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Diseases with abnormal HPA function predict CSF pTau but not CSF Abeta 1‐42 in the EPAD longitudinal cohort study
Author(s) -
Gregory Sarah,
Ritchie Craig W,
MuñizTerrera Graciela
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.049231
Subject(s) - medicine , anxiety , cohort , depression (economics) , body mass index , executive dysfunction , trail making test , diabetes mellitus , psychology , psychiatry , disease , endocrinology , cognition , neuropsychology , cognitive impairment , economics , macroeconomics
Background Hypothalamic‐pituitary‐adrenal axis (HPAa) dysfunction is associated with progression of cognitive decline in Alzheimer's disease (AD). HPAa abnormalities are also associated with diabetes, obesity, anxiety, depression and traumatic life events, all risk factors for AD. We hypothesised that these risk factors would be associated with AD biomarkers via a latent variable representing HPAa dysfunction. Method We recorded diabetes, obesity, anxiety, depression and body mass index (BMI) from medical history in the EPAD LCS v1500.0 dataset (n=1273). Participants completed the State Trait Anxiety Inventory (STAI), Geriatric Depression Scale (GDS) and Swedish National Aging Cohort (SNAC) life events questionnaires. AD biomarkers were CSF Ab1‐42, pTau and hippocampal volume. Covariates were selected if significantly associated with exposure and outcome variables. We used structural equation modelling to test the hypothesis. Result In the final model, the following associations were found with the HPAa dysfunction latent variable: diabetes (b= ‐0.38, p<0.05), obesity (b= 0.37, p<0.05) and life events (b= ‐0.15, p<0.05), with an increase in the latent variable associated with a decrease in pTau (b=‐0.13, p<0.05). Life events (b= 0.28, p<0.001), STAI (b= 0.17, p<0.01), GDS (b= 0.13, p<0.05) and BMI (b= ‐0.41, p<0.001) loaded onto the HPAa dysfunction latent variable, with an increase in the latent variable associated with an increase in pTau (b= 0.24, p<0.001). Diabetes (b= ‐0.23, p<0.01), obesity (b= 0.17, p<0.05), anxiety (b= 0.15, p<0.01) and life events (b= ‐0.27, p<0.01) loaded onto the HPAa dysfunction latent variable, with an increase in the latent variable associated with an increase in hippocampal volume (b= 0.25, p<0.01). There were no significant associations between the latent variable and CSF Ab1‐42. Conclusion Continuous measures of depression, anxiety, obesity and trauma are associated with increased CSF pTau via the HPAa dysfunction latent variable in the EPAD LCS v1500.0 dataset, whilst diagnostic categories with known HPAa dysfunction are associated with lower CSF pTau and increased hippocampal volume. Those scoring highly on anxiety, depression, life event scales and with a lower BMI may be a group that benefit from early intervention. Further research is important to understand why the continuous measures of disease were associated with higher AD risk compared to diagnoses.