Neuroimaging and biomarker evidence of neurodegeneration in asthma - 03/02/22
, Douglas C. Dean, PhD c, d, e, Barbara B. Bendlin, PhD f, h, Nizar N. Jarjour, MD f, Stephane Esnault, PhD f, Henrik Zetterberg, MD, PhD i, j, k, l, Amanda Heslegrave, PhD l, Michael D. Evans, MS m, Richard J. Davidson, PhD a, b, g, William W. Busse, MD fAbstract |
Background |
Epidemiologic studies have shown that Alzheimer's disease (AD) 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 (phosphorylated tau 181, p-Tau181), neurodegeneration (neurofilament light chain, NfL), and glial activation (glial fibrillary acidic protein, 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 which were robustly associated with GFAP and, to a lesser extent, 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.
Conclusions |
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. There is 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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, dementia, diffusion-weighted imaging, neurodegeneration, inflammation, GFAP, NfL
Abbreviations used : ACQ-6, AD, ATS, dMRI, DTI, EOS, FA, Feno, FEV1, GFAP, NfL, NODDI, PALM, p-Tau181, RT, T2
Plan
| This work was supported by funding from the National Heart, Lung, and Blood Institute R01 HL123284 to W.W.B. and U10HL109168 to N.N.J.; from the National Center for Complementary and Integrative Health P01 AT004952 to R.J.D.; and by a core grant to the Waisman Center from the National Institute of Child Health and Human Development U54 HD090256. H.Z. and A.H. acknowledge funding from the UK Dementia Research Institute. H.Z. is a Wallenberg Scholar. |
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| Disclosure of potential conflict of interest: N. N. Jarjour has a consulting relationship with GlaxoSmithKline, AstraZeneca, and Boehringer Ingelheim. H. Zetterberg has served at scientific advisory boards for Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, and CogRx; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, and Biogen; and is a cofounder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. W. W. Busse has a consulting relationship with GlaxoSmithKline, Novartis, AstraZeneca, Regeneron, and Sanofi. R. J. Davidson is the founder and president, and serves on the board of directors for the nonprofit organization Healthy Minds Innovations Inc. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 149 - N° 2
P. 589 - février 2022 Retour au numéro
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