Dataset Information

The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein ?4 Allele Variant in Patients With Dementia.

ABSTRACT: Background:The apolipoprotein E ?4 gene variant (APOE?4) confers considerable risk for dementia and affects neuroinflammation, brain metabolism, and synaptic function. The kynurenine pathway (KP) gives rise to neuroactive metabolites, which have inflammatory, redox, and excitotoxic effects in the brain. Aim:To assess whether the presence of at least one APOE?4 allele modifies the association between kynurenines and the cognitive prognosis. Methods:A total of 152 patients with sera for metabolite measurements and APOE genotype were included from the Dementia Study of Western Norway. The participants had mild Alzheimer disease and Lewy body dementia. Apolipoprotein E ?4 gene variant allele status was classified as one or more ?4 versus any other. Mini-Mental State Examination (MMSE) was measured at baseline and for 5 consecutive years. Mann-Whitney U tests and linear mixed-effects models were used for statistical analysis. Results:There were no significant differences in serum concentrations of tryptophan and kynurenine according to the presence or absence of APOE?4. High serum concentrations of kynurenic acid, quinolinic acid, and picolinic acid, and a higher kynurenine-to-tryptophan ratio, were all associated with more cognitive decline in patients without APOE?4 compared to those with the APOE?4 allele (P-value of the interactions?

SUBMITTER: Ervik AO

PROVIDER: S-EPMC6859685 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein ε4 Allele Variant in Patients With Dementia.

Ervik Arne Olav AO Solvang Stein-Erik Hafstad SH Nordrehaug Jan Erik JE Ueland Per Magne PM Midttun Øivind Ø Hildre Audun A McCann Adrian A Nygård Ottar O Aarsland Dag D Giil Lasse Melvaer LM

International journal of tryptophan research : IJTR 20191115

<h4>Background</h4>The apolipoprotein E ε4 gene variant (APOEε4) confers considerable risk for dementia and affects neuroinflammation, brain metabolism, and synaptic function. The kynurenine pathway (KP) gives rise to neuroactive metabolites, which have inflammatory, redox, and excitotoxic effects in the brain.<h4>Aim</h4>To assess whether the presence of at least one APOEε4 allele modifies the association between kynurenines and the cognitive prognosis.<h4>Methods</h4>A total of 152 patients wi ...[more]

PMID: 31798303

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Project description:ObjectivesTo confirm associations of apolipoprotein E (ApoE) ε4 carrier status, sex, and time-dependent cognitive status with mortality risk and to investigate these joint effects of these associations in a cohort of community-dwelling U.S. adults.DesignProspective cohort study.SettingThe Baltimore Longitudinal Study of Aging (BLSA).ParticipantsOf 3,047 BLSA participants aged 17 to 98 at first visit (60.1% male), 1,704 with complete ApoE genotype data were included, of whom 1,461 aged 50 and older with one or more visits were eligible.MeasurementsTime to death from all, cardiovascular, and noncardiovascular causes.ResultsProbability of survival was lower for ApoE ε4 carriers, particularly those who were older. A Cox proportional hazards model for all-cause mortality yielded a hazard ratio (HR) for ApoE ε4 carrier versus noncarriers of 1.31 (95% confidence interval (CI) = 1.02-1.68). This association was also found for cardiovascular mortality. Time-dependent all-cause dementia (HR = 1.73, 95% CI = 1.33-2.26) and mild cognitive impairment (HR = 1.95, 95% CI = 1.42-2.67) increased all-cause mortality risk, associations that were also detected for noncardiovascular mortality. When individuals were free of cognitive impairment, a dose-response relationship with ε4 alleles was found for all-cause mortality (HR = 1.40, 95% CI = 0.94-2.07 for 1 ε4; HR = 2.61, 95% CI = 1.12-6.07 for 2 ε4). After onset of Alzheimer's disease (AD), carrying only one ε4 allele resulted in an approximately 77% greater all-cause mortality risk than in noncarriers. ApoE ε4 carrier status increased all-cause mortality risk in men and interacted with time-dependent AD to increase the risk of this outcome (relative excess risk due to interaction = 2.15, 95% CI = 1.22-3.07).ConclusionApoE ε4 carrier status was found to increase all-cause and cardiovascular mortality risks and interacted with sex and time-dependent AD status to affect all-cause mortality.

Dataset Information

The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein ?4 Allele Variant in Patients With Dementia.

Publications

The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein ε4 Allele Variant in Patients With Dementia.

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