Dataset Information

Shared Metabolic Profile of Caffeine in Parkinsonian Disorders.

ABSTRACT: OBJECTIVE:The objective of this study was to determine comprehensive metabolic changes of caffeine in the serum of patients with parkinsonian disorders including Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) and to compare this with healthy control serum. METHODS:Serum levels of caffeine and its 11 downstream metabolites from independent double cohorts consisting of PD (n = 111, 160), PSP (n = 30, 19), MSA (n = 23, 17), and healthy controls (n = 43, 31) were examined by liquid chromatography-mass spectrometry. The association of each metabolite with clinical parameters and medication was investigated. Mutations in caffeine-associated genes were investigated by direct sequencing. RESULTS:A total of 9 metabolites detected in more than 50% of participants in both cohorts were decreased in 3 parkinsonian disorders compared with healthy controls without any significant association with age at sampling, sex, or disease severity (Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale motor section) in PD, and levodopa dose or levodopa equivalent dose in PSP and MSA. Of the 9 detected metabolites, 8 in PD, 5 in PSP, and 3 in MSA were significantly decreased in both cohorts even after normalizing to daily caffeine consumption. No significant genetic variations in CYP1A2 or CYP2E1 were detected when compared with controls. CONCLUSION:Serum caffeine metabolic profiles in 3 parkinsonian diseases show a high level of overlap, indicative of a common potential mechanism such as caffeine malabsorption from the small intestine, hypermetabolism, increased clearance of caffeine, and/or reduced caffeine consumption. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

SUBMITTER: Takeshige-Amano H

PROVIDER: S-EPMC7496239 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Shared Metabolic Profile of Caffeine in Parkinsonian Disorders.

Takeshige-Amano Haruka H Saiki Shinji S Fujimaki Motoki M Ueno Shin-Ichi SI Li Yuanzhe Y Hatano Taku T Ishikawa Kei-Ichi KI Oji Yutaka Y Mori Akio A Okuzumi Ayami A Tsunemi Taiji T Daida Kensuke K Ishiguro Yuta Y Imamichi Yoko Y Nanmo Hisayoshi H Nojiri Shuko S Funayama Manabu M Hattori Nobutaka N

Movement disorders : official journal of the Movement Disorder Society 20200501 8

<h4>Objective</h4>The objective of this study was to determine comprehensive metabolic changes of caffeine in the serum of patients with parkinsonian disorders including Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) and to compare this with healthy control serum.<h4>Methods</h4>Serum levels of caffeine and its 11 downstream metabolites from independent double cohorts consisting of PD (n = 111, 160), PSP (n = 30, 19), MSA (n = 23, 17), and healt ...[more]

PMID: 32357260

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Project description:Parkinsonism is a feature of several neurodegenerative disorders, including Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy. Neuroimaging studies have yielded insights into parkinsonian disorders; however, due to variability in results, the brain regions consistently implicated in these disorders remain to be characterized. The aim of this meta-analysis was to identify consistent brain abnormalities in individual parkinsonian disorders (Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy) and to investigate any shared abnormalities across disorders. A total of 44 591 studies were systematically screened following searches of two databases. A series of whole-brain activation likelihood estimation meta-analyses were performed on 132 neuroimaging studies (69 Parkinson's disease; 23 progressive supranuclear palsy; 17 corticobasal syndrome; and 23 multiple system atrophy) utilizing anatomical MRI, perfusion or metabolism PET and single-photon emission computed tomography. Meta-analyses were performed in each parkinsonian disorder within each imaging modality, as well as across all included disorders. Results in progressive supranuclear palsy and multiple system atrophy aligned with current imaging markers for diagnosis, encompassing the midbrain, and brainstem and putamen, respectively. PET imaging studies of patients with Parkinson's disease most consistently reported abnormality of the middle temporal gyrus. No significant clusters were identified in corticobasal syndrome. When examining abnormalities shared across all four disorders, the caudate was consistently reported in MRI studies, whilst the thalamus, inferior frontal gyrus and middle temporal gyri were commonly implicated by PET. To our knowledge, this is the largest meta-analysis of neuroimaging studies in parkinsonian disorders and the first to characterize brain regions implicated across parkinsonian disorders.

Project description:ImportanceBiomarkers of lipid, apolipoprotein, and carbohydrate metabolism have been previously suggested to be associated with the risk for depression, anxiety, and stress-related disorders, but results are inconsistent.ObjectiveTo examine whether the biomarkers of carbohydrate, lipid, and apolipoprotein metabolism are associated with the risk of depression, anxiety, and stress-related disorders.Design, setting, and participantsThis population-based cohort study with longitudinal data collection assessed 211 200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort who underwent occupational health screening between January 1, 1985, and December 31, 1996, mainly in the Stockholm region in Sweden. Statistical analysis was performed during 2022 to 2023.ExposuresLipid, apolipoprotein, and carbohydrate biomarkers measured in blood.Main outcomes and measuresThe associations between biomarker levels and the risk of developing depression, anxiety, and stress-related disorders through the end of 2020 were examined using Cox proportional hazards regression models. In addition, nested case-control analyses were conducted within the cohort, including all incident cases of depression, anxiety, and stress-related disorders, and up to 10 control individuals per case who were individually matched to the case by year of birth, sex, and year of enrollment to the AMORIS cohort, using incidence density sampling. Population trajectories were used to illustrate the temporal trends in biomarker levels for cases and controls.ResultsA total of 211 200 individuals (mean [SD] age at first biomarker measurement, 42.1 [12.6] years; 122 535 [58.0%] male; 188 895 [89.4%] born in Sweden) participated in the study. During a mean (SD) follow-up of 21.0 (6.7) years, a total of 16 256 individuals were diagnosed with depression, anxiety, or stress-related disorders. High levels of glucose (hazard ratio [HR], 1.30; 95% CI, 1.20-1.41) and triglycerides (HR, 1.15; 95% CI, 1.10-1.20) were associated with an increased subsequent risk of all tested psychiatric disorders, whereas high levels of high-density lipoprotein (HR, 0.88; 95% CI, 0.80-0.97) were associated with a reduced risk. These results were similar for male and female participants as well as for all tested disorders. The nested case-control analyses demonstrated that patients with depression, anxiety, or stress-related disorders had higher levels of glucose, triglycerides, and total cholesterol during the 20 years preceding diagnosis, as well as higher levels of apolipoprotein A-I and apolipoprotein B during the 10 years preceding diagnosis, compared with control participants.Conclusions and relevanceIn this cohort study of more than 200 000 participants, high levels of glucose and triglycerides and low levels of high-density lipoprotein were associated with future risk of depression, anxiety, and stress-related disorders. These findings may support closer follow-up of individuals with metabolic dysregulations for the prevention and diagnosis of psychiatric disorders.

Dataset Information

Shared Metabolic Profile of Caffeine in Parkinsonian Disorders.

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Shared Metabolic Profile of Caffeine in Parkinsonian Disorders.

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