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1.
  • Cheng, Yingzhe, et al. (författare)
  • Genetic Effects of NDUFAF6 rs6982393 and APOE on Alzheimer’s Disease in Chinese Rural Elderly : A Cross-Sectional Population-Based Study
  • 2022
  • Ingår i: Clinical Interventions in Aging. - 1176-9092 .- 1178-1998. ; 17, s. 185-194
  • 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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2.
  • Cong, Lin, et al. (författare)
  • Mild cognitive impairment among rural-dwelling older adults in China : A community-based study
  • 2023
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:1, s. 56-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological studies of mild cognitive impairment (MCI) and subtypes of MCI have rarely focused on rural residents in China.Methods: This population-based study included 5068 participants (age >= 60 years) who were living in rural communities. We defined MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) following the Petersen's criteria that integrated neuropsychological assessments with in-person clinical evaluations.Results: The overall prevalence of MCI, aMCI, and naMCI was 26.48%, 22.30%, and 4.18%, respectively. The prevalence of MCI increased with age. The adjusted odds ratio (OR) of MCI was 0.71 (95% confidence interval [CI] 0.61 to 0.82) for primary school (vs. illiteracy), 0.30 (0.24 to 0.39) for middle school or above, 1.35 (1.09 to 1.67) for being farmers, 0.65 (0.54 to 0.78) for alcohol consumption, 1.43 (1.20 to 1.70) for stroke history, and 1.14 (0.95 to 1.36) for any apolipoprotein E (APOE) epsilon 4 allele (vs epsilon 3/epsilon 3).Conclusions: MCI affects over one-fourth of rural older adults in China. Overall MCI was associated with demographic factors, non-alcohol consumption, and stroke, but not with APOE genotype and cardiometabolic factors.
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3.
  • Cong, Lin, et al. (författare)
  • Use of Cardiovascular Drugs for Primary and Secondary Prevention of Cardiovascular Disease Among Rural-Dwelling Older Chinese Adults
  • 2020
  • Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiovascular risk factors and related disorders are common among older adults, and use of various classes of cardiovascular (CV) drugs could reduce the risk of cardiovascular disease (CVD). However, data are sparse with regard to the use of CV drugs among rural-dwelling older adults in China. Therefore, this population-based study aimed to describe use of CV drugs among older adults living in the rural communities in China, while taking into account the use of CV drugs for primary and secondary prevention of CVDs. This study included 5,246 participants (age >= 65 years; 57.17% women; 40.68% illiteracy) in the baseline examination of the MIND-China study. In March-September 2018, data on health-related factors, CVDs (ischemic heart disease, atrial fibrillation, heart failure, and stroke), and CV drug use were collected via face-to-face survey, clinical examination, and laboratory tests. We classified CV drugs according to the Anatomical Therapeutic Chemical classification system for western medications and specific cardiovascular effects for the products of traditional Chinese medicine (TCM). We conducted descriptive analysis. The overall prevalence of major cardiovascular risk factors ranged from 14.30% in diabetes and 23.81% in dyslipidemia to 66.70% in hypertension, and CVDs affected 35.07% of all participants (36.28% in women vs. 33.47% in men, p = 0.035). In the total sample, calcium channel blockers (C08) were most commonly used (10.39%), followed by TCM products (7.64%), hypoglycemic agents (A10, 4.73%), renin-angiotensin system (RAS)-acting agents (C09, 4.61%), and lipid-lowering agents (C10, 4.17%). The proportions of CV drugs for primary prevention (i.e., use of CV drugs among people without CVD) were 3.14% for antithrombotic agents (mainly aspirin), 1.38% for lipid-lowering agents, and 3.11% for RAS-acting agents; the corresponding figures for secondary prevention (i.e., use of CV drugs among people with CVD) were 13.97%, 9.35%, and 7.39%. In conclusion, despite highly prevalent cardiovascular risk factors and CVDs, a fairly low proportion of the rural-dwelling older adults take CV medications for primary and secondary prevention. Notably, TCM products are among the most commonly used CV drugs. These results call for additional efforts to promote implementation of the evidence-based recommendations for prevention of CVDs in the primary care settings.
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4.
  • Dong, Yi, et al. (författare)
  • Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults
  • 2023
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:2, s. 589-601
  • Tidskriftsartikel (refereegranskat)abstract
    • Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214 dementia-free participants (age ≥65 years). Olfaction was assessed using the 16-item Sniffin’ Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aβ)40, Aβ42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)-signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non-amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults.
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5.
  • Dong, Yi, et al. (författare)
  • Dementia screening in rural-dwelling Chinese older adults : The utility of a smell test and the self-rated AD8
  • 2022
  • Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 70:4, s. 1106-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Olfactory impairment is associated with dementia in clinical settings. We examined the relationship of olfactory identification function with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) and assessed the discriminative ability of the Sniffin' Sticks Identification Test (SSIT), the self-rated Ascertain Dementia 8-item Questionnaire (AD8), and their combination for dementia detection among rural-dwelling older adults in China.Methods: This population-based cross-sectional study included 4481 participants (age ≥ 65 years; 56.8% women; 38.1% illiteracy) living in rural communities. The 16-item SSIT was performed to assess olfactory identification function. The self-rated AD8 was administered to participants for cognitive status. We diagnosed dementia, AD, and VaD following the international criteria. Data were analyzed with logistic regression models and receiver operating characteristic curve.Results: Of the 4481 participants, dementia was diagnosed in 139 persons (3.1%), including 92 with AD and 42 with VaD. The SSIT score (range, 0–16) was associated with multiadjusted odds ratios of 0.83 (95% CI: 0.79–0.88) for dementia, 0.84 (0.79–0.90) for AD, and 0.79 (0.71–0.87) for VaD. The area under the curve for the discrimination between participants with and without dementia was 0.73 (95% CI: 0.69–0.77) for SSIT score ≤ 8 alone, 0.86 (0.82–0.89) for self-rated AD8 score ≥ 3 alone, and 0.89 (0.86–0.92) for their combination using a logistic model.Conclusions: Olfactory impairment is a clinical marker for all-cause dementia, AD, and VaD. The smell identification test, in combination with the brief self-rated cognitive screening tool, is accurate for screening dementia among rural-dwelling Chinese older adults with no or limited education.
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6.
