| 1. |
- Dong, Yi, et al.
(författare)
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Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer's Disease Clinical Spectrum: A Population-Based Study
- 2023
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Ingår i: JOURNAL OF ALZHEIMERS DISEASE. - 1387-2877 .- 1875-8908. ; 96:2, s. 845-858
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Tidskriftsartikel (refereegranskat)abstract
- Background: Plasma biomarkers have emerged as a promising approach for characterizing pathophysiology in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Objective: We aimed to characterize plasma biomarkers for AD and neurodegeneration across the AD clinical continuum, and to assess their ability to differentiate between AD, MCI, and normal cognition. Methods: This population-based study engaged 1,446 rural-dwelling older adults (age >= 60 years, 61.0% women) derived from MIND-China; of these, 402 were defined with MCI and 142 with AD. Plasma amyloid-beta (A beta), total tau (t-tau), and neurofilament light chain (NfL) concentrations were analyzed using the Simoa platform. Data were analyzed using linear and logistic regression models, and receiver operating characteristic (ROC) analysis. Results: Across the AD clinical spectrum, plasma A beta(40) and NfL increased, whereas A beta(42)/A beta(40) ratio decreased. Plasma t-tau was higher in people withADdementia than those with MCI or normal cognition. Plasma NfL outperformed other biomarkers in differentiating AD from normal cognition (area under the ROC curve [AUC] = 0.75), but all plasma biomarkers performed poorly to distinguish MCI from normal cognition (AUC <0.60). Plasma NfL in combination with age, sex, education, and APOE genotype yielded the AUC of 0.87 for differentiating between AD and normal cognition, 0.79 between AD and MCI, and 0.64 between MCI and normal cognition. Conclusions: In this Chinese population, AD plasma biomarkers vary by age, sex, and APOE genotype. Plasma A beta, t-tau, and NfL differ across the AD clinical spectrum, and plasma NfL appears to be superior to plasma A beta and t-tau for defining the clinical spectrum.
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| 2. |
- Liang, Xiaoyan, et al.
(författare)
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Association and interaction of TOMM40 and PVRL2 with plasma amyloid-β and Alzheimer's disease among Chinese older adults : a population-based study
- 2022
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 113, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies have identified Alzheimer's disease (AD)-associated SNPs in TOMM40 and PVRL2 genes, but the underlying mechanisms remain unknown. We examined their associations and interactions with AD risk and plasma biomarkers among Chinese older adults. This population-based study included 4876 participants. TOMM40(rs2075650) and PVRL2(rs6859) polymorphisms were detected using multiple-polymerase chain reaction amplification. Plasma Aβ40, Aβ42, and t-tau concentrations were measured using SIMOA in a subsample (n = 1257). AD was diagnosed following the international criteria. Data were analyzed using multiple logistic and general linear models. AD was diagnosed in 182 participants. The multiadjusted odds ratio of AD was 6.24 (95% CI 1.73–22.48) for TOMM40GG, 1.47 (0.89–2.42) for PVRL2AA, and 12.87 (3.97–41.73) for having both risk alleles (Pinteraction = 0.0003). Among APOEε3/ε3 carriers, the multiadjusted odds ratio of AD associated with TOMM40AG was 2.90(1.15–7.31). In biomarker subsample, TOMM40GG was significantly associated with lower plasma Aβ42 and the Aβ42-to-Aβ40 ratio (p < 0.05). TOMM40 genotype is differentially associated with AD risk depending on APOE genotype. TOMM40 and PVRL2 genes could interact to substantially increase AD risk, possibly through influencing Aβ metabolism.
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| 3. |
- Tian, Na, et al.
