Associations among plasma, MRI and amyloid PET biomarkers of dementia and the impact of health‐related comorbidities

Abstract

AbstractBackgroundKnowledge regarding associations between plasma and neuroimaging biomarkers indexing neurodegeneration and neuropathology observed in dementia is limited. Further, it is uncertain how comorbid health complications (e.g., kidney function) may alter plasma levels and impact associations with neuroimaging biomarkers.MethodWe examined associations between plasma and neuroimaging biomarkers in cognitively normal participants (NC; N = 300) and individuals with consensus diagnosis (Dx) of mild cognitive impairment (MCI; N = 192) or dementia (DEM; N = 64) enrolled in the Wake Forest ADRC (Table 1). We examined plasma biomarkers (Quanterix SIMOA HD‐X: Aβ42/40, GFAP, NfL, p‐tau181) and neuroimaging measures of amyloid deposition (global PiB PET SUVr; Aβ‐PET), total brain volume (BVOL), global white matter hyperintensity volume (WMH), diffusion‐weighted fractional anisotropy (FA) and NODDI freewater (FW; white matter). Linear models adjusted for APOE‐ε4 carrier status, demographics (age, sex, race, education), and cardiometabolic factors (estimated glomerular filtration rate (eGFR); BMI).ResultsPlasma biomarkers were moderately correlated with each other (absolute r = .22‐.64; all p<.001) and significantly elevated (Aβ42/40 lower) in DEM and MCI (Figure 1) versus NC, and Aβ‐PET‐positive (SUVr >1.21) versus negative individuals (all p<.001). Plasma and neuroimaging markers were significantly associated in both unadjusted models and models including eGFR and BMI (all p<.05; attenuation effect <10% with and without Dx; Figure 2a & 2b). In fully adjusted models (Figure 2b: Dx and all covariates), age, sex, and race differentially impacted associations of Aβ42/40, p‐tau181, and NfL with neuroimaging biomarkers (coefficients p <.05). APOE‐ε4 status exclusively impacted associations with Aβ‐PET SUVr/status. GFAP remained significantly associated with all neuroimaging biomarkers after covariate adjustment; no Aβ42/40 associations survived adjustment. P‐tau181 remained significantly associated with Aβ‐PET and BVOL, while associations with NfL were reduced in models stratified by Dx.ConclusionAmong aging community‐dwelling participants, plasma biomarkers significantly differed between diagnostic groups (DEM>MCI>NC), were elevated in Aβ‐PET positive individuals, and associated with poorer brain health. Except for GFAP, and to an extent p‐tau181, associations between plasma and neuroimaging biomarkers were differentially impacted by inclusion of comorbidities and covariates when stratified by diagnosis. Future work will examine high‐dimensional interactions among comorbidities, demographic information, and plasma and neuroimaging biomarkers in individuals with or at‐risk of dementia.