  • Dong, Yi, et al. (författare)
  • Olfactory Impairment Among Rural-Dwelling Chinese Older Adults : Prevalence and Associations With Demographic, Lifestyle, and Clinical Factors
  • 2021
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Olfactory impairment (OI) refers to decreased (hyposmia) or absent (anosmia) ability to smell. We sought to estimate the prevalence and correlates of OI among rural-dwelling Chinese older adults.Methods: This population-based cross-sectional analysis included 4,514 participants (age >= 65 years; 56.7% women) from the Multidomain Interventions to Delay Dementia and Disability in Rural China (MIND-China). The 16-item Sniffin' Sticks identification test (SSIT) was used to assess olfactory function. Olfactory impairment was defined as the SSIT score <= 10, hyposmia as SSIT score of 8-10, and anosmia as SSIT score <8. Multivariable logistic regression models were used to examine factors associated with OI. Results: The overall prevalence was 67.7% for OI, 35.3% for hyposmia, and 32.5% for anosmia. The prevalence increased with age for OI and anosmia, but not for hyposmia. The multivariable-adjusted odds ratio (OR) of OI was 2.10 (95% CI 1.69-2.61) for illiteracy and 1.41 (1.18-1.70) for elementary school (vs. middle school or above), 1.30 (1.01-1.67) for current smoking (vs. never smoking), 0.86 (0.74-0.99) for overweight and 0.73 (0.61-0.87) for obesity (vs. normal weight), 4.21 (2.23-7.94) for dementia, 1.68 (1.23-2.30) for head injury, and 1.44 (1.14-1.83) for sinonasal disease. Illiteracy in combination with either male sex or diabetes was significantly associated with an over two-fold increased OR of OI (p for interactions <0.05).Conclusion: Olfactory impairment is highly prevalent that affects over two-thirds of rural-dwelling older adults in China. OI is correlated with illiteracy, current smoking, dementia, head injury, and sinonasal disease, but negatively associated with overweight or obesity. Olfactory impairment as a potential clinical marker of neurodegenerative disorders among older adults deserves further investigation.
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7.
  • Dong, Yi, et al. (författare)
  • Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer's Disease Clinical Spectrum: A Population-Based Study
  • 2023
  • Ingår i: JOURNAL OF ALZHEIMERS DISEASE. - 1387-2877 .- 1875-8908. ; 96:2, s. 845-858
  • 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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8.
  • Fa, Wenxin, et al. (författare)
  • Associations of Blood Absolute Neutrophil Count and Cytokines With Cognitive Function in Dementia-Free Participants : A Population-Based Cohort Study
  • 2023
  • Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1079-5006 .- 1758-535X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The relationships of neutrophils and cytokines with cognitive dysfunction are poorly defined. We aimed to investigate the association of peripheral blood absolute neutrophil count (ANC) with cognitive function in older adults and to further explore the mediating role of serum cytokines in this association.Methods: This population-based cohort study included 1 666 dementia-free participants (age ≥60 years) derived from baseline examinations (March–September 2018) of the Multimodal Intervention to Delay Dementia and Disability in Rural China (MIND-China); of these, 1 087 participants completed follow-up examinations in October–December 2019. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, and executive function at the baseline and follow-up examinations. We used Mindray BC-6800 automated hematology analyzer to measure ANC and Meso Scale Discovery to measure serum interleukin-6 (IL-6) and eotaxin-3.Results: The linear regression analysis of cross-sectional data at baseline (n = 1 666) suggested that increased ANC was significantly associated with a lower episodic memory z score (β coefficient: −0.149, 95% CI: −0.274 to −0.023) and lower long-delayed free recall z score (−0.216, −0.361 to −0.070). Serum IL-6 and eotaxin-3 could mediate 16.16% to 20.21% and 7.55% to 9.35%, respectively, of these associations. The analysis of longitudinal data (n = 1 087) showed a J-shaped relationship of ANC with decline in episodic memory z score (p for nonlinear = .049), and a U-shaped relationship between ANC and decline in long-delayed free recall z score (p for nonlinear = .043).Conclusions: Increased neutrophils are associated with poor cognitive performance and accelerated decline in episodic memory, and the cross-sectional association is partly mediated by serum cytokines.
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9.
  • Fan, Dong, et al. (författare)
  • Cardiovascular health profiles, systemic inflammation, and physical function in older adults : A population-based study
  • 2023
  • Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 109
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined the association of modifiable cardiovascular health (CVH) metrics with physical function among rural older adults in China and the potential role of inflammatory mechanisms in the association. This study included 3733 stroke-and dementia-free participants (age >= 65 years; 56.9% women) in the baseline survey of a multimodal intervention study in rural China. From March-September 2018, data were collected via face-to-face interviews, clinical assessments, and laboratory tests. The Short Performance Physical Battery (SPPB) test was performed to assess physical function. We defined six modifiable CVH metrics according to the modified American Heart Association's recommendations. Serum interleukin (IL)-6 was measured in a subsample (n = 1156). Data were analyzed with multiple general linear and logistic regression models and structural equation modeling. Poor physical function (SPPB score <= 9) was defined in 1443 participants. Ideal CVH (vs. poor CVH) was associated with multivariable-adjusted odds ratio of 0.60 (95%CI 0.48-0.75) for poor physical function. Ideal CVH was significantly associated with higher scores on balance, chair stand, and walking speed tests (all p < 0.05). Moreover, ideal CVH profile was associated with lower serum IL-6 (multivariable-adjusted beta=-0.04; 95% CI-0.06,-0.01). Mediation analysis revealed that serum IL-6 accounted for 14% of the association of CVH with total SPPB score and 10% of the association with walking speed score (p < 0.05). This study suggests that an ideal CVH profile is associated with better physical function among stroke-and dementia-free older adults, partly via inflammatory mechanisms. The preventive implications of these findings warrant further investigation in cohort studies.
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10.
  • Han, Xiaolei, et al. (författare)
  • Accelerometer-assessed sedentary behaviour among Chinese rural older adults : Patterns and associations with physical function
  • 2022
  • Ingår i: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 40:17, s. 1940-1949
  • Tidskriftsartikel (refereegranskat)abstract
    • Sedentary behaviour is associated with a range of adverse health conditions. Population-based studies have rarely examined the distribution and associated factors of accelerometer-measured sedentary behaviour patterns in rural-dwelling older adults. This population-based study included 2096 rural-dwelling older adults (age ≥60 years; 59.0% women) derived from baseline participants of the MIND-China Study. Total sedentary time and patterns (e.g., uninterrupted bouts and breaks) were derived from the hip-worn accelerometers for 7 days. Physical function was assessed using the Short Physical Performance Battery test. Data were analysed using general linear models. Overall, participants spent 58.8% of daily waking time in sedentary behaviour, with nearly half of sedentary time being accumulated through sedentary bouts of 30+ minutes. Men spent more total and accumulated sedentary time than women in each sedentary bout duration, while women had more daily 1+ minute sedentary bouts than men (all P < 0.001). Controlling for moderate-to-vigorous physical activity and other confounders, more prolonged sedentary time and fewer breaks were significantly associated with poor physical function, balance, lower limb strength, and walking speed (all P < 0.001). In older adults living in rural communities, prolonged sedentary behaviour and less frequent breaks are associated with poor physical function.
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11.
  • Han, Xiaolei, et al. (författare)
  • Accelerometer-measured sedentary behavior patterns, brain structure, and cognitive function in dementia-free older adults : a population-based study
  • 2023
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 96:2, s. 657-668
  • 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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12.
