Low Alanine Aminotransferase Levels in the Elderly Population: Frailty, Disability, Sarcopenia, and Reduced Survival

Vespasiani‐Gentilucci, Umberto; Vincentis, Antonio De; Ferrucci, Luigi; Bandinelli, Stefania; Incalzi, Raffaele Antonelli; Picardi, Antonio

doi:10.1093/gerona/glx126

Cited by 84 publications

(118 citation statements)

References 35 publications

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“…The present study with proper confounder adjustment confirmed the results of a previous study without confounder adjustment in terms of the association between low ALT and LOI . Moreover, the results of our study were consistent with those of previous studies of the elderly evaluating the independent association between low ALT and death . However, Le Couteur et al .…”

Section: Discussionsupporting

confidence: 92%

“…Although there was no information regarding the causes of LOI in our study, we expect that the causes of LOI were similar between our study and national statistics because of our population‐based cohort study design with a high follow‐up rate. In terms of cause‐specific death, a previous study also showed the association between low ALT and cardiovascular death, although respiratory disease death was not evaluated . We assume that low ALT is associated with LOI or death through various adverse events such as dementia, cardiovascular diseases including stroke, and respiratory disease.…”

Section: Discussionmentioning

confidence: 90%

“…Second, there were no data on vitamin B6, including PLP, to evaluate whether vitamin B6 deficiency explains the association between low ALT and LOI or death. Although a previous study adjusted for pyridoxine, one of the six common forms of vitamin B6, regarding the association between low ALT and death, PLP (an active form of vitamin B6) was not assessed . All forms of vitamin B6 including PLP need to be evaluated to investigate the mechanism linking low ALT and LOI or death in future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, studies evaluating the association of low ALT with loss of independence (LOI) are scarce, although LOI, including both physical and mental disability such as stroke and dementia, is an important outcome in the elderly. A recent study showed the association between low ALT and LOI, but it did not adjust for any confounders . Therefore, it is still unclear whether low ALT is a risk factor for LOI or death.…”

Section: Introductionmentioning

confidence: 98%

“…Previous systematic reviews have reported inconsistent results regarding the association between low ALT and death because of study participants' heterogeneity regarding variables such as age and geographical variation . Several studies focused on the elderly in order to evaluate whether low ALT was independently associated with death, but the results were also inconsistent . Moreover, studies evaluating the association of low ALT with loss of independence (LOI) are scarce, although LOI, including both physical and mental disability such as stroke and dementia, is an important outcome in the elderly.…”

Section: Introductionmentioning

confidence: 99%

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Association of low alanine aminotransferase with loss of independence or death: A 5‐year population‐based cohort study

Yamazaki

Kamitani

Matsui

et al. 2019

J of Gastro and Hepatol

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Background and Aim Alanine aminotransferase (ALT) is an important enzyme for amino acid metabolism and gluconeogenesis, and low ALT is an indicator of vitamin B6 deficiency. However, it is unknown whether individuals with low ALT are likely to develop loss of independence (LOI) or death. We investigated the association of low ALT with LOI or death in the elderly. Methods Between 2008 and 2010, 2,484 elderly individuals (≥ 65 years old) without functional dependency from the Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study were enrolled. Based on baseline ALT values, the participants were divided into the following groups: ALT < 10 (n = 73), 10–20 (n = 1,372), 20–30 (reference, n = 734), 30–40 (n = 201), and ≥ 40 (n = 104) U/L groups. LOI was defined as requiring complete support for basic activities of daily living, which is care levels 3–5 in Japanese long‐term care insurance certifications. The hazard ratios of LOI or death were estimated by Cox proportional hazard models adjusted for potential confounders. Results During the median follow‐up period of 5.75 (interquartile range 4.85–5.83) years, LOI or death occurred in 195 participants (7.85%). Compared with ALT 20–30 U/L, low ALT was associated with LOI or death (multivariable adjusted hazard ratios [95% confidence intervals]: 3.02 [1.57–5.81] and 1.55 [1.07–2.24] in ALT < 10 and 10–20 U/L groups, respectively), while high ALT was not (1.29 [0.72–2.31] and 1.49 [0.68–3.25] in ALT 30–40 and ≥ 40 U/L groups, respectively). Conclusions Clinicians should be aware of not only high ALT, indicating liver injury, but also low ALT associated with LOI or death.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Association of low alanine aminotransferase with loss of independence or death: A 5‐year population‐based cohort study

Yamazaki

Kamitani

Matsui

et al. 2019

J of Gastro and Hepatol

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Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers

et al. 2019

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Key Points Question Are liver function markers associated with cognition and the “A/T/N” (amyloid, tau, and neurodegeneration) biomarkers for Alzheimer disease? Findings In this cohort study of 1581 older adults, elevated aspartate aminotransferase to alanine aminotransferase ratios were associated with diagnosis of Alzheimer disease, poor cognition, lower cerebrospinal fluid levels of amyloid-β 1-42, increased amyloid-β deposition, higher cerebrospinal fluid levels of phosphorylated tau and total tau, and reduced brain glucose metabolism. Lower levels of alanine aminotransferase were associated with increased amyloid-β deposition, reduced brain glucose metabolism, greater brain atrophy, diagnosis of Alzheimer disease, and poor cognition. Meaning Consistent associations of serum-based liver function markers with Alzheimer disease biomarkers highlight the involvement of metabolic disturbances in the pathophysiology of Alzheimer disease.

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

Lu,

Pike,

Hoogeveen

et al. 2023

Alzheimer's & Dementia

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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.

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Low Alanine Aminotransferase Levels in the Elderly Population: Frailty, Disability, Sarcopenia, and Reduced Survival

Cited by 84 publications

References 35 publications

Association of low alanine aminotransferase with loss of independence or death: A 5‐year population‐based cohort study

Association of low alanine aminotransferase with loss of independence or death: A 5‐year population‐based cohort study

Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers

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

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