Liver Fibrosis (assessed non-invasively) and the Risk of Incident Dementia – A Populaton-based Cohort Study with a 17-Year Follow-Up

Yochai Schonmann, Hanny Yeshua, Shira Zelber-Sagi, Galit Weinstein

Keywords: Liver fibrosis; fatty liver, FIB-4, dementia, population-based

Background:

Fatty liver is the most prevalent liver disease worldwide, with various levels of liver fibrosis found in 9% of patients. The FIB-4 index, combining age, platelet count, AST and ALT levels, has emerged as a non-invasive alternative to liver biopsy for fibrosis assessment. Recent evidence suggests a link between liver fibrosis and dementia.

Research questions:

To investigate whether liver fibrosis predicts future incident dementia

Method:

A population-based historical cohort study using routinely collected data, following all Clalit members aged 40-70 years from 2006 to 2022. We fitted Cox regression models to assess the association between liver fibrosis and subsequent incident dementia. We report crude results, as well as adjusted for age, sociodemographic characteristics (sex, ethnicity, socioeconomic status, peripherality), and baseline chronic morbidity (smoking, obesity, hyperlipidemia, IHD. Hypertension, prior CVA, carotid artery stenosis, CHF, diabetes mellitus, depression, anxiety, Parkinson's disease).

Results:

The anlysis included all 826,578 Clalit members with available data to calculate FIB-4 scores at baseline. The mean age was 53.0 years (±SD=7.8) and 59% were female. 9,497 (1.1%) participants were deemed as having fibrosis at baseline (FIB-4≥2.76), 180,114 (21.8%) were inconclusive (FIB-4=1.3-2.66) and 636,967 (78%) had no evidence of liver fibrosis (FIB-4<1.3). Over a mean follow-up of 15.4 years, there were 24,209 new dementia diagnoses. In fully adjusted models, inconclusive-range FIB-4 was associated with an increased incidence of dementia (HR=1.09, 95%CI 1.07-1.11 P<0.0001), while fibrosis-range FIB-4 score was associated with a greater risk (HR 1.18, 95%CI 1.10-1.27 P<0.0001); P for linearity <0.0001. The association was stronger among those with fibrosis aged 40-54 (HR=2.17, 95%CI 1.63-2.91, P<0001). The association remained robust through a range of subgroup and sensitivity analyses, including limiting the analysis to only the 15,205 participants with a formal NAFLD diagnosis at baseline.

Conclusions:

Liver fibrosis, as assessed non-invasively by the FIB-4 index, predicted future incident dementia, with evidence for a dose-response relationship.

Points for discussion:

What is the role of non-invasive techniques in assessing liver fibrosis?

Can dementia be prevented by treating fatty liver?

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