Globally, there are 10m new cases of dementia globally each year, but, suggest scientists in a recent study, up to 13% of those in the US may have been misdiagnosed and are instead left struggling with a condition that can, in fact, be treated.
“Healthcare providers must be made aware of this potential overlap between dementia and hepatic encephalopathy, which is treatable,” said Virginia Commonwealth University hepatologist Jasmohan Bajaj.
Hepatic encephalopathy – cognitive impairment caused by liver failure – affects more than 40% of patients with advanced liver disease (cirrhosis). The brain impairments it causes are hard to distinguish from dementia.
Our livers regulate the levels of most chemicals in our bodies, from filtering them from the blood to aiding with digestion.
Aside from the well-known liver-damaging effects of alcohol, other risks to the liver include the hepatitis virus, high cholesterol, obesity and diabetes, stress, and ageing. But if caught early enough and with the right treatment, damage to our livers can be reversed.
Much of this can be mitigated through changes in diet and behaviour, and there are even more potential drug treatments on the horizon as well.
In fact, treatment of hepatic encephalopathy has resolved cognitive impairments in at least two patients who had been diagnosed with dementia.
“We’ve shown that ageing exacerbates non-alcoholic liver disease… and by reducing this impact, we can reverse the damage,” said Duke University hepatologist Anna Mae Diehl. “You are never too old to get better.”
So earlier this year, Bajaj and colleagues reviewed the medical records of 177 422 US veterans diagnosed with dementia between 2009 and 2019.
None had been diagnosed with liver disease, but the team found more than 10% had high fibrosis 4 (FIB-4) scores, an index to measure liver scarring, meaning they were very likely to have cirrhosis.
In their latest study, Virginia Commonwealth University biostatistician Scott Silvey, Bajaj, and colleagues repeated this review with 68 807 medical records of patients from a national database who aren’t veterans, to see if their earlier results reflected the general US population.
To their surprise, even more patients with high FIB-4 scores were found in this population – almost 13%.
“The prevalences and determinants of a high FIB-4 are striking, including a greater proportion of patients who were not white in the high FIB-4 group,” they said.
They added that while they did not study the specific factors behind these disparities, a lack of access to therapy or medical care in both dementia care and comorbidity care could contribute.
“This important link between dementia and liver health emphasises the importance of screening patients for potentially treatable contributors to cognitive decline,” said Bajaj.
This research was published in The American Journal of Medicine.
Study details
A possible reversible cause of cognitive impairment: undiagnosed cirrhosis and potential hepatic encephalopathy in patients with dementia
Scott Silvey, Richard Sterling, Evan French, Jasmohan Bajaj et al.
Published in The American Journal of Medicine on 26 June 2024
Abstract
Background
Dementia and hepatic encephalopathy (HE) have symptom overlap and are challenging to differentiate. The presence of undiagnosed cirrhosis may lead to missed opportunities to treat HE, which was found in a Veterans database. This needs validation in a non-veteran cohort.
Methods
A retrospective cohort study was conducted between 2009 and 2019 using national non-Veteran patient data from the multi-centre TriNetX database. Participants included 68,807 patients with a dementia diagnosis at ≥2 visits, no prior diagnosis of cirrhosis, and with sufficient laboratory test results to calculate the Fibrosis-4 (FIB-4) index, which indicates liver disease.
Prevalences of high FIB-4 scores (>2.67 and >3.25) were measured within the cohort, and associations between high FIB-4 and comorbidities/demographics were examined.
Results
Within the cohort (44.7% male, 78.0% white, mean age 72.73 years (±11.09)), 7.6% (n = 5815) had a FIB-4 index >3.25 and 12.8% (n=8683) had FIB-4 >2.67. In multivariable logistic regression models, FIB-4 > 3.25 was associated with male gender (OR: 1.42 [1.33-1.51]), congestive heart failure (OR:1.73 [1.59-1.87]), viral hepatitis (OR: 2.23 [1.84–2.68]), alcohol use disorder (OR: 1.39 [1.22–1.58]), and chronic kidney disease (OR: 1.38 [1.28–1.48]), and inversely associated with white race (OR: 0.76 [0.71–0.82]) and diabetes (OR: 0.82 [0.77–0.88]). Similar findings were associated with the FIB-4 > 2.67 threshold.
Conclusion
The findings of this national cohort suggest that the FIB-4 index could be utilised to screen for potential undiagnosed cirrhosis in patients with dementia and that hepatic encephalopathy that might be misdiagnosed as dementia or cause worsening of cognitive function in patients with dementia.
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