  • Han, Xiaolei, et al. (författare)
  • Association of Cardiovascular Health Metrics with Dementia in Rural Chinese Older Adults : A Population-Based Study
  • 2022
  • Ingår i: Clinical Interventions in Aging. - 1176-9092 .- 1178-1998. ; 17, s. 947-956
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: We explore the associations of individual and composite cardiovascular health metrics with all-cause dementia, Alzheimer’s disease, and vascular dementia among rural-dwelling older adults and the potential age variations in their associations.Patients and Methods: This community-based cross-sectional study included 4980 older adults (age ≥ 65 years; 57.23% women) from the baseline examination of MIND-China. In March–September 2018, data were collected via face-to-face interviews, clinical examinations, and laboratory test. We defined six cardiovascular health metrics according to the modified American Heart Association’s recommendations. We diagnosed dementia and its subtypes following the international criteria. Data were analyzed using logistic regression models.Results: Of all the participants, 250 were diagnosed with dementia, including 165 with Alzheimer’s disease and 75 with vascular dementia. Ideal composite global cardiovascular health metrics (vs poor composite metrics) were associated with a multi-adjusted odds ratio (95% confidence interval) of 0.62 (0.42– 0.93) for dementia, 0.88 (0.52– 1.48) for Alzheimer’s disease, and 0.31 (0.16– 0.60) for vascular dementia. Moreover, ideal biological cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.52 (0.28– 0.95) for dementia and 0.21 (0.06– 0.77) for vascular dementia in young–old adults (65– 74 years), whereas ideal behavioral cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.48 (0.26– 0.89) for dementia and 0.16 (0.06– 0.43) for vascular dementia in old–old adults (≥ 75 years).Conclusion: Our results suggest that ideal cardiovascular health metrics are cross-sectionally associated with a low likelihood of dementia and vascular dementia among rural-dwelling older Chinese adults. The associations vary with age, components of cardiovascular health metrics, and dementia subtypes.
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13.
  • Han, Xiaolei, et al. (författare)
  • KIBRA regulates amyloid β metabolism by controlling extracellular vesicles secretion
  • 2022
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 78
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Previous research has revealed that KIBRA controls secretion of extracellular vesicles (EVs) by inhibiting the proteasomal degradation of Rab27a and EVs play an important role in amyloid β (Aβ) metabolism and transmission during Alzheimer's disease (AD) pathogenesis. Here, we further test the hypothesis that KIBRA regulates Aβ metabolism via the endosomal-lysosomal system.Methods We generated KIBRA knockout mice on a 5XFAD background and KIBRA knockdown cells in murine HT22 cells with stably overexpressing APP. Various forms of Aβ and quantification of EVs were analyzed by biochemical methods and nanoparticle tracking analysis, respectively. Multivesicular bodies (MVBs) were visualized by electron microscopy and confocal fluorescent microscopy. In a population-based cohort (n = 1419), KIBRA genotypes and plasma Aβ levels were analyzed using multiple-PCR amplification and Simoa, respectively.Findings Multiple forms of Aβ were dramatically attenuated in KIBRA knockout mouse brain, including monomers, oligomers, and extracellular deposition, but KIBRA knockout had no effect on intraneuronal APP C-terminal fragment β (APP-CTFβ)/Aβ levels. KIBRA depletion also decreased APP-CTFβ/Aβ-associated EVs secretion and subsequently enhanced MVBs number. Furthermore, we found that excessive accumulation of MVBs harboring APP-CTFβ/Aβ promoted the MVBs-lysosome fusion for degradation and inhibition of lysosomal function rescued secretion of APP-CTFβ/Aβ-associated EVs. More importantly, whole exon sequencing of KIBRA in a large population-based cohort identified the association of KIBRA rs28421695 polymorphism with plasma Aβ levels.Interpretation These results demonstrate that KIBRA regulates Aβ metabolism via controlling the secretion of APP-CTFβ/Aβ-associated EVs.
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14.
  • Han, Xiaolei, et al. (författare)
  • Sex disparities in cardiovascular health metrics among rural-dwelling older adults in China : a population-based study
  • 2021
  • Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cardiovascular health (CVH) metrics among Chinese older adults are poorly understood. We investigated sex disparities in CVH metrics and their management among rural-dwelling older adults in China.Methods: This community-based study included 5026 participants (age >= 65years; 57.2% women) in the baseline survey of a multimodal intervention study in rural China. In March-September 2018, data were collected through face-to-face interviews, clinical examinations, and laboratory tests. We defined six CVH metrics (three behavioral factors-smoking, body mass index, and physical activity; three biological factors-blood pressure, total cholesterol, and blood glucose) following the modified American Heart Association's recommendations. We performed descriptive analysis separately for men and women.Results: Of all participants, only 0.8% achieved ideal levels in all six CVH metrics. Men were more likely than women to have ideal levels in all CVH metrics but smoking. Women had higher prevalence of ideal global (9.7% vs. 7.8%) and behavioral (18.3% vs. 9.5%) CVH metrics (p<0.001), whereas men had higher prevalence of ideal biological CVH metrics (5.4% vs. 3.5%, p<0.001). The prevalence of ideal global and behavioral CVH metrics increased with age in both women and men (p for trend<0.001). Women were more likely to be aware of their hypertension and diabetes, and to receive antihypertensive treatment, while men were more likely to achieve the goal of high cholesterol treatment (p<0.05).Conclusions: The CVH metrics among older adults living in the rural communities in China are characterized by an extremely low proportion of optimal global CVH metrics and distinct sex differences, alongside poor management of major biological risk factors.
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15.
  • Jiang, Ziying, et al. (författare)
  • Red Cell Distribution Width and Dementia Among Rural-Dwelling Older Adults : The MIND-China Study
  • 2021
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 83:3, s. 1187-1198
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence has emerged that anemia is associated with dementia, but data on the relationships of red blood cell distribution width (RDW) with dementia and cognitive function in older adults are sparse.Objective: We sought to investigate the associations of RDW with dementia and global cognitive performance among rural-dwelling Chinese older adults and further to examine their associations by anemia status.Methods: This population-based cross-sectional study included 5,115 participants (age≥65 years, 57.0%women) in the baseline examination (March-September 2018) of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-CHINA). We collected data through face-to-face interviews, clinical examinations, and laboratory tests. Global cognitive function was evaluated using the Mini-Mental State Examination (MMSE). We defined dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) following the respective international criteria. Data were analyzed using multinomial logistic and general linear regression models.Results: Of all participants, 300 were diagnosed with dementia, including 195 with AD and 95 VaD. The multiple-adjusted odds ratio of dementia associated with quartiles of RDW were 1.45 (95%CI: 0.87–2.44), 1.00 (reference), 1.77 (1.07–2.93), and 2.28 (1.40–3.72). Similar J-shaped patterns existed for the association of RDW with odds ratio of AD and VaD. Anemia was not significantly associated with dementia. The J-shaped associations of RDW with dementia and subtypes were statistically evident only among participants without anemia. There was an inverted J-shaped relationship between RDW quartiles and β-coefficients of MMSE score.Conclusion: There is a J-shaped association between RDW level and likelihood of dementias among rural-dwelling Chinese older adults, especially among people without anemia.
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16.
