ReviewFrontiers in aging neuroscience2026
Chronic stress, cortisol dysregulation, and neurodegenerative vulnerability: mechanistic pathways linking HPA-axis dysfunction to Alzheimer's disease risk.
Review in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic psychological stress is increasingly recognized as a silent risk factor of long-term brain vulnerability and a potential modifier of neurodegenerative disease trajectories. The persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis and the consequent dysregulation of cortisol exert extensive influences on neural, immune, and metabolic pathways linked to cognitive decline and dementia. This review synthesizes current mechanistic and clinical evidence concerning the effects of chronic stress-induced HPA-axis dysfunction on neurodegenerative susceptibility and Alzheimer's disease risk. A structured narrative synthesis was conducted using literature from PubMed/MEDLINE, Scopus, and Web of Science, integrating multidisciplinary evidence from established biological and mechanistic domains. Present evidence suggests that prolonged exposure to glucocorticoids is associated with structural and functional alterations in the brain, including hippocampal atrophy, prefrontal cortical dysfunction, reduced synaptic plasticity, and increased amygdala activity. Chronic dysregulation of cortisol may result in neuroinflammation, disruption of the blood-brain barrier, induce mitochondrial dysfunction, and impair neuronal integrity. These interconnected mechanisms contribute to amyloid accumulation, tau pathology, and the progressive decline of neural resilience. Rather than serving as the root cause, chronic psychological stress can increase the likelihood of neurodegeneration by triggering complex interactions between the neuroendocrine and neuroimmune systems that accelerate the already existing pathological pathways toward neurodegeneration. Recognizing chronic stress as a potentially modifiable biological risk factor may improve early risk stratification and identification of HPA-axis dysregulation, ultimately driving preventive strategies targeting stress-related neurobiological pathways.
Indexed as
Identifiers
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.