Metabolic Dysfunction-Associated Steatotic Liver Disease Is Associated With Accelerated Brain Ageing: A Population-Based Study.
Authors
Affiliations (7)
Affiliations (7)
- Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
- Public Health Science and Engineering College, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
- Tianjin Key Laboratory of Elderly Health, Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, Tianjin, China.
- Department of Pediatric Neurosurgery, West China Second University Hospital, Sichuan University, Chengdu, China.
- Department of Health Sciences, The Swedish Red Cross University, Huddinge, Sweden.
- Department of Toxicology and Health Inspection and Quarantine, School of Public Health, Tianjin Medical University, Tianjin, China.
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to cognitive decline and dementia risk. We aimed to investigate the association between MASLD and brain ageing and explore the role of low-grade inflammation. Within the UK Biobank, 30 386 chronic neurological disorders-free participants who underwent brain magnetic resonance imaging (MRI) scans were included. Individuals were categorised into no MASLD/related SLD and MASLD/related SLD (including subtypes of MASLD, MASLD with increased alcohol intake [MetALD] and MASLD with other combined aetiology). Brain age was estimated using machine learning by 1079 brain MRI phenotypes. Brain age gap (BAG) was calculated as the difference between brain age and chronological age. Low-grade inflammation (INFLA) was calculated based on white blood cell count, platelet, neutrophil granulocyte to lymphocyte ratio and C-reactive protein. Data were analysed using linear regression and structural equation models. At baseline, 7360 (24.2%) participants had MASLD/related SLD. Compared to participants with no MASLD/related SLD, those with MASLD/related SLD had significantly larger BAG (β = 0.86, 95% CI = 0.70, 1.02), as well as those with MASLD (β = 0.59, 95% CI = 0.41, 0.77) or MetALD (β = 1.57, 95% CI = 1.31, 1.83). The association between MASLD/related SLD and larger BAG was significant across middle-aged (< 60) and older (≥ 60) adults, males and females, and APOE ɛ4 carriers and non-carriers. INFLA mediated 13.53% of the association between MASLD/related SLD and larger BAG (p < 0.001). MASLD/related SLD, as well as MASLD and MetALD, is associated with accelerated brain ageing, even among middle-aged adults and APOE ɛ4 non-carriers. Low-grade systemic inflammation may partially mediate this association.