  • Jiang, Ziying, et al. (författare)
  • Red cell distribution width, anemia, and lower-extremity physical function among rural-dwelling older adults
  • 2022
  • Ingår i: Aging Clinical and Experimental Research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 34:10, s. 2483-2491
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Elevated red cell distribution width (RDW) has been associated with degenerative conditions in aging.Aims We aimed to evaluate the associations of RDW and anemia with lower-extremity physical function among rural-dwelling older adults. Methods This population-based cross-sectional study included 5093 rural residents (age >= 60 years, 57.3% women) who participated in the MIND-China Study in Shandong. Data were collected via face-to-face interviews, clinical examinations, and laboratory tests. RDW was categorized according to quartiles and the lower-extremity physical function was assessed using the Short Physical Performance Battery (SPPB),Results Multiple linear regression analyses suggested that the fourth quartile of RDW (vs. first quartile) was associated with lower SPPB summary score (beta-coefficient - 0.38; 95% CI - 0.58 to - 0.18) and lower scores in balance test (- 0.09; - 0.17 to - 0.01), chair stand test (- 0.17; - 0.27 to - 0.07), and walking speed test (- 0.12; - 0.19 to - 0.05). Anemia was associated with a multiple-adjusted beta-coefficient of - 0.34 (- 0.52 to - 0.16) for SPPB summary score. Stratified analysis by anemia showed that there was a linear association between RDW and SPPB in individuals without anemia but a J-shaped association in individuals with anemia.Discussion This large-scale population-based study revealed the associations of high RDW and anemia with poor lower-extremity physical function among rural-dwelling Chinese older adults. These findings suggest that an elevated RDW might be a biochemical marker for poor lower-extremity physical function among older adults.Conclusions Anemia and an elevated RDW are associated with poor performance in lower-extremity physical function among rural-dwelling Chinese older adults.
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17.
  • Kivipelto, Miia, et al. (författare)
  • World-Wide FINGERS Network : A global approach to risk reduction and prevention of dementia
  • 2020
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:7, s. 1078-1094
  • Tidskriftsartikel (refereegranskat)abstract
    • Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.
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18.
  • Li, Yuanjing, et al. (författare)
  • Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education : A Population-Based Cohort Study 
  • 2023
  • Ingår i: Dementia and Geriatric Cognitive Disorders. - 1420-8008 .- 1421-9824. ; 52:4, s. 258-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. Methods: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. Results: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14–0.55) for dementia and 0.18 (0.07–0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60–74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38–0.69) for MCI and 0.46 (0.33–0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. Discussion: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education.
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19.
  • Li, Yuanjing, et al. (författare)
  • Characterizing Global and Regional Brain Structures in Amnestic Mild Cognitive Impairment Among Rural Residents : A Population-Based Study
  • 2021
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 80:4, s. 1429-1438
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Structural brain magnetic resonance imaging (MRI) scans may provide reliable neuroimaging markers for defining amnestic mild cognitive impairment (aMCI).Objective: We sought to characterize global and regional brain structures of aMCI among rural-dwelling older adults with limited education in China.Methods: This population-based study included 180 participants (aged >= 65 years, 42 with aMCI and 138 normal controls) in the Shandong Yanggu Study of Aging and Dementia during 2014-2016. We defined aMCI following the Petersen's criteria. Global and regional brain volumes were automatically segmented on MRI scans and compared using a region-of-interest approach. Data were analyzed using general linear regression models.Results: Multi-adjusted beta-coefficient (95% confidence interval) of brain volumes (cm(3)) associated with aMCI was -12.07 (-21.49, -2.64) for global grey matter (GM), -18.31 (-28.45, -8.17) for global white matter (WM), 28.17 (12.83, 44.07) for cerebrospinal fluid (CSF), and 2.20 (0.24, 4.16) for white matter hyperintensities (WMH). Furthermore, aMCI was significantly associated with lower GM volumes in bilateral superior temporal gyri, thalamus and right cuneus, and lower WM volumes in lateral areas extending from the frontal to the parietal, temporal, and occipital lobes, as well as right hippocampus (p < 0.05).Conclusion: Brain structure of older adults with aMCI is characterized by reduced global GM and WM volumes, enlarged CSF volume, increased WMH burden, reduced GM volumes in bilateral superior temporal gyri, thalamus, and right cuneus, and widespread reductions of lateral WM volumes.
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20.
  • Li, Yuanjing, et al. (författare)
  • Lifelong Cognitive Reserve, Imaging Markers of Brain Aging, and Cognitive Function in Dementia-Free Rural Older Adults : A Population-Based Study
  • 2023
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 92:1, s. 261-272
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cognitive reserve (CR) partly explains cognitive variability in the presence of pathological brain aging.Objective: We investigated the interplay of lifelong CR with age, sex, and brain aging markers in cognitive phenotypes among older adults with very limited education.Methods: This population-based cross-sectional study included 179 dementia-free participants (age ≥65 years; 39.7% women; 67.0% had no or elementary education) examined in 2014–2016. We assessed lacunes and volumes of hippocampus, ventricles, grey matter, white matter (WM), and white matter hyperintensities. Lifelong CR score was generated from six lifespan intellectual factors (e.g., education and social support). We used Mini-Mental State Examination (MMSE) score to assess cognition and Petersen’s criteria to define mild cognitive impairment (MCI). Data were analyzed using general linear and logistic models.Results: The association of higher lifelong CR score (range: –4.0–5.0) with higher MMSE score was stronger in women (multivariable-adjusted β-coefficient and 95% CI: 1.75;0.99–2.51) than in men (0.68;0.33–1.03) (pinteraction = 0.006). The association of higher CR with MCI (multivariable-adjusted odds ratio and 95% CI: 0.77;0.60–0.99) did not vary by age or sex. Among participants with low CR (<1.4[median]), greater hippocampal and WM volumes were related to higher MMSE scores with multivariable-adjusted β-coefficients being 1.77(0.41–3.13) and 0.44(0.15–0.74); the corresponding figures in those with high CR were 0.15(–0.76–1.07) and –0.17(–0.41–0.07) (pinteraction <0.01). There was no statistical interaction of CR with MRI markers on MCI.Conclusion: Greater lifelong CR capacity is associated with better late-life cognition among people with limited education, possibly by compensating for impact of neurodegeneration.
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21.
  • Liang, Xiaoyan, et al. (författare)
  • Association and interaction of TOMM40 and PVRL2 with plasma amyloid-β and Alzheimer's disease among Chinese older adults : a population-based study
  • 2022
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 113, s. 143-151
  • 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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22.
