Neuroimaging and biomarker evidence of neurodegeneration in asthma.

Abstract Background Epidemiological studies have shown that Alzheimer’s disease and related dementias (ADRD) are seen more frequently with asthma, especially with greater asthma severity or exacerbation frequency. Objective To examine the changes in brain structure that may underlie this phenomenon, we examined diffusion-weighted magnetic resonance imaging (dMRI) and blood-based biomarkers of AD (p-Tau181), neurodegeneration (NfL) and glial activation (GFAP). Methods dMRI data were obtained in 111 individuals with asthma, ranging in disease severity from mild to severe, and 135 healthy controls. Regression analyses were used to test the relationships between asthma severity and neuroimaging measures, as well as AD pathology, neurodegeneration and glial activation, indexed by plasma p-Tau181, NfL and GFAP respectively. Additional relationships were tested with cognitive function. Results Asthma participants had widespread and large magnitude differences in several dMRI metrics, which were indicative of neuroinflammation and neurodegeneration, and robustly associated with GFAP and to a lesser extent, with NfL. The AD biomarker p-Tau181 was only minimally associated with neuroimaging outcomes. Further, asthma severity was associated with deleterious changes in neuroimaging outcomes, which in turn, were associated with slower processing speed, a test of cognitive performance. Conclusion These data suggest that asthma, particularly when severe, is associated with characteristics of neuroinflammation and neurodegeneration and may be a potential risk factor for neural injury and cognitive dysfunction. The results suggest a need to determine how asthma may affect brain health and whether treatment directed toward characteristics of asthma associated with these risks can mitigate these effects.