PMID- 38305614
OWN - NLM
STAT- MEDLINE
DCOM- 20240205
LR  - 20240307
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 28
IP  - 2
DP  - 2024 Jan
TI  - Role of alanine aminotransferase in the effects of urinary caffeine concentration 
      and its primary metabolite concentration on cognitive function in older adults: 
      Bayesian Kernel Machine regression analysis and mediation analysis.
PG  - 721-733
LID - 35072 [pii]
LID - 10.26355/eurrev_202401_35072 [doi]
AB  - OBJECTIVE: This study aimed to explore the role of alanine aminotransferase (ALT) 
      in the effects of urinary caffeine and its primary metabolites on cognitive 
      function in elderly people. MATERIALS AND METHODS: In this investigation, we 
      meticulously curated a cohort from the 2011-2014 National Health and Nutrition 
      Examination Survey (NHANES) database. Animal fluency emerged as the pivotal 
      metric for assessing cognitive function within our study population. In order to 
      navigate the intricacies of mixture analysis and circumvent potential 
      complexities, we harnessed the power of Bayesian kernel machine regression (BKMR) 
      models. This method allowed us to dissect the nuanced impacts of caffeine and its 
      primary urinary metabolites on cognitive function. While accounting for caffeine 
      and its metabolites, we analyzed the relationship between ALT and cognitive 
      function through non-linear dynamics. Lastly, employing structural equation 
      modeling, we probed the intriguing question of whether ALT mediates the influence 
      of 3,7-dimethylxanthine on cognitive function. This comprehensive approach has 
      unveiled a deeper understanding of the multifaceted interplay among these 
      variables, offering invaluable insights into the determinants of cognitive 
      function within our cohort. RESULTS: After meticulous adjustment for various 
      covariates, our linear regression analysis unveiled a noteworthy finding: 
      3,7-dimethylxanthine demonstrated a significant positive correlation with 
      cognitive function (p < 0.05). Importantly, within the BKMR model employed, 
      3,7-dimethylxanthine emerged as the most influential factor within the compound, 
      with posterior inclusion probabilities of 0.995 and 0.939. Furthermore, our 
      single-exposure effect model confirmed its presence at the 25th, 50th, and 75th 
      percentile concentrations of other components within the compound. Interestingly, 
      bivariate concentration curves indicated no interaction within the compound, 
      underscoring the prominent impact of 3,7-dimethylxanthine on cognitive function. 
      Subsequently, through a test of Restricted Cubic Splines (RCS), we revealed a 
      non-linear relationship between ALT and cognitive function at the 10th, 50th, and 
      90th percentiles (p < 0.05), indicating a heightened risk of diminished cognitive 
      function in the low ALT group. Employing structural equation modeling, we 
      meticulously examined the mediating role of ALT in relation to 
      3,7-dimethylxanthine and cognitive function. However, our study results did not 
      yield significant evidence of a mediating effect. This comprehensive analysis 
      elucidates the intricate interplay between these variables, unveiling the subtle 
      mechanisms governing cognitive function. CONCLUSIONS: In this study, a noteworthy 
      positive correlation was observed between 3,7-dimethylxanthine and cognitive 
      function. Additionally, a non-linear relationship was identified between ALT and 
      cognitive function, with lower levels of ALT associated with a decline in 
      cognitive function. The RCS trend suggested that higher levels of ALT may 
      similarly lead to diminished cognitive performance. However, in our pursuit to 
      ascertain potential mediation, we regrettably found no significant evidence 
      supporting mediation among these factors involving ALT. This underscores the need 
      for more comprehensive investigations and expanded clinical explorations into the 
      intricate associations among these three pivotal elements.
FAU - Qin, Y-J
AU  - Qin YJ
AD  - Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China. 2021120402@stu.cqmu.edu.cn.
FAU - Wang, Z-G
AU  - Wang ZG
FAU - Gong, J-H
AU  - Gong JH
FAU - Gong, J-P
AU  - Gong JP
FAU - Li, J-H
AU  - Li JH
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - 3G6A5W338E (Caffeine)
SB  - IM
MH  - Aged
MH  - Humans
MH  - *Alanine Transaminase/metabolism
MH  - Bayes Theorem
MH  - *Caffeine/urine
MH  - *Cognition
MH  - Mediation Analysis
MH  - Nutrition Surveys
EDAT- 2024/02/02 12:44
MHDA- 2024/02/05 06:43
CRDT- 2024/02/02 09:39
PHST- 2024/02/05 06:43 [medline]
PHST- 2024/02/02 12:44 [pubmed]
PHST- 2024/02/02 09:39 [entrez]
AID - 35072 [pii]
AID - 10.26355/eurrev_202401_35072 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2024 Jan;28(2):721-733. doi: 
      10.26355/eurrev_202401_35072.