  • Liang, Xiaoyan, et al. (författare)
  • Exosomal miR-532-5p induced by long-term exercise rescues blood–brain barrier function in 5XFAD mice via downregulation of EPHA4
  • 2023
  • Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The breakdown of the blood–brain barrier, which develops early in Alzheimer's disease (AD), contributes to cognitive impairment. Exercise not only reduces the risk factors for AD but also confers direct protection against cognitive decline. However, the exact molecular mechanisms remain elusive, particularly whether exercise can liberate the function of the blood–brain barrier. Here, we demonstrate that long-term exercise promotes the clearance of brain amyloid-β by improving the function of the blood–brain barrier in 5XFAD mice. Significantly, treating primary brain pericytes or endothelial cells with exosomes isolated from the brain of exercised 5XFAD mice improves cell proliferation and upregulates PDGFRβ, ZO-1, and claudin-5. Moreover, exosomes isolated from exercised mice exhibit significant changes in miR-532-5p. Administration or transfection of miR-532-5p to sedentary mice or primary brain pericytes and endothelial cells reproduces the improvement of blood–brain barrier function. Exosomal miR-532-5p targets EPHA4, and accordingly, expression of EphA4 is decreased in exercised mice and miR-532-5p overexpressed mice. A specific siRNA targeting EPHA4 recapitulates the effects on blood–brain barrier-associated cells observed in exercised 5XFAD mice. Overall, our findings suggest that exosomes released by the brain contain a specific miRNA that is altered by exercise and has an impact on blood–brain barrier function in AD. 
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23.
  • Liang, Yajun, et al. (författare)
  • Metabolic syndrome in patients with first-ever ischemic stroke : prevalence and association with coronary heart disease
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The metabolic syndrome (MetS) has been well linked with coronary heart disease (CHD) in the general population, but studies have rarely explored their association among patients with stroke. We examine prevalence of MetS and its association with CHD in patients with first-ever ischemic stroke. This hospital-based study included 1851 patients with first-ever ischemic stroke (mean age 61.2 years, 36.5% women) who were hospitalized into two university hospitals in Shandong, China (January 2016–February 2017). Data were collected through interviews, physical examinations, and laboratory tests. MetS was defined following the National Cholesterol Education Program (NCEP) criteria, the International Diabetes Federation (IDF) criteria, and the Chinese Diabetes Society (CDS) criteria. CHD was defined following clinical criteria. Data were analyzed using binary logistic regression models. The overall prevalence of MetS was 33.4% by NECP criteria, 47.2% by IDF criteria, and 32.5% by CDS criteria, with the prevalence being decreased with age and higher in women than in men (p < 0.05). High blood pressure, high triglycerides, and low HDL-C were significantly associated with CHD (multi-adjusted odds ratio [OR] range 1.27–1.38, p < 0.05). The multi-adjusted OR of CHD associated with MetS defined by the NECP criteria, IDF criteria, and CDS criteria (vs. no MetS) was 1.27 (95% confidence interval 1.03–1.57), 1.44 (1.18–1.76), and 1.27 (1.03–1.57), respectively. In addition, having 1–2 abnormal components (vs. none) of MetS was associated with CHD (multi-adjusted OR range 1.66–1.72, p < 0.05). MetS affects over one-third of patients with first-ever ischemic stroke. MetS is associated with an increased likelihood of CHD in stroke patients.
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24.
  • Liu, Rui, et al. (författare)
  • Associations of sleep timing and time in bed with dementia and cognitive decline among Chinese older adults : A cohort study
  • 2022
  • Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 70:11, s. 3138-3151
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The longitudinal associations of sleep timing and time in bed (TIB) with dementia and cognitive decline in older adults are unclear.Methods: This population-based cohort study used data from 1982 participants who were aged >= 60 years, free of dementia, and living in rural communities in western Shandong, China. At the baseline (2014) and follow-up (2018) examinations, sleep parameters were assessed using standard questionnaires. Cognitive function was measured using the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the DSM-IV criteria, and the NIA-AA criteria for Alzheimer disease (AD). Data were analyzed using restricted cubic splines, Cox proportional-hazards models, and general linear models.Results: During the mean follow-up of 3.7 years, dementia was diagnosed in 97 participants (68 with AD). Restricted cubic spline curves showed J-shaped associations of sleep duration, TIB, and rise time with dementia risk, and a reverse J-shaped association with mid-sleep time. When sleep parameters were categorized into tertiles, the multivariable-adjusted hazard ratio (HR) of incident dementia was 1.69 (95%CI 1.01-2.83) for baseline sleep duration >8 hours (vs. 7-8 h), 2.17 (1.22-3.87) for bedtime before 9 p.m. (vs. 10 p.m. or later), and 2.00 (1.23-3.24) for mid-sleep time before 1 a.m. (vs. 1-1.5 a.m.). Early bedtime and mid-sleep time were significantly associated with incident AD (HR range: 2.25-2.51; p < 0.05). Among individuals who were free of dementia at follow-up, baseline long TIB, early bedtime and mid-sleep time, early and late rise time, and prolonged TIB and advanced bedtime and mid-sleep time from baseline to follow-up were associated with a greater decline in MMSE score (p < 0.05). These associations with cognitive decline were statistically evident mainly among men or participants who were aged 60-74 years.Conclusions: Long TIB and early sleep timing are associated with an increased risk of dementia, and the associations with greater cognitive decline are evident only among older people aged 60-74 years and men.
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25.
  • Liu, Rui, et al. (författare)
  • Self-reported sleep characteristics associated with dementia among rural-dwelling Chinese older adults : a population-based study
  • 2022
  • Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sleep characteristics associated with dementia are poorly defined and whether their associations vary by demographics and APOE genotype among older adults are unclear.Methods: This population-based cross-sectional study included 4742 participants (age ≥ 65 years, 57.1% women) living in rural China. Sleep parameters were measured using the self-rated questionnaires of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, and the National Institute on Aging-Alzheimer’s Association criteria for Alzheimer’s disease (AD). Data were analysed using multiple logistic and general linear regression models.Results: Dementia was diagnosed in 173 participants (115 with AD). Multivariable-adjusted odds ratio (OR) of dementia was 1.71 (95%CI, 1.07-2.72) for sleep duration ≤4 h/night (vs. > 6-8 h/night), 0.76 (0.49-1.18) for > 4-6 h/night, 1.63 (1.05-2.55) for > 8 h/night, 1.11 (1.03-1.20) for lower sleep efficiency (per 10% decrease), and 1.85 (1.19-2.89) for excessive daytime sleepiness. Very short sleep duration (≤4 h/night), lower sleep efficiency, and excessive daytime sleepiness were significantly associated with being diagnosed with AD (multivariable-adjusted OR range = 1.12-2.07; p < 0.05). The associations of sleep problems with dementia and AD were evident mainly among young-old adults (65-74 years) or APOE ε4 carriers. Among dementia-free participants, these sleep characteristics were significantly associated with a lower MMSE score.Conclusions: Self-reported sleep problems in dementia are characterized by very short or long sleep duration, low sleep efficiency, and excessive daytime sleepiness, especially among young-old people and APOE ε4 carriers.
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26.
