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 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
21 citing papers in PubMed.
- Effects of obesity on brain health and cognition.Nature reviews. Neurology · 2026Review
- Combined Associations of Diabetes and Depressive Symptoms on Cognitive Impairment Risk in the Population Aged 60 or Older: Cross-Cohort Comparisons From NHANES and CHARLS.Psychiatry investigation · 2026Article
- 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
- Association of glymphatic function with 40-Hz neural oscillations, systemic metabolic markers, and cognitive performance in healthy aging adults: An EEG and MRI study.Translational psychiatry · 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
- High‑fat diet and cognitive dysfunction: Mechanistic insights into diet‑induced neurodegeneration (Review).International journal of molecular medicine · 2026Review
- Gait variability as a dual-pathway marker of cognitive-motor dysfunction in older adults with type 2 diabetes mellitus.Frontiers in endocrinology · 2026Article
- Clinical characteristics of subclinical carotid atherosclerosis in middle-aged and elderly populations with different glucose metabolism statuses: a cross-sectional study.Frontiers in cardiovascular medicine · 2026Article
- 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
- 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
- Negative Correlation Between Secreted Phosphoprotein 1 and the Treg/Th17 Ratio in Non-Valvular Atrial Fibrillation.Reviews in cardiovascular medicine · 2025Article
- Association between basal metabolic rate and cognitive function in Chinese older adults: the mediating effect of sarcopenia.BMC geriatrics · 2025Article
- Metabolic stress and age drive inflammation and cognitive decline in mice and humans.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
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.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.