Influence of lung function on macro‐ and micro‐structural brain changes in mid‐ and late‐ life: a large population‐based cohort study in the UK Biobank

Abstract

AbstractBackgroundLung function has been associated with cognitive decline and dementia, but the extent to which lung function impacts brain structural changes remains unclear. We aimed to investigate the association of lung function with structural macro‐ and micro‐ brain changes across mid‐ and late‐ life in a large population‐based cohort study.MethodThe study included a total of 37,590 neurologic disorder‐free participants aged 40‐70 years from the UK Biobank, who underwent brain magnetic resonance imaging (MRI) scans 9 years after baseline. After 2.5 years, a subsample (n = 3,941) underwent a second MRI scan. Lung function was assessed using a composite score based on forced expiratory volume in 1 second, forced vital capacity, and peak expiratory flow, and divided into tertiles (i.e., low, moderate, and high). Regional brain volumes (including total brain, gray matter, white matter, hippocampus, and white matter hyperintensities) and diffusion markers (fractional anisotropy [FA] and mean diffusivity [MD]) were assessed. Data were analyzed using linear regression and mixed‐effects models.ResultAt baseline, lung function ranged from ‐3.43 to 22.91 among all participants. In multi‐adjusted linear regression, low lung function was dose‐dependently related to smaller brain volumes and lower white matter integrity. Compared to high lung function, low lung function was associated with smaller total brain (β [95% CI]: ‐0.083 [‐0.097, ‐0.070], gray matter ‐0.145 [‐0.161, ‐0.130], white matter ‐0.017 [‐0.031, ‐0.004], and hippocampal ‐0.102 [‐0.128, ‐0.075]) volume, as well as poor white matter health (FA ‐0.165 [‐0.195, ‐0.135] for lower, WMH 0.269 [0.242, 0.295] and MD 0.168 [0.140, 0.196] for higher). Over the 2.5 years follow‐up, low PF was associated with reduced white matter (‐0.021 [‐0.041, ‐0.002]) and hippocampal (‐0.078 [‐0.110, ‐0.046]) volume, reduced FA (‐0.063 [‐0.091, ‐0.035]), and increased WMH volume (0.065 [0.016, 0.114]) and MD (0.121 [0.089, 0.154]). After stratification by age, the associations remained significant among adults aged 40‐60 years and 60+ years.ConclusionLow lung function is associated with macro‐ and micro‐ structural brain changes involving both neurodegenerative and vascular pathologies. This association is significant in both mid‐ and late‐ life.