Faster cognitive declines seen in patients at risk of liver scarring

Liver fibrosis may be 'unrecognized determinant' in Parkinson's: Analysis

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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People with Parkinson’s disease at a higher risk of liver scarring, known as fibrosis, experienced faster cognitive declines compared with patients at a lower risk, according to a new analysis.

In fact, over a five-year period, liver scarring was tied to a “more rapid decline in scores” across four commonly used cognitive assessment tests, the data showed.

“Liver fibrosis may be an unrecognized determinant of cognitive outcomes in people with PD [Parkinson’s],” the researchers wrote.

“Further work is required to uncover underlying mechanisms and develop and test liver-targeted strategies to preserve cognitive health in PD,” they added.

The study, “Association of liver fibrosis with cognitive decline in Parkinson’s disease,” was published in the Journal of Clinical Neuroscience.

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Investigating the impact of liver scarring on cognition in Parkinson’s patients

Cognitive dysfunction — slowed thinking, attention difficulties, and problems remembering, among other symptoms — is common in Parkinson’s disease, and can range from mild impairments to dementia. In patients with dementia, cognitive problems can interfere significantly with daily functioning.

Increasing evidence indicates that systemic factors throughout the body, such as cardiovascular disease and blood sugar, can influence Parkinson’s risk and progression, according to the authors.

Liver dysfunction has been been proposed as a risk factor for cognitive impairment and dementia in the general population, but “little is known about the impact of liver health on the course of [Parkinson’s disease],” the researchers wrote.

To learn more, a team from Weill Cornell Medicine, in New York, explored the relationship between cognitive performance in Parkinson’s and liver fibrosis — the excessive buildup of scar tissue in the liver that is seen in most types of chronic liver disease.

Data from the global Parkinson’s Progression Markers Initiative (PPMI) study were retrospectively reviewed. In PPMI, a study by The Michael J. Fox Foundation for Parkinson’s Research, long-term clinical, MRI, genetic, and other data are collected from people with the neurodegenerative disorder, as well as from at-risk and healthy individuals.

A total of 409 Parkinson’s patients who had liver health data available were included in the analysis. Cognitive performance was assessed annually over a five-year period.

The patients, of whom 40% were women, had a mean age of 60.8. Most (93%) were within five years of their Parkinson’s diagnosis. Five people had a clinical history of liver conditions, and no patients had a diagnosis of cognitive impairment or dementia.

The probability that a person had liver fibrosis was assessed by FIB-4 scores, a calculation that takes into account age, liver enzyme levels in the blood, and the individual’s number of platelets, which are blood cell fragments involved in clotting that are altered in many liver diseases.

Among the patients, the median FIB-4 score was 1.2 — any score of 1.3 or higher was considered to be associated with an intermediate to high probability of liver fibrosis.

A total of 179 people met that criteria.

The clinical characteristics between those at intermediate/high fibrosis risk and those at a low risk were generally similar, but the higher risk group was significantly older.

While patients in the intermediate/high risk group did have significantly altered liver enzyme and platelet levels compared with low risk individuals, these markers were still in the normal range in both groups. That likely indicates that any liver impairments were subclinical even in the high risk group, according to the authors.

“Even in participants with FIB-4 [greater than or equal to] 1.3, liver chemistries were overwhelmingly within the normal range,” the researchers wrote.

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Greater cognitive function decline seen over 5 years in high-risk patients

In the final statistical analyses, starting cognitive function between the two groups was not significantly different, as assessed by the Montreal Cognitive Assessment (MoCA) and a battery of other tests.

While the change in MoCA scores over time was small for both groups, they declined more rapidly among patients in the higher risk group, who experienced an average 0.09-point decrease in their MoCA score every six months. The average decline in the low risk group was 0.01 points.

Similar findings were observed across several other tests designed to evaluate various domains of cognitive function.

According to the researchers, that data suggest “that clinically subtle or covert liver fibrosis may be associated with cognitive worsening in PD.”

Still, only one person developed a diagnosis of mild cognitive impairment over the course of follow-up. The team noted that, “with more follow-up, differences in the rates of the clinical diagnosis of mild cognitive impairment or dementia may emerge.”

Altogether, “our findings suggest that subclinical liver fibrosis may broadly impact cognitive performance over time,” the researchers wrote.

“Liver fibrosis may therefore be an additional systemic factor… that impacts the clinical course of PD,” they wrote.

Mechanistically, it is possible that damage to the liver reduces its ability to help clear toxic substances from the body, exacerbating the accumulation of neurotoxic proteins that drive nerve cell death, the team hypothesized.

Our findings suggest that subclinical liver fibrosis may broadly impact cognitive performance over time. … Liver fibrosis may therefore be an additional systemic factor… that impacts the clinical course of [Parkinson’s].

More research is needed to understand these mechanisms and confirm the observed relationships, particularly with a more direct measure of liver fibrosis and more diverse study populations, the team said. Also, the role of alcohol consumption, which influences liver health, must be more thoroughly accounted for, they noted.

“Further work is required to … understand whether liver fibrosis worsens cognitive outcomes in PD through global mechanisms, mechanisms specific to PD, or other neurodegenerative mechanisms such as those seen in Alzheimer’s disease,” the researchers wrote wrote.

Meanwhile, the team suggested proactive measures may be helpful for people with Parkinson’s who may be at risk.

“Counseling patients with PD to preserve liver health through the avoidance of excess alcohol use and mitigation of nonalcoholic fatty liver disease may be reasonable,” the researchers wrote.