(författare)
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Triglyceride-glucose index, Alzheimer's disease plasma biomarkers, and dementia in older adults : The MIND-China study
- 2023
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - 2352-8729. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Population-based studies have rarely explored the associations of the triglyceride–glucose (TyG) index, a surrogate marker of insulin resistance, with dementia and plasma biomarkers for amyloid beta (Aβ) and neurodegeneration.Methods: This population-based study included 5199 participants (age ≥ 65 years); of these, plasma Aβ, total tau, and neurofilament light chain (NfL) were measured in 1287 persons. Dementia and subtypes were diagnosed following the international criteria. TyG index was calculated as ln(fasting triglyceride(mg/dL) × fasting glucose[mg/dL]/2). Data were analyzed using logistic and general linear regression models.Results: Dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were diagnosed in 301, 195, and 95 individuals, respectively. A high TyG index was significantly associated with increased likelihoods of dementia and AD; the significant association with dementia remained among participants without cardiovascular disease or diabetes. In the biomarker subsample, a high TyG index was correlated with elevated plasma Aβ, but not with total tau or NfL.Discussion: High TyG index is associated with dementia, possibly via Aβ pathology.
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| 4. |
- Cheng, Yingzhe, et al.
(författare)
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Genetic Effects of NDUFAF6 rs6982393 and APOE on Alzheimer’s Disease in Chinese Rural Elderly : A Cross-Sectional Population-Based Study
- 2022
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Ingår i: Clinical Interventions in Aging. - 1176-9092 .- 1178-1998. ; 17, s. 185-194
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the associations of genotypes of NDUFAF6 rs6982393 and APOE and their combined genotypes with the risk of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) in Chinese rural elderly.Methods: This cross-sectional population-based study included 5096 older adults (age ≥ 60 years, 57.1% female). Genotypes of NDUFAF6 rs6982393 and APOE were detected using the multiple-polymerase chain reaction amplification. We diagnosed AD following the criteria of Diagnostic and Statistical Manual of Mental Disorders, the fourth edition and diagnosed MCI following the Petersen’s criteria MCI. Data were analyzed using the logistic regression model.Results: The overall prevalence of AD and MCI was 3.57% (95% confidence interval [CI]: 0.040, 0.053) and 22.65% (95% CI: 0.223, 0.247), separately. The TT versus CC/CT genotype of NDUFAF6 rs6982393 was related to a higher risk of AD with the multi-adjusted odds ratio (95% CI) being 1.61 (1.02, 2.54) in the total sample, 3.36 (1.48, 7.60) in those aged 60– 69, and 1.24 (0.71, 2.17) in those aged 70 years and above. The interaction between genotype of NDUFAF6 rs6982393 with age groups (60– 69 versus ≥ 70 years) was significant on the risk of AD. The presence of APOE ϵ4 was not significantly associated with the risk of AD. Carrying both NDUFAF6 TT and APOE ϵ4 was related to a higher risk of AD with the multi-adjusted odds ratio (95% CI) being 2.69 (1.10, 2.56). In addition, there was no significant association between the above genotypes and MCI.Conclusion: In Chinese rural elderly, the TT versus CT/CC genotype of NDUFAF6 rs6982393 was associated with an increased likelihood of AD; such an association only existed among young-old adults. Carrying both NDUFAF6 rs6982393-TT and APOE ϵ4 was related to a higher risk of AD. This finding highlights the importance of considering age and combined genotype in studying the genetic profiles of AD.
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| 5. |
- Han, Xiaolei, et al.
(författare)
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Accelerometer-measured sedentary behavior patterns, brain structure, and cognitive function in dementia-free older adults : a population-based study
- 2023
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 96:2, s. 657-668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood.Objective: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms.Methods: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018-2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models.Results: In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (ptrend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores.Conclusion: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association.
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| 6. |
- Mao, Ming, et al.
