Liver integrity and the risk of Alzheimer's disease and related dementias

Abstract

INTRODUCTIONWe examined midlife (1990–1992, mean age 57) and late‐life (2011–2013, mean age 75) nonalcoholic fatty liver disease (NAFLD) and aminotransferase with incident dementia risk through 2019 in the Atherosclerosis Risk in Communities (ARIC) Study.METHODSWe characterized NAFLD using the fatty liver index and fibrosis‐4, and we categorized aminotransferase using the optimal equal‐hazard ratio (HR) approach. We estimated HRs for incident dementia ascertained from multiple data sources.RESULTSAdjusted for demographics, alcohol consumption, and kidney function, individuals with low, intermediate, and high liver fibrosis in midlife (HRs: 1.45, 1.40, and 2.25, respectively), but not at older age, had higher dementia risks than individuals without fatty liver. A U‐shaped association was observed for alanine aminotransferase with dementia risk, which was more pronounced in late‐life assessment.DISCUSSIONOur findings highlight dementia burden in high‐prevalent NAFLD and the important feature of late‐life aminotransaminase as a surrogate biomarker linking liver hypometabolism to dementia.Highlights Although evidence of liver involvement in dementia development has been documented in animal studies, the evidence in humans is limited. Midlife NAFLD raised dementia risk proportionate to severity. Late‐life NAFLD was not associated with a high risk of dementia. Low alanine aminotransferase was associated with an elevated dementia risk, especially when measured in late life.

Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

“…Recent studies propose that the liver impacts the risk and progression of neurodegenerative disorders [ 16 , 17 , 18 , 19 ]. As the peripheral organs and the central nervous system (CNS) bidirectionally communicate, changes in one can influence the other.…”

Editorial: Health conditions outside the brain and the risk of brain aging and dementia

“…Indeed, the Lancet Commission on dementia prevention, intervention, and care includes hypertension, obesity, diabetes and hearing loss among 12 modifiable risk factors that account for around 40% of dementia globally (Livingston et al, 2020 ). However, many other health conditions outside the brain may contribute to neuropathology, cognitive impairment and dementia, including non-alcoholic fatty liver disease (Lu et al, 2023 ), kidney disease (Drew et al, 2019 ), and sarcopenia (Maniscalco et al, 2024 ). Further investigation is needed to determine whether these and other conditions are independent risk factors for brain aging and dementia, and when during the lifespan they exert their greatest effect.…”