The authors of the study published in JAMA Network Open said a significant number of patients with dementia may have undiagnosed liver disease and hepatic encephalopathy contributing to their cognitive impairment. Most importantly, their findings suggested that it’s possible their liver-related brain symptoms could be resolved with appropriate treatment.
Led by gastroenterologist Dr. Jasmohan Bajaj of the Richmond Veterans Affairs Medical Center in Virginia, the study included more than 177,000 former soldiers treated by the Veterans Health Administration over 10 years, between 2009 and 2019, who had been diagnosed with dementia in at least two clinic visits and who had never been diagnosed with any liver disorder.
Using the patients' laboratory results and other medical health records, the researchers found that up to 10 percent of their patient pool had a Fibrosis-4 (FIB-4) score – a "red flag" for early identification of patients at high risk of advanced liver fibrosis and their referral to specialized care, as explained in Diagnostics. Advanced liver fibrosis typically results in cirrhosis, liver failure and portal hypertension and often requires liver transplantation.
The researchers said: "A crucial tie between liver disease and dementia is what occurs in the brains of about 50 percent of people with cirrhosis: hepatic encephalopathy."
Hepatic encephalopathy is a silent condition
Alcohol, fatty deposits and hepatitis B and C virus infections can damage the liver where healthy cells are replaced by scar tissue (known as cirrhosis). When the damage continues over several years, the liver becomes so scarred that it can no longer detoxify the blood to remove toxins and waste, the researchers explained.
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At this point, toxins, mainly ammonia and manganese, can build up, get into the patient’s brain and interfere with brain function. This is hepatic encephalopathy (HE) moving from covert to overt, where patients could experience and exhibit changes to their cognition, mood, motor skills and even sleep – a profile that is notably similar to discernible indications of dementia, except that it’s reversible.
Once diagnosed, HE can be treated with laxatives to remove toxins produced by pathogens that accumulate in the gut, followed by antibiotic treatment to kill some of the harmful ammonia-producing bacteria. The severity of HE may even be a reason for clinicians treating the patient to recommend a liver transplant.
Bajaj said: "If a portion of their symptoms is caused by hepatic encephalopathy, which is way easier to treat than dementia, then I think we need to look at that. Part of the problem is that, for providers, telling apart patients with hepatic encephalopathy and dementia is nearly impossible in a brief appointment. There’s no quick, simple blood test that can separate one from the other. It takes additional, more labor-intensive tests to figure out if a patient has hepatic encephalopathy. The result might be misdiagnosis."
"HE can be very mild and difficult to diagnose." Symptoms can be indistinct and subtle – changes in sleep patterns or irritability. As the patient’s condition worsens, other symptoms emerge – confusion, disorientation or forgetfulness – and in its most severe form, HE can cause coma and death. (Related: 7 Conditions masquerading as dementia.)
The researchers again pointed out that NONE of the 177,422 veterans diagnosed with dementia who participated in the study had ever been diagnosed with liver cirrhosis or severe scarring of the liver.
"If we know the patient has cirrhosis, HE is easier to spot and treat. The trouble is that cirrhosis is a silent condition until it reaches very late stages when the liver starts to fail to perform its vital functions. HE is much harder to diagnose in the general population. The symptoms of change of behavior, confusion, forgetfulness and mood are also all seen in people diagnosed with dementia, including Alzheimer’s disease where deposits damage the brain causing typical symptoms of confusion and forgetfulness," researchers emphasized.
They added: "The disparity in potential undiagnosed cirrhosis in veterans with dementia, who lived in urban areas, were of Hispanic ethnicity and were not white, is an important issue. Dementia disproportionately affects Black and Hispanic veterans, and it is diagnosed later in the disease course in these populations, which has been attributed to lack of high-quality healthcare access.”
"A lack of access to healthcare services could also explain potentially underdiagnosed cirrhosis, which reiterates the need for focus on these sub-populations to accurately diagnose cirrhosis and potentially HE."
Bajaj and his co-authors wrote: "This study opens an important new avenue of research. It raises the awareness of checking for liver disease in people with general symptoms of dementia. This is likely to be a growing problem as the rates of both dementia and cirrhosis are increasing. But we still need better data to fully understand the number of people with HE incorrectly given a diagnosis of dementia and how best to identify and treat them."
Watch this video explaining how to prevent dementia and Alzheimer's disease.
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