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

Background: 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.

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

Methods: 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.

Results: 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).

Conclusions: 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.