ReviewThe journals of gerontology. Series A, Biological sciences and medical sciences2022
Pathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function.
Review in The journals of gerontology. Series A, Biological sciences and medical sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Association of Sarcopenia With Global, Motor, Cognitive, and Swallowing Function Prognosis in Stroke Patients: A Systematic Review and Meta-Analysis.Brain and behavior · 2026Pooled it
- The association between sarcopenia and cognitive impairment in hospitalized older adults: a systematic review.BMC geriatrics · 2025Pooled it
- Factors associated with the risk of falls and their relationship with cognitive function in older adults with cognitive impairment: a cross-sectional study.GeroScience · 2026Article
- A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026Review
- Possible Sarcopenia and Subsequent Cognitive Function in Older Chinese Adults: Limited Evidence for Mediation by Frailty.Geriatrics & gerontology international · 2026Observational
- Temporalis muscle biomarkers from routine brain MRI and risk of dementia in two independent cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Exploring the link between body physiology and cognition: the role of the brain and aging.npj aging · 2026Article
- Association of CT-derived muscle quality with multiple geriatric syndromes in older adults: a cross-sectional study.GeroScience · 2026Article
- The crossroads between osteosarcopenia and intrinsic capacity-a narrative review.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Review
- Impact of appendicular skeletal muscle mass on Alzheimer's disease in relation to age and comorbidities: an 8-year longitudinal follow-up study of a nationwide cohort.Alzheimer's research & therapy · 2026Article
- Proteomic Age Acceleration in Multiple Sclerosis Precedes Symptom Onset and Associates with Severity.medRxiv : the preprint server for health sciences · 2026Article
- Effects of Sarcopenia and Frailty on Cognitive Function, Brain Volume, and Dementia Risk: A Prospective Cohort Study Based on UK Biobank.Dementia and neurocognitive disorders · 2026Article
- The central benefit of physiologically induced ketogenic states.The Journal of physiology · 2026Review
- Effects of sarcopenia on cognitive function in middle-aged and older adults: mediating roles of social participation and instrumental activities of daily living disability.BMC public health · 2026Article
- Randomized, double-blind, placebo-controlled trial of fecal microbiota transplantation from young physically active donors to promote resilient aging: clinical trial protocol (ARMOR study).BMC geriatrics · 2026Article
- Associations of chinese-modified MIND diet with low muscle mass and physical performance among old adults in china: findings from the CLHLS 2018 national survey.Aging clinical and experimental research · 2026Article
- Sex Differences in the Association Between Body Composition and Cognitive Performance in Adolescents With Type 1 Diabetes.Diabetes/metabolism research and reviews · 2026Observational
- Soft tissue changes in Dementia: A comprehensive systematic review.Aging brain · 2026Review
- Obesity-associated gut microbiome influences diet-induced metabolic and cognitive outcomes in older adults.Gut microbes reports · 2026Article
- Article
13 more citing papers are in PubMed but not listed here.
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 at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low skeletal muscle mass is associated with cognitive impairment and dementia in older adults. This review describes the possible underlying pathophysiological mechanisms: systemic inflammation, insulin metabolism, protein metabolism, and mitochondrial function. We hypothesize that the central tenet in this pathophysiology is the dysfunctional myokine secretion consequent to minimal physical activity. Myokines, such as fibronectin type III domain containing 5/irisin and cathepsin B, are released by physically active muscle and cross the blood-brain barrier. These myokines upregulate local neurotrophin expression such as brain-derived neurotrophic factor (BDNF) in the brain microenvironment. BDNF exerts anti-inflammatory effects that may be responsible for neuroprotection. Altered myokine secretion due to physical inactivity exacerbates inflammation and impairs muscle glucose metabolism, potentially affecting the transport of insulin across the blood-brain barrier. Our working model also suggests other underlying mechanisms. A negative systemic protein balance, commonly observed in older adults, contributes to low skeletal muscle mass and may also reflect deficient protein metabolism in brain tissues. As a result of age-related loss in skeletal muscle mass, decrease in the abundance of mitochondria and detriments in their function lead to a decrease in tissue oxidative capacity. Dysfunctional mitochondria in skeletal muscle and brain result in the excessive production of reactive oxygen species, which drives tissue oxidative stress and further perpetuates the dysfunction in mitochondria. Both oxidative stress and accumulation of mitochondrial DNA mutations due to aging drive cellular senescence. A targeted approach in the pathophysiology of low muscle mass and cognition could be to restore myokine balance by physical activity.
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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.