Higher baseline CSF cortisol is associated with adverse 24-month tau-related, neuroimaging, and cognitive outcomes across the Alzheimer's disease continuum.

Authors

Nahlah Fahad Alreshidi, Abdulaziz Abdullah Alghamdi, Kholoud S Almasoudi, Iman M Mirza, Sahar Abduljawad, Soha S Zakaria, Saud S Alharbi, Alzheimer’s Disease Neuroimaging Initiative

Published in

European geriatric medicine. Jul 28, 2026. Epub Jul 28, 2026.

Abstract

Cortisol dysregulation has been implicated in Alzheimer's disease (AD), but its associations with amyloid and tau-related outcomes remain unclear. This study examined whether baseline CSF cortisol was associated with cross-sectional and baseline-adjusted 24-month multimodal AD biomarkers and cognitive outcomes.
A total of 764 participants were included, comprising cognitively normal (CN; n = 284), individuals with mild cognitive impairment (MCI; n = 356), and patients with AD dementia (n = 124). Associations between baseline CSF cortisol, multimodal AD biomarkers, and cognitive outcomes were assessed with FDR correction.
CSF cortisol increased modestly from CN to MCI and AD dementia, with a small but statistically significant overall group difference after FDR correction. Cross-sectionally, in the MCI group, higher CSF cortisol was associated with higher CSF total tau and p-tau181 and a lower Aβ42/total tau ratio. In baseline-adjusted 24-month analyses, in MCI groups, higher CSF was associated with higher CSF total tau and p-tau181, greater temporal tau-PET burden, lower hippocampal volume, greater ventricular volume, and poorer cognitive outcomes. In the full cohort and MCI group, CSF-defined amyloid positivity strengthened associations of higher baseline CSF cortisol with adverse 24-month tau-related outcomes. Exploratory analyses suggested that 24-month CSF total tau and hippocampal volume partly accounted for the association between higher baseline CSF cortisol and poorer 24-month cognition in MCI; however, these findings do not establish causal mediation.
Higher CSF cortisol may be linked to tau-related pathology and poorer cognition, supporting further evaluation of its prognostic value across the AD continuum.

PMID:
42518151
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.

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