(författare)
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Ventricular Electrocardiographic Signatures Associated with Dementia and Plasma Alzheimer's Disease Biomarkers in Older Adults : A Population-Based Study
- 2023
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 94:4, s. 1515-1526
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence has emerged that altered ventricular electrocardiogram profiles are associated with dementia, but the neuropathological mechanisms underlying their associations are poorly understood. Objective: To investigate the interrelationships of ventricular electrocardiogram profiles with dementia and plasma Alzheimer's disease (AD) biomarkers among older adults. Methods: This population-based cross-sectional study included 5,153 participants (age >= 65 years; 57.3% women) living in rural communities in China; of these, 1,281 had data on plasma amyloid-beta (A beta)(40), A beta(42), total-tau, and neurofilament light chain (NfL) protein. The QT, QTc, JT, JTc, QRS intervals, and QRS axis were derived from the 10-second electrocardiogram recording. The DSM-IV criteria were followed for clinical diagnosis of dementia, the NIA-AA criteria for AD, and the NINDS-AIREN criteria for vascular dementia (VaD). Data were analyzed using general linear models, multinomial logistic models, and restricted cubic splines. Results: Of the 5,153 participants, 299 (5.8%) were diagnosed with dementia, including 194 with AD and 94 with VaD. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with all-cause dementia, AD, and VaD (p < 0.05). Left QRS axis deviation was significantly associated with all-cause dementia and VaD (p < 0.01). In the subsample of plasma biomarkers (n = 1,281), prolonged QT, JT, and JTc intervals were significantly associated with a lower A beta(42)/A beta(40) ratio and higher plasma NfL concentrations (p < 0.05). Conclusion: Alterations in ventricular repolarization and depolarization are independently associated with all-cause dementia, AD, VaD, and AD plasma biomarkers in older adults (age >= 65 years). Ventricular electrocardiogram parameters may be valuable clinical markers for dementia and the underlying AD pathologies and neurodegeneration.
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| 7. |
- Ren, Yifei, et al.
(författare)
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Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults : A population-based study
- 2024
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Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1550-1561
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults.METHODS: This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models.RESULTS: The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05).DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults.
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| 8. |
- Tian, Na, et al.
(författare)
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Association of Triglyceride-Glucose Index With Cognitive Function and Brain Atrophy : A Population-Based Study
- 2024
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Ingår i: The American journal of geriatric psychiatry. - 1064-7481 .- 1545-7214. ; 32:2, s. 151-162
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the associations of triglyceride-glucose (TyG) index, a reliable surrogate marker for insulin resistance, with the function of various cognitive domains and brain structures among older adults.Design: A population-based cross-sectional study.Setting: Older adults living in the rural communities in China.Participants: About 4,541 rural-dwelling dementia-free participants (age ≥65 years; 56.37% women) undertook examinations in March–September 2018 for MIND-China.Measurements: TyG index was calculated as ln[fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. A neuropsychological test battery was used to assess memory, attention, verbal fluency, and executive function. Volumetric brain measures were assessed on magnetic resonance imaging (MRI) in a subsample (n = 1,019). Data were analyzed with restricted cubic spline and multivariable general linear models.Results: An inverted J-shaped association was observed between TyG index and z-scores of multiple cognitive domains, such that among individuals with TyG index ≥8.57 (median), a higher TyG index was significantly associated with lower z-scores of memory, attention, verbal fluency, executive function, and global cognition (all p < 0.05); among people with TyG index <8.57, a higher TyG index was significantly associated with a higher executive function z-score (p < 0.05), but not with any of the other examined cognitive domains. In the MRI subsample, a higher TyG index was significantly associated with lower volumes of total brain tissue, gray matter, and white matter as well as greater cerebrospinal fluid volume (p < 0.05), but not with white matter hyperintensity volume.Conclusions: Insulin resistance, as indicated by a high TyG index, was associated with poor function in multiple cognitive domains and global brain atrophy.
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| 9. |
- Wang, Chaoqun, et al.
