Diseases with abnormal HPA function predict CSF pTau but not CSF Abeta 1‐42 in the EPAD longitudinal cohort study

Abstract Background Hypothalamic‐pituitary‐adrenal axis (HPAa) dysfunction is associated with progression of cognitive decline in Alzheimer's disease (AD). HPAa abnormalities are also diabetes, obesity, anxiety, depression and traumatic life events, all risk factors for AD. We hypothesised that these would be AD biomarkers via a latent variable representing dysfunction. Method recorded body mass index (BMI) from medical history the EPAD LCS v1500.0 dataset (n=1273). Participants completed State Trait Anxiety Inventory (STAI), Geriatric Depression Scale (GDS) Swedish National Aging Cohort (SNAC) events questionnaires. were CSF Ab1‐42, pTau hippocampal volume. Covariates selected if significantly exposure outcome variables. used structural equation modelling to test hypothesis. Result In final model, following associations found variable: diabetes (b= ‐0.38, p<0.05), obesity 0.37, p<0.05) ‐0.15, an increase decrease (b=‐0.13, p<0.05). Life 0.28, p<0.001), STAI 0.17, p<0.01), GDS 0.13, BMI ‐0.41, p<0.001) loaded onto variable, 0.24, p<0.001). Diabetes ‐0.23, anxiety 0.15, p<0.01) ‐0.27, volume 0.25, p<0.01). There no significant between Ab1‐42. Conclusion Continuous measures depression, trauma increased dataset, whilst diagnostic categories known lower Those scoring highly on event scales may group benefit early intervention. Further research important understand why continuous higher compared diagnoses.