Association between dementia, Alzheimer's disease, and liver cancer: A Mendelian randomization analysis

Epidemiological studies have indicated an inverse association between neurodegenerative diseases and cancer. However, the relationship between liver cancer and dementia, particularly Alzheimer's disease (AD), remains underexplored.

This study aimed to determine the association between dementia, specifically AD, and liver cancer using Mendelian randomization (MR) analysis.

We conducted a bidirectional, two-sample MR analysis using publicly available genome-wide association studies data. The inverse-variance weighted method was employed as the primary analytical approach. To detect and correct for the effects of horizontal pleiotropy, we applied three complementary methods: MR Egger, weighted median, and Maximum likelihood.

The analysis indicated significant associations between dementia and a reduced risk of hepatocellular carcinoma (HCC) (OR: 0.87; 95%CI: 0.81-0.95; p < 0.001) and intrahepatic cholangiocarcinoma (ICC) (OR: 0.81; 95%CI: 0.72-0.92; p < 0.001). AD was significantly associated with a decreased risk of HCC (OR: 0.94; 95%CI: 0.88-0.99; p = 0.033), ICC (OR: 0.85; 95%CI: 0.78-0.93; p < 0.001), and combined hepatocellular-cholangiocarcinoma (CHC) (OR: 0.64; 95%CI: 0.43-0.93; p = 0.020). Conversely, inverse MR analyses indicated that ICC was associated with increased dementia risk (OR: 1.05; 95%CI: 1.01-1.09; p = 0.019) and CHC with increased AD risk (OR: 1.03; 95%CI: 1.00-1.04; p = 0.014).

This study suggests that dementia, particularly AD, is associated with a reduced risk of liver cancer. Conversely, liver cancer may be associated with a slightly increased risk of developing dementia and AD, although some observational studies have reported a lower risk of these conditions among cancer survivors.