Identification of plasma metabolites associated with modifiable risk factors and endophenotypes reflecting Alzheimer ’s disease pathology

This study aims to identify plasma metabolites associated with modifiable factors for AD, including MIND diet, physical activity, smoking, and caffeine intake, and tes t their association with AD endophenotypes to identify their potential roles in pathophysiological mechanisms. The association between each of the 757 plasma metabolites and four modifiable factors was tested in the wisconsin registry for Alzheimer’s prevention cohort of initially cognitively unim paired, asymptomatic middle-aged adults. After Bonferroni correction, the significant plasma metabolites were tested for association with each of the AD endophenotypes, including twelve cerebrospinal fluid (CSF) biomarkers, reflecting key pathophysiologies for AD, and four cognitive composite score s. Finally, causal mediation analyses were conducted to evaluate possible mediation effects. Analyses were performed using linear mixed-effects regression. A total of 27, 3, 23, and 24 metabolites were associated with MIND diet, physical activity, smoking, and caffeine intake, respectively. Potentia l mediation effects include beta-cryptoxanthin in the association between MIND diet and preclinical Alzheimer cognitive composite score, hippurate between MIND diet and immediate learning, glutamate between physical activity and CSF neurofilament light, and beta-cryptoxanthin between smoking and imm ediate learning. Our study identified several plasma metabolites that are associated with modifiable factors. These metabolites ...
Source: European Journal of Epidemiology - Category: Epidemiology Source Type: research