(författare)
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Associations of Cardiac Ventricular Repolarization with Serum Adhesion Molecules and Cognitive Function in Older Adults : The MIND-China Study
- 2023
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 92:1, s. 273-283
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging evidence has linked electrocardiographic parameters with serum adhesion molecules and cognition; however, their interrelationship has not been explored.Objective: We sought to investigate the associations of ventricular depolarization and repolarization intervals with serum adhesion molecules and cognitive function among rural-dwelling older adults.Methods: This population-based study engaged 4,886 dementia-free participants (age ≥60 years, 56.2% women) in the baseline examination (March-September 2018) of MIND-China. Of these, serum intercellular and vascular adhesion molecules (ICAM-1 and VCAM-1) were measured in 1591 persons. We used a neuropsychological test battery to assess cognitive function. Resting heart rate, QT, JT intervals, and QRS duration were assessed with electrocardiogram. Data were analyzed using general linear models adjusting for multiple confounders.Results: Longer JT interval was significantly associated with lower z-scores of global cognition (multivariable-adjusted β= –0.035; 95% confidence interval = –0.055, –0.015), verbal fluency (–0.035; –0.063, –0.007), attention (–0.037; –0.065, –0.010), and executive function (–0.044; –0.072, –0.015), but not with memory function (–0.023; –0.054, 0.009). There were similar association patterns of QT interval with cognitive functions. In the serum biomarker subsample, longer JT and QT intervals remained significantly associated with poorer executive function and higher serum adhesion molecules. We detected statistical interactions of JT interval with adhesion molecules (pinteraction <0.05), such that longer JT interval was significantly associated with a lower executive function z-score only among individuals with higher serum ICAM-1 and VCAM-1.Conclusion: Longer ventricular depolarization and repolarization intervals are associated with worse cognitive function in older adults and vascular endothelial dysfunction may play a part in the associations.
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| 10. |
- Wang, Yongxiang, et al.
(författare)
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Health status and risk profiles for brain aging of rural‐dwelling older adults : Data from the interdisciplinary baseline assessments in MIND‐China
- 2022
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Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Multidomain intervention approaches have emerged as a potential strategy to reduce dementia risk. We sought to describe the baseline assessment approaches, health conditions, and risk profiles for brain aging of participants in the randomized controlled Multimodal INterventions to delay Dementia and disability in rural China (MIND-China).Methods: MIND-China engaged residents who were >= 60 years of age and living in rural communities in the western Shandong province. In March to September 2018, all participants underwent the core module assessments via face-to-face interviews, clinical examinations, neuropsychological testings, and laboratory tests. Specific modules of examination were performed for sub-samples, including brain magnetic resonance imaging scans, genetic and blood biochemical markers, actigraphy testing, cardiopulmonary coupling analysis for sleep quality and disturbances, audiometric testing, and optical coherence tomography examination. We performed descriptive analysis.Results: In total, 5765 participants (74.9% of all eligible residents) undertook the baseline assessments. The mean age was 70.9 years (standard deviation, 5.9), 57.2% were women, 40.6% were illiterate, and 88.3% were farmers. The overall prevalence of common chronic diseases was 67.2% for hypertension, 23.4% for dyslipidemia, 23.5% for heart disease, 14.4% for diabetes mellitus, and 5.4% for dementia. The prevalence rates of hypertension, diabetes mellitus, dyslipidemia, obesity, heart disease, depressive symptoms, and dementia were higher in women than in men (P < .05). Overall, 87.1% of the participants had at least two of the 15 chronic diseases (89.3% in women vs 84.2% in men, P < .001). Participants examined for the specific modules were younger, more likely to be women, and more educated than those not examined.Discussion: Comprehensive baseline assessments of participants in MIND-China provide extremely valuable data sources for interdisciplinary research into the complex relationships of aging, health, brain aging, and functional consequences among older adults living in the rural communities.Highlights:MIND-China is a multimodal intervention study among rural residents >= 60 years of age.At baseline, 5765 participants undertook the interdisciplinary assessments.The baseline assessments consisted of core module and specific modules.Specific modules included brain magnetic resonance imaging (MRI), blood biomarkers, ActiGraph, cardiopulmonary coupling (CPC), pure-tone audiometry (PTA), and optical coherence tomography (OCT).
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