Fatty Liver Disease Not Linked to Increased Risk of Parkinson’s

No higher disease risk found for men or women in new study

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by Andrea Lobo |

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Fatty liver disease may not be among the risk factors for Parkinson’s in either men or women, according to a study in the Netherlands involving older people with liver problems.

The new study found no link to an increased risk of the neurodegenerative disorder in this elderly European population.

The findings challenge those previously reported in Korea and Israel, which suggested an increased risk of Parkinson’s in people with fatty liver disease. These inconsistencies may be due to distinct methodology and age groups, as well as the involvement of patients from different ethnic groups, the researchers noted.

The team said their results “may … be more representative of the entire Caucasian fatty liver disease population.”

The study, “Sex-stratified associations between fatty liver disease and Parkinson’s disease: The Rotterdam study,” was published in the form of a correspondence in the journal Parkinsonism & Related Disorders.

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Looking for links to fatty liver disease

“Fatty liver disease is the most common chronic liver disease, with an estimated global prevalence of 33% in 2019,” the researchers wrote. It is caused by the storage of extra fat in the liver, reaching 5–10% of the liver weight.

While the majority of people with fatty liver disease do not experience symptoms, the condition is associated with a range of complications in both the liver and outside the liver.

Previous studies have suggested an association between liver disease and Parkinson’s.

A large-scale Korean study, published in 2020, found that elevated blood levels of the liver enzyme gamma-glutamyltransferase (GGT) — a marker of liver disease — were associated with a higher risk for Parkinson’s disease in women and a lower risk in men.

Another Korean study reported that fatty liver disease increased the risk of developing Parkinson’s in women and decreased the risk in men. Meanwhile, a study in Israel found an increased Parkinson’s risk among both men and women with fatty liver disease and active inflammation.

“Considering the limited and conflicting evidence on the association between fatty liver disease and PD, we investigated this association within the ongoing Rotterdam Study,” the researchers wrote.

The Rotterdam Study, launched in 1990 in the Netherlands and involving patients ages 45 and older, now boasts more than 15,000 participants. It aims to unravel the causes, preclinical course, natural history, and potential targets for intervention of chronic diseases in mid- and late-life.

Here, a team of researchers at Erasmus MC University Medical Center, in Rotterdam, analyzed demographic and clinical data from 8,848 participants who visited the study center between 1997 and 2008 and had data on liver disease.

The study’s starting, or baseline data was set on the date of liver assessment; follow-up ended at the diagnosis of Parkinsonism, Parkinson’s, time of death, loss to follow-up, or January 1, 2018. Parkinsonism refers to a group of neurological disorders that cause movement problems similar to those seen with Parkinson’s.

At baseline, the participants’ mean age was 64.7, and 43.7% were men. More than half (69.4%) were smokers.

The presence of fatty liver disease was defined by a fatty liver index (FTI) of 60 or higher for Caucasian populations. The FTI is an algorithm comprising body mass index, waist circumference, GGT levels, and the levels of triglycerides, a type of fat in the blood.

Between 2009 and 2014, 5,526 participants also underwent abdominal ultrasound, which is a more accurate method to detect fatty liver disease.

Two largely overlapping types of fatty liver disease were considered: metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty liver disease (NAFLD).

MAFLD is classified as fatty liver disease together with either being overweight, diabetes, or two minor metabolic dysfunctions. NAFLD is defined in the absence of excessive alcohol consumption, viral hepatitis, or use of medications that cause fat accumulation.

Results showed that the participants’ mean FLI was 48.2, with 35.9% of them presenting an FLI consistent with fatty liver disease. The prevalence of MAFLD was 35.8%: 45.5% in women and 28.3% in men, in alignment with the expected prevalence in Europe.

The frequency of NAFLD was 34.1%.

Over a median of 11 years of follow-up, 159 participants developed parkinsonism and 74 Parkinson’s disease. No type of fatty liver disease was associated with the conditions, both in men and women.

Notably, “results were consistent either using NAFLD or MAFLD … defined by either FLI or ultrasound,” the researchers wrote.

Although the results were different from those reported in the previous Korean study, the team noted that the FLI cut-off values used to define fatty liver disease differed between the two studies, which could influence the results. In part, the difference “could be partly explained by FLI applicability in Asian people,” they wrote.

In addition, the Korean study included younger participants (mean age 54–55 years), in whom Parkinson’s development may not be as common.

“Our study populations’ age might be highly suitable to investigate associations between PD and NAFLD,” the team wrote, adding that when the Korean study focused on people with 65 years or older, in whom Parkinson’s is more common, “the sex differences in the association between fatty liver disease and PD disappeared.”

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