DOI: 10.1002/alz.075245 ISSN: 1552-5260

Association of liver dysfunction with incident dementia, cognition, and brain structure

Pei‐Yang Gao, Ya‐Nan Ou, Hui‐Fu Wang, Ya‐Hui Ma, Zhi‐Bo Wang, Lan Tan, Jin‐Tai Yu
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



An association between liver dysfunction and cognitive impairment has been previously identified; however, further clarification is required due to the lack of comprehensive evidence. This study aimed to investigate the association between liver dysfunction and the risk of different types of incident dementia, cognitive function, and brain structural abnormalities.


A total of 431,754 UK Biobank participants without dementia at baseline were included between 2006 and 2010. The longitudinal associations between liver dysfunction and incident dementia were assessed using the Cox proportional hazards model, and the relationship between cognitive performance and brain structure was investigated using a linger regression model.


After 9.04 (Standard Deviation 2.61) years of follow‐up, 5,627 participants were diagnosed with all‐cause dementia, including 2,438 Alzheimer’s disease and 1,312 vascular dementia cases. We found that decreased alanine transaminase (Hazard Ratio 0.992, 95% Confidential Interval 0.989‐0.995, P<0.001) and increased aspartate aminotransferase (HR 1.006, 95% CI 1.002‐1.011, P = 0.002), increased aspartate aminotransferase to alanine transaminase ratio (HR 1.593, 95% CI 1.471‐1.724, P<0.001), increased direct bilirubin (HR 1.052, 95% CI 1.005‐1.101, P = 0.028), increased gamma‐glutamyl transpeptidase (HR 1.002, 95% CI 1.001‐1.006, P<0.001), alcoholic liver disease (HR 2.870, 95% CI 1.863‐4.420, P<0.001), fibrosis and cirrhosis of liver (HR 2.284, 95% CI 1.454‐3.588, P<0.001), and other liver disease (HR 1.433, 95% CI 1.040‐1.973, P = 0.028) were significantly associated with all‐cause dementia risk. Similar outcomes were obtained for Alzheimer’s disease and vascular dementia. Additionally, liver dysfunction was associated with poor cognition in four different cognitive tests and altered cortical and subcortical brain regions.


Our findings provide amplified evidence to suggest that liver dysfunction is associated with the risk of different types of incident dementia, and a close relationship has been identified between poor cognitive performance and altered brain structure.

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