTeX
@article{ceccarelli2025-40137124,
author = {Ceccarelli, Daniela Ceccarelli and Solerte, Sebastiano Bruno},
title = {{Unravelling Shared Pathways Linking Metabolic Syndrome, Mild Cognitive Impairment, Dementia, and Sarcopenia}},
journal = {Metabolites},
year = {2025},
doi = {10.3390/metabo15030159},
pmid = {40137124},
url = {https://doi.org/10.3390/metabo15030159}
}
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Key findings
- Metabolic syndrome markers, such as insulin resistance and the triglyceride/HDL C ratio, correlate with early cognitive impairment.
- Insulin resistance is a cause of synaptic dysfunction and neurodegeneration.
- Conversely, fasting and fasting-mimicking agents promote neuronal resilience by enhancing mitochondrial efficiency, autophagy, and neurogenesis.
- Proteins acting as cellular metabolic sensors, such as SIRT1, play a pivotal role in aging, neuroprotection, and metabolic health.
- In AD, β-amyloid accumulation and hyperphosphorylated tau in neurofibrillary tangles can cause metabolic reprogramming in brain cells, shifting from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect in cancer.
Why it matters
This review links metabolic syndrome markers such as insulin resistance to early cognitive impairment and describes shared metabolic pathways with sarcopenia and dementia. It notes that drugs including GLP-1 receptor agonists, metformin, and SIRT1 inducers showed neuroprotective effects in animals and some preliminary clinical models, encouraging further research.
Study details
- Evidence strengthModerate
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Metabolites) |
| Journal's citation record | 1 / 4 | Metabolites: journal h-index 117 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 17 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 10.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Sebastiano Bruno Solerte: h-index 19 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Pavia: institution h-index 809 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40137124) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
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