Aging
The interplay of air pollution with plasma neurodegenerative markers and metabolome for dementia, Parkinson’s Disease and all-cause mortality risks and transitions: the UK Biobank study May A. Beydoun* May Beydoun Tianyi Huang Yi-Han Hu Jordan Weiss Michael F. Georgescu Nicole Noren Hooten Marie T. Fanelli-Kuczmarski Hind A. Beydoun Minkyo Song Lenore J. Launer Michele K. Evans Alan B. Zonderman
Interactions between two important neurodegeneration exposures [Neurofilament Light (NfL), and Glial Fibrillary Acidic Protein (GFAP)], air pollution and the plasma metabolome, in relation to transitions from healthy to neurodegenerative phenotypes [dementia, Parkinson’s Disease (PD)] and mortality were examined. Data were extracted from 19,645 UK Biobank participants (mean baseline age=61y, follow-up:2006-2023). Parametric Weibull models were conducted within a multistate framework, including two-way interactions among three groups of exposures (i.e. NfL/GFAP, air pollution and plasma metabolome). Healthy–>PD; Healthy–>Dementia; and Healthy–>Death transitions were directly associated with elevated NfL, while only Healthy–>Dementia was positively and strongly linked to elevated GFAP (fully-adjusted hazard ratio, above vs. below median GFAP, HR=2.65, 95% CI: 2.17-3.25, PDeath transition, while nitric oxide exposures (NO2 and NOx) attenuated the association between GFAP for this same transition. Synergism between PM2.5 and several metabolomic clusters was detected for Healthy–>Dementia and Healthy–>PD transitions, pertaining mainly to cholesteryl esters in very low-density lipoproteins (VLDL) for dementia, cholesterol/cholesteryl esters in chylomicrons/extremely large VLDL, and acetone/acetoacetate/3-hydroxybutyrate for PD. Metabolomic markers also interacted with NfL/GFAP to increase Healthy–>mortality and Healthy–>dementia transition risk, while branched-chain amino acids and omega-3 fatty acids as main effects were among metabolites to be inversely related to Healthy–>dementia transition. In conclusion, NfL and GFAP consistently predicted dementia risk, while air pollution modified their associations with mortality risk. The metabolome interacted with neurodegenerative and air pollution markers, including PM2.5, in relation to PD, dementia and mortality risk.