  • Ma, Xiaotong, et al. (författare)
  • Association of sdLDL-C With Incident Carotid Plaques With Stable and Vulnerable Morphology : A Prospective Cohort Study
  • 2024
  • Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 55:3, s. 576-585
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) particles are more atherogenic than large and intermediate low-density lipoprotein cholesterol (LDL-C) subfractions. We sought to investigate the association of sdLDL-C and the sdLDL-C/LDL-C ratio with incident carotid plaques with stable and vulnerable morphology in rural China.METHODS: This community-based cohort study used data from the RICAS study (Rose Asymptomatic Intracranial Artery Stenosis), which enrolled 887 participants (aged ≥40 years) who were living in Kongcun Town, Pingyin County, Shandong, and free of carotid plaques and had no history of clinical stroke or transient ischemic attack at baseline (2017). Incident carotid plaques and their vulnerability were detected by carotid ultrasound at follow-up (2021). Multivariable logistic regression models were used to explore the association of sdLDL-C or sdLDL-C/LDL-C ratio with incident carotid plaques while adjusting for demographic factors, vascular risk factors, and follow-up time.RESULTS: Of the 887 participants (mean age [SD], 53.89 [8.67%] years; 54.34% women), 179 (20.18%) were detected with incident carotid plaques during an average follow-up of 3.94 years (SD=0.14). Higher sdLDL-C or sdLDL-C/LDL-C ratio, but not LDL-C, was significantly associated with an increased risk of incident carotid plaques. The upper tertile of sdLDL-C (versus lower tertile) was associated with the multivariate-adjusted odds ratio of 2.48 (95% CI, 1.00–6.15; P=0.049; P for linear trend=0.046) for carotid plaques with vulnerable morphology (n=41), and the association remained significant in participants with normal LDL-C (<130 mg/dL; n=693; upper versus lower tertile: odds ratio, 3.38 [95% CI, 1.15–9.90]; P=0.027; P for linear trend=0.025). Moreover, the sdLDL-C/LDL-C ratio was associated with a higher odds ratio of incident carotid plaques in participants without diabetes (P for interaction=0.014).CONCLUSIONS: Higher sdLDL-C was associated with an increased risk of incident carotid plaques, especially carotid plaques with vulnerable morphology, even in participants with normal LDL-C. This suggests the potential of sdLDL-C as a therapeutic target for stroke prevention.
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27.
  • Mao, Ming, et al. (författare)
  • Resting heart rate, cognitive function, and inflammation in older adults : a population-based study
  • 2023
  • Ingår i: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 35, s. 2821-2829
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Emerging evidence has linked elevated resting heart rate (RHR) with poor cognitive function in older adults, but the mechanisms underlying their association are poorly understood.Methods This population-based cross-sectional study included 4510 dementia-free participants (age >= 65 years; 56.9% females; 38.3% no formal education) in the baseline examination of the Multidomain Interventions to Delay Dementia and Disability in Rural China study. Of these, 1,386 had data on serum proinflammatory cytokines and adhesion molecules. RHR was measured using 12-lead electrocardiograph. We used the Mini-Mental State Examination (MMSE) and a neuropsychological test battery to assess cognitive function. Data were analyzed using the general linear and restricted cubic splines models.Results People with high RHR were more likely to have cardiometabolic diseases and worse cognitive function (p < 0.05). There was an inverted J-shaped association of RHR with MMSE and attention scores. Having RHR >= 80 bpm (vs. 60-69 bpm) was significantly associated with the multivariable-adjusted beta coefficients of - 0.58 [95% confidence interval (CI), - 1.00, - 0.16] for MMSE score and - 0.08 (- 0.15, - 0.01) for attention score. In the serum biomarker subsample, RHR was linearly associated with serum interleukin-6 (IL-6) (beta coefficient = 0.19; 95%CI 0.14, 0.24), IL-8 (0.08; 0.02, 0.13), IL-10 (0.09; 0.04, 0.15), tumor necrosis factor-alpha (0.06; 0.01, 0.11), monocyte chemotactic protein-1 (0.09; 0.04, 0.15), intercellular adhesion molecule-1 (0.16; 0.11, 0.22), and vascular cell adhesion molecule-1 (0.11; 0.06, 0.16).Conclusions There is an inverted J-shaped association of RHR with attention and global cognition. Poor cognitive function and high RHR may be linked through systemic low-grade inflammation and endothelial injury.
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28.
  • Mao, Ming, et al. (författare)
  • Ventricular Electrocardiographic Signatures Associated with Dementia and Plasma Alzheimer's Disease Biomarkers in Older Adults : A Population-Based Study
  • 2023
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 94:4, s. 1515-1526
  • 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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29.
  • Ren, Juan, et al. (författare)
  • Prevalence and associated factors of excessive daytime sleepiness in rural older adults : a population-based study
  • 2024
  • Ingår i: Sleep and Breathing. - 1520-9512 .- 1522-1709.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate the prevalence and associated factors of excessive daytime sleepiness (EDS) among rural-dwelling Chinese older adults.Methods We collected data on demographic, epidemiological, and clinical factors via in-person interviews and clinical examinations following a structured questionnaire. The 15-item Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms, the Berlin questionnaire (BQ) to assess obstructive sleep apnea (OSA) risk; and the Epworth Sleepiness Scale (ESS) to assess sleep characteristics. EDS was defined as the total ESS score > 10.Results This population-based study engaged 4845 participants (age ≥ 65 years, 57.3% female) in the 2018 examination of the Multimodal Interventions to Delay Dementia and Disability in Rural China. The prevalence of EDS was 9.3% in the total sample, 8.3% in females, and 10.6% in males, and the prevalence decreased with advanced age. Logistic regression analysis revealed that EDS was significantly associated with age (multivariable-adjusted odds ratio [OR] = 0.97; 95% confidence interval [CI] 0.95–0.99), female sex (0.53; 0.36–0.77), hypertension (0.68; 0.54–0.85), depressive symptoms (2.68; 2.07–3.46), high OSA risk (2.11; 1.69–2.63), and poor sleep quality (2.12; 1.60–2.82).Conclusion EDS affects nearly one-tenth of rural older adults in China. Older age, female sex, and hypertension were associated with a decreased likelihood of EDS, while depressive symptoms, high OSA risk, and poor sleep quality were correlated with an elevated likelihood of EDS.
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30.
  • Ren, Yifei, et al. (författare)
  • Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults : A population-based study
  • 2024
  • Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1550-1561
  • 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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31.
