Dataset Information

Sleep and APOE-ε4 have a synergistic effect on plasma biomarkers and longitudinal cognitive decline in older adults.

ABSTRACT:

Background

Sleep disorders are prevalent among patients with Alzheimer's disease (AD), and the APOE ε4 genotype is a key genetic risk factor for sporadic AD. However, the combined effect of the genotype and sleep disorders on cognitive decline remains uncertain.

Methods

A total of 972 participants were drawn from the SILCODE cohort, comprising 655 without the ε4 allele (APOE-) and 317 with ε4 allele (APOE+). Data were collected, including neuropsychological assessments, sleep measurements, plasma biomarkers, and PET imaging. A Sleep Composite Index (SCI) was created, categorizing participants into high risk (Sleep+) and low risk (Sleep-).

Results

Significant predictions of dementia risk associated with plasma p-tau181, neurofilament light chain (NfL), and SCI. Individuals with both Sleep+ and APOE+ had a higher risk of dementia compared to those with Sleep-. The Sleep+/APOE+ group had higher plasma NfL levels than the Sleep-/APOE- group. Similar trends emerged in plasma NfL levels among the Aβ PET-positive subgroup. Plasma NfL levels explained 23% of the relationship between SCI and cognitive impairment.

Conclusion

Our study highlights sleep disorder was associated with cognitive decline, with plasma NfL playing a partial mediating role. These findings explain how sleep disorders affect cognitive function and emphasize the importance of healthy sleep for older adults.

SUBMITTER: Yu X

PROVIDER: S-EPMC10850800 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Sleep and APOE-ε4 have a synergistic effect on plasma biomarkers and longitudinal cognitive decline in older adults.

Yu Xianfeng X Zhou Xia X He Zhengbo Z He Beiqi B Wan Ke K Wei Min M Guo Tengfei T Han Ying Y

CNS neuroscience & therapeutics 20240201 2

<h4>Background</h4>Sleep disorders are prevalent among patients with Alzheimer's disease (AD), and the APOE ε4 genotype is a key genetic risk factor for sporadic AD. However, the combined effect of the genotype and sleep disorders on cognitive decline remains uncertain.<h4>Methods</h4>A total of 972 participants were drawn from the SILCODE cohort, comprising 655 without the ε4 allele (APOE-) and 317 with ε4 allele (APOE+). Data were collected, including neuropsychological assessments, sleep meas ...[more]

PMID: 38421124

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Project description:ObjectiveTo exam the association of cognitive decline with APOE ε4 allele carriage and dietary protein intake and investigate whether there is a gene-diet (GxD) interaction of APOE ε4 allele carriage and dietary protein intake on cognitive decline in a nationwide cohort of older adults.MethodsA cohort study of participants from Chinese Longitudinal Healthy Longevity Survey was conducted from 2008 to 2014. A total of 3029 participants (mean age of 77.0 years, SD = 9.0; 49.3% were women) was enrolled. We genotyped APOE ε4 allele for each participant and calculated the diversity of dietary protein intake (DDPI) by summing up the frequency of intake of the 6 protein-rich foods (meats, fish, eggs, nuts, dairy products, and bean products). We assessed cognitive function using the Mini-Mental State Examination (MMSE). We used ordinal regression model to estimate the independent and joint effects of APOE ε4 carrier and dietary protein intake on cognitive decline, adjusting for potential confounders of age, sex, education, socio-economic status, lifestyles, BMI, and cardiometabolic conditions.ResultsThere was significant association between carrying APOE ε4 allele and faster cognitive decline (Odds ratio: 1.19, 95% CI = 1.00-1.42), independent of potential confounders. While the associations of DDPI and the intake of 6 protein-rich foods with cognitive decline did not reach any statistical significance. We observed significant interactions of APOE ε4 with DDPI and fish intake, at multiple correction-adjusted Ps < 0.05. In those who were APOE ε4 carriers rather than non-carriers, both high DDPI (OR = 0.54, 95% CI: 0.34-0.88) and daily fish intake (OR = 0.43, 95% CI: 0.22-0.78) were significantly associated with slower cognitive decline, respectively. We also found that frequent intake of fish benefits women more than men regarding the mitigating of cognitive decline among APOE ε4 allele carriers (P for interaction = 0.016).ConclusionsThe results of this study support the hypothesis that diversified protein food intake in addition to frequent fish intake may reduce the detrimental effect of APOE ε4 on cognitive health.

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.

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Dataset Information

Sleep and APOE-ε4 have a synergistic effect on plasma biomarkers and longitudinal cognitive decline in older adults.

Background

Methods

Results

Conclusion

Publications

Sleep and APOE-ε4 have a synergistic effect on plasma biomarkers and longitudinal cognitive decline in older adults.

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