ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Metabolic stress and age drive inflammation and cognitive decline in mice and humans.
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 16 papers.
What it found
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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
16 citing papers in PubMed.
- GLP-1 receptor agonists, metabolic syndrome, and Alzheimer's disease: Lessons and opportunities from the EVOKE trials.Journal of neuroendocrinology · 2026Review
- Advances in the Comprehensive Tree Shrew Brain Atlas.Biomolecules · 2026Review
- Special Issue "Neuroinflammation and Neurodegeneration: Molecular Mechanism and Novel Therapy".International journal of molecular sciences · 2026Article
- The Liver-brain Axis: A Three-stage Model Linking MASLD to Cognitive Impairment and Dementia.Journal of molecular neuroscience : MN · 2026Review
- Associations of Dietary Antioxidant and Phytochemical Indices with Cognitive Function: Mediating Roles of Basal Metabolic Rate and Systemic Inflammation.Antioxidants (Basel, Switzerland) · 2026Article
- Association of body mass index, waist circumference, (abdominal) overweight and obesity with sex- and age-specific cognitive function over time-the Doetinchem Cohort Study.International journal of obesity (2005) · 2026Article
- Obesity-driven phosphatidylethanolamine dysregulation impairs neuroimmune crosstalk and accelerates Alzheimer's pathogenesis.Molecular neurodegeneration · 2026Article
- Lung function as a mediator: bridging appendicular skeletal muscle mass and dementia in middle-aged and older Chinese adults.European journal of medical research · 2026Article
- Gait variability as a dual-pathway marker of cognitive-motor dysfunction in older adults with type 2 diabetes mellitus.Frontiers in endocrinology · 2026Article
- High‑fat diet and cognitive dysfunction: Mechanistic insights into diet‑induced neurodegeneration (Review).International journal of molecular medicine · 2026Review
- Ketogenic metabolic therapy: low-carbohydrate interventions as novel neuroprotective strategies for cognitive dysfunction in diabetes.Frontiers in aging neuroscience · 2026Review
- Healthy dietary patterns for prevention of neuropsychiatric disorders: role of inflammatory and metabolic mechanisms.NPJ science of food · 2025Article
- Negative Correlation Between Secreted Phosphoprotein 1 and the Treg/Th17 Ratio in Non-Valvular Atrial Fibrillation.Reviews in cardiovascular medicine · 2025Article
- Decoding adipose-brain crosstalk: Distinct lipid cargo in human adipose-derived extracellular vesicles modulates amyloid aggregation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Association between basal metabolic rate and cognitive function in Chinese older adults: the mediating effect of sarcopenia.BMC geriatrics · 2025Article
- Article
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
introductionMetabolic stressors (obesity, metabolic syndrome, prediabetes, and type 2 diabetes [T2D]) increase the risk of cognitive impairment (CI), including Alzheimer's disease (AD). Immune system dysregulation and inflammation, particularly microglial mediated, may underlie this risk, but mechanisms remain unclear.
methodsUsing a high-fat diet-fed (HFD) model, we assessed longitudinal metabolism and cognition, and terminal inflammation and brain spatial transcriptomics. Additionally, we performed hippocampal spatial transcriptomics and single-cell RNA sequencing of post mortem tissue from AD and T2D human subjects versus controls.
resultsHFD induced progressive metabolic and CI with terminal inflammatory changes, and dysmetabolic, neurodegenerative, and inflammatory gene expression profiles, particularly in microglia. AD and T2D human subjects had similar gene expression changes, including in secreted phosphoprotein 1 (SPP1), a pro-inflammatory gene associated with AD. DISCUSSION: These data show that metabolic stressors cause early and progressive CI, with inflammatory changes that promote disease. They also indicate a role for microglia, particularly microglial SPP1, in CI. HIGHLIGHTS: Metabolic stress causes persistent metabolic and cognitive impairments in mice. Murine and human brain spatial transcriptomics align and indicate a pro-inflammatory milieu. Transcriptomic data indicate a role for microglial-mediated inflammatory mechanisms. Secreted phosphoprotein 1 emerged as a potential target of interest in metabolically driven cognitive impairment.
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What Socratic holds
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.