  • Ren, Yifei, et al. (författare)
  • Prevalence, Incidence, and Progression of Cognitive Impairment, No Dementia Among Rural-Dwelling Chinese Older Adults
  • 2022
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 85:4, s. 1583-1592
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Few studies have examined occurrence and progression of cognitive impairment, no dementia (CIND) in rural China.Objective: To determine the prevalence and incidence of CIND in rural-dwelling Chinese older adults, and to examine risk and protective factors associated with progression to CIND and dementia.Methods: This population-based study included 2,781 dementia-free participants (age≥65 years) who were examined at baseline (2014) and followed in 2018. Demographic, epidemiological, clinical, and neuropsychological data were collected following a structured questionnaire. We defined CIND according to subjective cognitive complaints and the age- and education-specific Mini-Mental State Examination (MMSE) score. Data were analyzed with the multinomial logistic regression models.Results: The overall prevalence of CIND was 10.54% and the incidence was 28.26 per 1,000 person-years. CIND at baseline was associated with the multi-adjusted odds ratio (OR) of 2.06 (95% confidence interval = 1.23–3.47) for incident dementia. Multinomial logistic regression analysis suggested that compared with no CIND, the multi-adjusted OR of incident CIND was 2.21 (1.51–3.23) for women and 0.62 (0.38–0.99) for high social support, whereas the multi-adjusted OR of incident dementia was 1.14 (1.09–1.18) for older age, 0.29 (0.16–0.53) for high education, and 2.91 (1.47–5.74) for having a stroke history.Conclusion: CIND affects over one-tenth of older adults living in rural communities of western Shandong province. People with CIND are twice as likely to progress to dementia as people without CIND. Female sex, low education, stroke history, and low social support are associated with an increased risk of progression from normal cognition to CIND or dementia.
  •  
32.
  • She, Rui, et al. (författare)
  • Comorbidity in patients with first-ever ischemic stroke : Disease patterns and their associations with cognitive and physical function
  • 2022
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study examined the prevalence and pattern of comorbidity among Chinese patients with first-ever acute ischemic stroke, and assessed the associations of specific comorbidity patterns with physical and cognitive functioning after stroke occurrence. A hospital-based cross-sectional study was conducted among 2,151 patients with first-ever ischemic stroke (age ≥40 years; 64.2% men) who were admitted to two university hospitals in Shandong, China between 2016 and 2017. Data on demographics, lifestyles, chronic health conditions, and use of medications were collected through in-person interviews, clinical examinations, and laboratory tests. Physical functioning was assessed by the Barthel index (BI) and the modified Rankin Scale (mRS) while cognitive functioning was assessed by the Montreal Cognitive Assessment test. The results showed that comorbidity was present in 90.9% of the stroke patients (women vs. men: 95.2 vs. 88.7%, P < 0.001). Exploratory factor analysis identified three patterns of comorbidity, i.e., patterns of degenerative-cardiopulmonary, heart-gastrointestinal-psychiatric, and metabolic-kidney diseases. The number of comorbidities was significantly associated with a higher likelihood of moderate-to-severe physical dependence [odds ratio (95% CI) = 1.15 (1.06-1.25) for BI and 1.12 (1.04-1.21) for mRS, all P < 0.01] and cognitive impairment [odds ratio (95% CI) = 1.11 (1.02-1.20), P = 0.017], after adjusting for multiple covariates. Almost all the three comorbidity patterns were associated with increased likelihoods of physical dependence (range for odds ratios: 1.26-1.33) and cognitive impairment (range for odds ratios: 1.25-1.34). No significant association was found between degenerative-cardiopulmonary pattern and mRS. These findings suggest that comorbidity is associated with poor physical and cognitive functioning during the acute phase of ischemic stroke. Routine assessments of comorbidity and cognitive and physical function among patients with acute ischemic stroke should be considered in stroke research and clinical practice.
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33.
  • She, Rui, et al. (författare)
  • Health-related quality of life after first-ever acute ischemic stroke : associations with cardiovascular health metrics
  • 2021
  • Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 30, s. 2907-2917
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose To investigate the associations between cardiovascular health (CVH) metrics and health-related quality of life (HRQL) among patients with ischemic stroke in China, and further explore the role of physical and cognitive function in their associations.Methods This hospital-based study included 1714 patients with first-ever acute ischemic stroke (age >= 40 years; 36.7% women) who were admitted to two university hospitals in Shandong, China. We collected information on seven CVH metrics (smoking, body mass index, diet, physical activity, blood pressure, total cholesterol, and fasting blood glucose) through interviews, clinical examinations, and laboratory tests. EQ-5D-3L was used to assess HRQL. Cognitive and physical functioning was assessed by the Montreal Cognitive Assessment test and Barthel index, respectively. Data were analyzed using the general linear regression models.Results The average score (SD) was 0.746 (0.23) for HRQL index and 72.7 (15.8) for self-rated health. Optimal levels of four individual CVH metric components (diet, physical activity, blood pressure, and blood glucose) and a higher composite CVH score were significantly associated with a greater HRQL index and better self-rated health (p < 0.05 for all). Physical dependence and cognitive impairment were associated with a lower HRQL index and poorer self-rated health status (p < 0.001). Furthermore, the relationships between CVH metrics and HRQL index varied by functional status, such that their associations were statistically significant only among people who had physical dependence or cognitive impairment.Conclusion Achieving a better cardiovascular health profile is associated with better quality of life among ischemic stroke survivors, primarily in those with physical or cognitive impairment.
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34.
  • Song, Lin, et al. (författare)
  • KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a
  • 2019
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Exosomes are nanosized membrane vesicles released from cells after fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) and play important roles in intercellular communication and numerous biological processes. However, the molecular mechanisms regulating exosome secretion remain poorly understood. Here we identify KIBRA as an adaptor-like protein that stabilizes Rab27a, which in turn controls exosome secretion both in vitro and in vivo. Knockdown or overexpression of KIBRA in neuronal and podocyte cell lines leads to a decrease or increase of exosome secretion, respectively, and KIBRA depletion increases MVB size and number. Comparing protein profiles between KIBRA knockout and wild-type mouse brain showed significantly decreased Rab27a, a small GTPase that regulates MVB-PM docking. Rab27a is stabilized by interacting with KIBRA, which prevents ubiquitination and degradation via the ubiquitin-proteasome pathway. In conclusion, we show that KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a.
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35.
  • Song, Lin, et al. (författare)
  • Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults : a population-based study
  • 2022
  • Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 33:7, s. 3664-3673
  • Tidskriftsartikel (refereegranskat)abstract
    • The kidney and brain expressed protein (KIBRA) rs17070145 polymorphism is associated with both structure and activation of the olfactory cortex. However, no studies have thus far examined whether KIBRA can be linked with olfactory function and whether brain structure plays any role in the association. We addressed these questions in a population-based cross-sectional study among rural-dwelling older adults. This study included 1087 participants derived from the Multidomain Interventions to Delay Dementia and Disability in Rural China, who underwent the brain MRI scans in August 2018 to October 2020; of these, 1016 took the 16-item Sniffin’ Sticks identification test and 634 (62.40%) were defined with olfactory impairment (OI). Data were analyzed using the voxel-based morphometry analysis and general linear, logistic, and structural equation models. The KIBRA rs17070145 C-allele (CC or CT vs. TT genotype) was significantly associated with greater gray matter volume (GMV) mainly in the bilateral orbitofrontal cortex and left thalamus (P < 0.05) and with the multi-adjusted odds ratio of 0.73 (95% confidence interval 0.56–0.95) for OI. The left thalamic GMV could mediate 8.08% of the KIBRA-olfaction association (P < 0.05). These data suggest that the KIBRA rs17070145 C-allele is associated with a reduced likelihood of OI among older adults, partly mediated through left thalamic GMV.
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36.
