Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health‐related comorbidities in a community‐dwelling cohort

INTRODUCTION We evaluated associations between plasma and neuroimaging‐derived biomarkers of Alzheimer's disease and related dementias and the impact of health‐related comorbidities. METHODS We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aβ] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aβ‐positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion‐weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N = 299), mild cognitive impairment (MCI; N = 192), or dementia (DEM; N = 65). Biomarkers were compared across groups stratified by diagnosis, sex, race, and APOE ε4 carrier status. General linear models examined plasma‐imaging associations before and after adjusting for demographics (age, sex, race, education), APOE ε4 status, medications, diagnosis, and other factors (estimated glomerular filtration rate [eGFR], body mass index [BMI]). RESULTS Plasma biomarkers differed across diagnostic groups (DEM > MCI > CU), were altered in Aβ‐PET‐positive individuals, and were associated with poorer brain health and kidney function. DISCUSSION eGFR and BMI did not substantially impact associations between plasma and neuroimaging biomarkers. Highlights Plasma biomarkers differ across diagnostic groups (DEM > MCI > CU) and are altered in Aβ‐PET‐positive individuals. Altered plasma biomarker levels are associated with poorer brain health and kidney function. Plasma and neuroimaging biomarker associations are largely independent of comorbidities.