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Interactive Effects of Apolipoprotein E ?4 and Triiodothyronine on Memory Performance in Patients With Subjective Cognitive Decline.

ABSTRACT: Background: The aim of the present study was to investigate the associations between thyroid hormones, cognitive performance, and apolipoprotein E (APOE) genotype in euthyroid patients with subjective cognitive decline (SCD). Methods: We recruited 197 euthyroid patients that fulfilled the criteria for SCD. All participants were classified into APOE ?4 carriers and non-carriers based on the presence of the APOE ?4 allele. Patients with SCD who had the APOE ?2/?4 genotype were excluded from the study. We then performed correlation and regression analyses to evaluate the associations between cognitive performance and thyroid hormones in APOE ?4 carriers and non-carriers. Results: We found no significant differences in cognitive function between APOE ?4 carriers and non-carriers. However, higher levels of triiodothyronine (T3) were associated with better verbal memory performance (immediate and delayed recall tasks) in APOE ?4 carriers, whereas a negative association was found in APOE ?4 non-carriers. Furthermore, there was a significant interactive effect of APOE ?4 status and T3 levels on verbal memory performance (immediate and delayed recall tasks). Conclusions: These findings suggest that in patients with SCD, T3 might have a protective effect on memory in those who are APOE ?4 carriers. The differential susceptibility hypothesis would thus support a gene-by-hormone crossover interaction between APOE ?4 allele and T3 in this study. Early identification and intervention of high-risk individuals for cognitive decline is important to establish new strategies for preventing dementia.

SUBMITTER: Lee JS

PROVIDER: S-EPMC7330104 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Interactive Effects of Apolipoprotein E ε4 and Triiodothyronine on Memory Performance in Patients With Subjective Cognitive Decline.

Lee Jin San JS Soh Yunsoo Y Kim Hyug-Gi HG Lee Kyung Mi KM Kwon Young Nam YN Yoon Sung Sang SS Park Key-Chung KC Rhee Hak Young HY

Frontiers in medicine 20200625

Background: The aim of the present study was to investigate the associations between thyroid hormones, cognitive performance, and apolipoprotein E (APOE) genotype in euthyroid patients with subjective cognitive decline (SCD). Methods: We recruited 197 euthyroid patients that fulfilled the criteria for SCD. All participants were classified into APOE ε4 carriers and non-carriers based on the presence of the APOE ε4 allele. Patients with SCD who had the APOE</i ...[more]

PMID: 32671080

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Project description:Cognitive complaints are common in elderly subjects and are a frequent reason for referral to memory clinics. If the complaints are not associated with objective cognitive impairment, the condition is labelled subjective cognitive decline (SCD). SCD is often considered as a stage antedating objective impairment, and an at-risk condition for subsequent dementia. Recent large-scale studies indicate that a significantly increased risk of clinical progression in subjects with SCD is associated with positivity for Alzheimer's disease (AD) biomarkers, a finding supporting the notion that SCD can be due to different mechanisms not associated with neurodegeneration, including functional cognitive disorders. In this paper we present a selective review of research on the relations among SCD, cognitive awareness, and metacognitive abilities. We propose that longitudinal studies of metacognitive efficiency in SCD may provide useful cues about the risk of progression to dementia and the possible presence of a functional cognitive disorder, with different implications for the management of this prevalent aging-related condition. HIGHLIGHTS: Subjective cognitive decline (SCD), a common cause of referral to memory clinics, can be due to multiple conditions. The predictive value of SCD for progression to Alzheimer's disease (AD) dementia is high in association with AD biomarker positivity. The awareness of cognitive decline is the mechanism responsible for the emergence of SCD and metacognition is the underlying neuropsychological function. The awareness of cognitive decline in clinical patients is usually assessed comparing an informant rating to the patient self-assessment, a method that can be affected by informant bias. While there is strong evidence that awareness starts to decline with the onset of objective cognitive impairment, progressively leading to the anosognosia of AD, the status of metacognitive efficiency in SCD needs to be further investigated. Quantitative, performance-based indexes of metacognitive efficiency may contribute both to the assessment of progression risk and to the management of subjects with functional cognitive disorders.

Project description:BackgroundSubjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ε4 allele is thought to be a genetic marker associated with risk of SCD. Neuropsychiatric symptoms may provide insight in detecting higher-risk elders for early Alzheimer's disease as well. Therefore, we aim to explore the characteristics of brain morphology in SCD and to determine whether it is influenced by APOE ε4 as well as neuropsychiatric symptoms in SCD.MethodsA total of 138 cognitively normal older individuals from the SILCODE cohort underwent a clinical interview, neuropsychological assessments, a blood test, and MRI. A two-sample t-test was used to examine the cortex volume and bilateral cortical surface area alterations between SCD (n = 65) and controls (n = 73). A general linear model analysis was used to test for both main and interaction effects of clinical phenotype (SCD vs. controls) and APOE on global and regional cortex volume and bilateral cortical surface area and thickness. A multiple linear regression analysis was conducted to determine the effects of the APOE genotype on the relationships between morphometric features and neuropsychiatric symptoms in SCD.ResultsCompared with controls, individuals with SCD showed decreased total cortical volumes and cortical surface area. SCD APOE ε4 carriers showed additive reduction in the right cortical surface area. The evaluation scores of anxiety symptoms were negatively associated with the right cortical surface area in SCD APOE 4 non-carriers.ConclusionsIndividuals with SCD had an altered cortical surface area, and APOE genotype and anxiety symptoms are modified factors on the cortical surface area decrease in SCD.Trial registrationClinicalTrials.gov (Identifier: NCT03370744 ). Registered 15 March 2017.

Project description:IntroductionSubjects exhibiting subjective cognitive decline (SCD) are at an increased risk for mild cognitive impairment and dementia. Given the delay between risk exposure and disease onset, SCD individuals are increasingly considered a good target population for cost-effective lifestyle-based Alzheimer's disease prevention trials.MethodsThe PENSA study is a randomized, double-blind, controlled clinical trial that aims to evaluate the efficacy of a personalized multimodal intervention in lifestyle (diet counseling, physical activity, cognitive training, and social engagement) combined with the use of epigallocatechin gallate (EGCG) over 12 months, in slowing down cognitive decline and improving brain connectivity. The study population includes 200 individuals meeting SCD criteria and carrying the apolipoprotein E ε4 allele, who will be randomized into four treatment arms (multimodal intervention + EGCG/placebo, or lifestyle recommendations + EGCG/placebo). The primary efficacy outcome is change in the composite score for cognitive performance measured with the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC-like) adding to the original version the Interference score from the Stroop Color and Word Test and the Five Digit Test. Secondary efficacy outcomes are (1) change in functional magnetic resonance imaging (fMRI) and structural neuronal connectivity (structural MRI) and (2) the safety assessment of the EGCG compound. This study is framed within the WW-FINGERS consortium.DiscussionThe use of new technologies (i.e., mobile ecological momentary assessments [EMAs], activity tracker) in the PENSA study allows the collection of continuous data on lifestyle behaviors (diet and physical activity) and mood, enabling a personalized design as well as an intensive follow-up of participants. These data will be used to give feedback to participants about their own performance along the intervention, promoting their involvement and adherence. The results of the study may aid researchers on the design of future clinical trials involving preventive lifestyle multicomponent interventions.

Dataset Information

Interactive Effects of Apolipoprotein E ?4 and Triiodothyronine on Memory Performance in Patients With Subjective Cognitive Decline.

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Interactive Effects of Apolipoprotein E ε4 and Triiodothyronine on Memory Performance in Patients With Subjective Cognitive Decline.

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