Medical textbooks tell that there are many subtypes of dementia:
- Alzheimer's disease
- Lewy bodies
- Parkinson's disease
- Huntington's disease
- Creutzfeldt-Jakob disease
These well delineated classifications are based on molecular characteristics of certain proteins aggregates and often scientists do not agree with their peers which protein causes which disease.
In general there is no recognized biomarkers for such diseases which tells a lot about the confidence biologists have in their own art.
In addition it is clear from clinical trials that the idea that dementia are caused by protein clumps, are useless to design effective drugs.
There is growing recognition of the role of chronic liver disease in brain health, but the impact of liver fibrosis on dementia risk was unclear.
The liver is a major organ which supports almost every other organ in the body. It performs near 500 essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth.
The liver produces the enzyme catalase to break down hydrogen peroxide, a toxic oxidising agent, into water and oxygen. Indeed oxidation plays an important role in aging and neurodegenerative diseases. The oxidative capacity of the liver decreases with aging.
Scientists in this pre-print describe how they evaluated the association between liver fibrosis and incident dementia using data from a large prospective cohort study.
They performed a cohort analysis using data from the UK Biobank study, which prospectively enrolled approximately 500,000 adults starting 2007 and continues to follow them. Liver fibrosis was defined using validated cutoffs of the Fibrosis-4 (FIB-4) liver fibrosis score.
The FIB-4 Index is a blood-based diagnostic test that looks at underlying fibrosis that can be used as a measure to help determine NAFLD/NASH status. While originally developed to detect liver fibrosis among patients with Hepatitis C and HIV, FIB-4 scoring has been increasingly used by the diabetes and NAFLD/NASH. The FIB-4 scoring system is determined from the values of patient age, platelet count, aspartate aminotransferase (AST), and alanine aminotransferase (ALT).
The primary outcome was incident dementia, ascertained using a validated approach based on participants hospital record and mortality data. Secondary outcomes were Alzheimers disease and vascular dementia. The scientists here excluded participants with prevalent dementia.
The scientists evaluated the association between liver fibrosis and incident dementia while adjusting for potential confounders. Prespecified interaction analyses tested for effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status. Among 455,226 participants included in this analysis, the mean age was 56.5 years and 54% were women. Standard liver chemistries were largely in the normal range.
However, 2.17% had liver fibrosis based on their FIB-4 score. In this subset, the rate of dementia per 1,000 person-years was 1.76 in participants with liver fibrosis while the rate of dementia was 0.52 in those without liver fibrosis. So this provides a clear indication that liver diseases are somehow associated with dementia.
Many confounding factors could exist so after adjusting for demographics, socioeconomic deprivation, educational attainment, metabolic syndrome, hypertension, diabetes, dyslipidemia, tobacco and alcohol use, the scientists found that liver fibrosis was still associated with an increased risk of dementia.
The classic symptoms of liver damage include the following:
Pale stools occur when stercobilin, a brown pigment, is absent from the stool. Stercobilin is derived from bilirubin metabolites produced in the liver. Dark urine occurs when bilirubin mixes with urine Jaundice (yellow skin and/or whites of the eyes) This is where bilirubin deposits in skin, causing an intense itch. Itching is the most common complaint by people who have liver failure. Often this itch cannot be relieved by drugs.