30-Year Study: Fatty Liver Disease Linked to 125% Surge in Dementia Risk

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30-Year Study: Fatty Liver Disease Linked to 125% Surge in Dementia Risk

30-Year Study: Fatty Liver Disease Linked to 125% Surge in Dementia Risk

Study Reveals 125% Increase in Dementia Risk for Middle-aged Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD) Related Liver Fibrosis.

A 30-year follow-up study has discovered a staggering 125% increase in the risk of dementia for middle-aged individuals with fatty liver disease!

The abnormal accumulation of beta-amyloid protein (Aβ) in the brain is a pathological characteristic of Alzheimer’s disease (AD). Aβ is not only present in the brain but also in peripheral organs, such as the liver.

Previous research has shown that Aβ produced in the liver can enter the brain, leading to neurodegeneration. Consequently, the liver and its related diseases may play a crucial role in the occurrence and development of dementia.

In a recent study, researchers from University of North Carolina explored the relationship between the severity of NAFLD-related liver fibrosis and the risk of dementia.

They found that the severity of NAFLD-related liver fibrosis in middle age is positively correlated with an increased risk of dementia. Specifically, compared to those without fatty liver, individuals with low, moderate, and high-risk liver fibrosis related to NAFLD in middle age had a 45%, 40%, and 125% increased risk of dementia, respectively (HR of 1.45, 1.40, and 2.25, all P values < 0.05).

The study was published in Alzheimer’s & Dementia.

30-Year Study: Fatty Liver Disease Linked to 125% Surge in Dementia Risk

NAFLD is one of the most common chronic liver diseases, affecting 25% of the global population. Despite numerous studies suggesting an association between NAFLD and its related liver fibrosis with the risk of dementia, population-based data has been insufficient.

To further explore the relationship between NAFLD and its related liver fibrosis and the risk of dementia, researchers selected 8,972 participants with an average age of 57 for the middle-aged NAFLD cohort (enrolled from 1990 to 1992, second follow-up of the Atherosclerosis Risk in Communities [ARIC] cohort, including those without fatty liver or with undetermined fatty liver status) and 4,938 participants with an average age of 75 for the elderly NAFLD cohort (enrolled from 2011 to 2013, fifth follow-up of the ARIC cohort, also including those without fatty liver or with undetermined fatty liver status).

Both cohorts were followed until December 31, 2019, or the occurrence of dementia events, with a maximum follow-up period of 30 years. Additionally, participants in both cohorts underwent comprehensive liver examinations at the time of enrollment to assess the severity of NAFLD.

Based on the progression and severity of NAFLD, researchers divided the study participants into five stages, namely, without fatty liver, undetermined fatty liver, low-risk liver fibrosis, moderate-risk liver fibrosis, and high-risk liver fibrosis.

The results revealed that in the middle-aged cohort, during a median follow-up of 24.5 years, there were 1,789 diagnosed cases of dementia. Multivariate analysis showed a positive correlation between the severity of NAFLD-related liver fibrosis in middle age and an increased risk of dementia.

Specifically, individuals with low, moderate, and high-risk NAFLD-related liver fibrosis in middle age had a significantly higher risk of dementia compared to those without fatty liver (HR of 1.45, 1.40, and 2.25, all P values < 0.05). This association persisted even after adjusting for cardiovascular, metabolic, and other risk factors.

Moving on to the elderly cohort, during a median follow-up of 6.3 years, there were 865 diagnosed cases of dementia. Unlike the middle-aged cohort, researchers did not find a significant positive correlation between the severity of NAFLD-related liver fibrosis in old age and an increased risk of dementia.

Lastly, considering previous studies indicating a link between normal low levels of alanine transaminase (ALT) and an increased risk of dementia, researchers explored the relationship between normal high and low ALT levels and the risk of dementia.

The study also divided ARIC participants into middle-aged and elderly cohorts, with 11,346 participants having normal ALT levels (<40 U/L) in the middle-aged cohort and 4,925 participants having normal ALT levels in the elderly cohort (follow-up start and end times consistent with the aforementioned cohorts, as detailed in the study design above).

The results showed that during a median follow-up of 24.5 years in the middle-aged cohort, there were 2,411 participants diagnosed with dementia. After adjusting for age, gender, and race, researchers found a U-shaped distribution of the correlation between ALT levels and the risk of dementia. In other words, compared to the median normal ALT level, both low and high normal ALT levels were associated with an increased risk of dementia (HR of 1.05 and 1.09, respectively). Specific ALT groupings and values are detailed in the figure above.

Interestingly, in the elderly cohort, the correlation between ALT levels and the risk of dementia also displayed a U-shaped distribution, and the correlation was even stronger. Specifically, both low and high normal ALT levels were associated with an increased risk of dementia compared to the median normal ALT level (HR of 2.03 and 1.43, respectively). This suggests that testing ALT in old age can be an important method of linking liver inflammation with dementia.

In summary, this 30-year follow-up study found a positive correlation between the severity of NAFLD-related liver fibrosis in middle age and an increased risk of dementia. The authors note that as a correlation study, the specific type of dementia in participants cannot be determined at this stage, and further research is needed to reveal the impact of liver and its related diseases on different types of dementia.