  • Tian, Na, et al. (författare)
  • Association of Triglyceride-Glucose Index With Cognitive Function and Brain Atrophy : A Population-Based Study
  • 2024
  • Ingår i: The American journal of geriatric psychiatry. - 1064-7481 .- 1545-7214. ; 32:2, s. 151-162
  • 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.
  •  
37.
  • Tian, Na, et al. (författare)
  • Triglyceride-glucose index, Alzheimer's disease plasma biomarkers, and dementia in older adults : The MIND-China study
  • 2023
  • Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - 2352-8729. ; 15:2
  • 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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38.
  • Wang, Chaoqun, et al. (författare)
  • Associations of Cardiac Ventricular Repolarization with Serum Adhesion Molecules and Cognitive Function in Older Adults : The MIND-China Study
  • 2023
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 92:1, s. 273-283
  • 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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39.
  • Wang, Chaoqun, et al. (författare)
  • Associations of WWC1 variants with Alzheimer?s disease and vascular dementia among rural older adults in China : A population-based study
  • 2023
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 125, s. 109-114
  • Tidskriftsartikel (refereegranskat)abstract
    • We sought to examine the associations of common WWC1 variants with Alzheimer's disease (AD) and vascular dementia (VaD) among rural-dwelling older adults in China. This population-based study used data from the baseline assessments (March –September 2018) of MIND-China. AD and VaD were diagnosed following the international criteria. Of the 5455 participants (age≥60 years, 57.27% women), 182 were diagnosed with AD and 88 with VaD. Logistic regression analysis suggested that WWC1 rs17070145 C allele (vs. T) was associated with multivariable-adjusted odds ratio of 1.23 (95% confidence interval 0.96–1.58) for AD, and that CC genotype (vs. TT) was associated with multivariable-adjusted odds ratio of 2.19(1.10–4.39) for VaD, but the association with VaD became non-significant when further adjusting for stroke history. Furthermore, exonic SNPs rs3822660 and rs3822659 were in strong linkage disequilibrium (LD) with rs17070145 (D’ = 0.88). These results suggest that the strong LD between rs17070145 and 2 exonic SNPs may explain the association of WWC1 rs17070145 C allele with AD and that stroke may partly explain the association of WWC1 rs17070145 CC genotype with VaD.
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40.
  • Wang, Mingqi, et al. (författare)
  • High-density lipoprotein cholesterol and brain aging amongst rural-dwelling older adults : a population-based magnetic resonance imaging study
  • 2021
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:9, s. 2882-2892
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Current evidence supports the involvement of lipids in brain aging. A range of serum lipids is explored in association with brain structure and cognitive function amongst rural-dwelling older adults.Methods: This population-based cross-sectional study included 184 rural-dwelling adults (age ≥ 65 years, 39.1% women) in Shandong, China. In 2014–2016, data on demographics, lifestyle, health conditions and serum lipids were collected. Volumes of gray matter, white matter, ventricles, hippocampus and white matter hyperintensity were automatically estimated on brain magnetic resonance imaging. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE), and mild cognitive impairment (MCI) was defined according to Petersen's criteria. Data were analyzed using the general linear regression, logistic regression and mediation models.Results: Of the 184 participants, 47 were defined with MCI. Low high-density lipoprotein cholesterol (HDL-C; <1.55 vs. ≥1.55 mmol/l) was significantly associated with reduced volumes of total white matter (multi-adjusted β = −9.77, 95% confidence interval −19.48–0.06) and hippocampus (−0.23, −0.46–0.01), a lower MMSE score (−1.49, −2.67–0.31) and a higher likelihood of MCI (multi-adjusted odds ratio 3.21, 95% confidence interval 1.42–7.29). The mediation effects of structural brain measures on the associations between a low level of HDL-C and MMSE score or MCI were not statistically significant (p > 0.05).Conclusions: This study suggests that low HDL-C may be involved in structural brain aging and cognitive dysfunction amongst rural-dwelling older adults in China, but the association of low HDL-C with cognitive aging phenotypes appears not to be mediated by brain structure.
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41.
  • Wang, Pin, et al. (författare)
  • Comparing glycemic traits in defining diabetes among rural Chinese older adults
  • 2024
  • Ingår i: PLOS ONE. - 1932-6203. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWe sought to identify the optimal cut-off of glycated hemoglobin (HbA1c) for defining diabetes and to assess the agreements of fasting plasma glucose (FPG), fasting serum glucose (FSG), and HbA1c in defining diabetes among rural older adults in China.MethodsThis population-based cross-sectional study included 3547 participants (age ≥61 years, 57.8% women) from the Multidomain Interventions to Delay Dementia and Disability in Rural China from 2018–2019; of these, 3122 had no previously diagnosed diabetes. We identified the optimal cut-off of HbA1c against FPG ≥7.0 mmol/L for defining diabetes by using receiver operating characteristic curve and Youden index. The agreements of FPG, FSG, and HbA1c in defining diabetes were assessed using kappa statistics.ResultsAmong participants without previously diagnosed diabetes (n = 3122), the optimal HbA1c cut-off for defining diabetes was 6.5% (48 mmol/mol), with the sensitivity of 88.9%, specificity of 93.7%, and Youden index of 0.825. The correlation coefficients were 0.845 between FPG and FSG, 0.574 between FPG and HbA1c, and 0.529 between FSG and HbA1c in the total sample (n = 3547). The kappa statistic for defining diabetes was 0.962 between FSG and FPG, and 0.812 between HbA1c and FPG.ConclusionsThe optimal cut-off of HbA1c for diagnosing diabetes against FPG >7.0 mmol/L is ≥6.5% in Chinese rural-dwelling older adults. The agreement in defining diabetes using FPG, FSG, and HbA1c is nearly perfect. These results have relevant implications for diabetes research and clinical practice among older adults in China.
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42.
  • Wang, Shaoying, et al. (författare)
  • Characterizing lipid profiles associated with asymptomatic intracranial arterial stenosis in rural-dwelling adults : A population-based study
  • 2020
  • Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874 .- 1876-4789. ; 14:3, s. 371-380
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although individual lipid parameters have been frequently examined in association with asymptomatic intracranial arterial stenosis (aICAS), few population-based studies have investigated the lipid profiles associated with aICAS among Chinese adults. OBJECTIVE: This study aims to characterize the lipid profiles associated with aICAS in rural-dwelling adults in China. METHODS: This population-based study included 2027 persons who were aged >= 40 years and free of stroke. Data were collected via interviews, clinical examinations, and laboratory testing. We diagnosed aICAS by integrating transcranial color Doppler with magnetic resonance angiography. Data were analyzed using binary and multinomial logistic regression models. RESULTS: Of the 2027 participants, 154 were detected with aICAS. The multiadjusted odds ratio (95% confidence interval) of aICAS was 1.41 (0.997-2.00) for high small dense low-density lipoprotein cholesterol, 1.44 (1.02-2.04) for high lipoprotein(a), 1.71 (1.21-2.44) for low apolipoprotein A-1, 1.43 (1.00-2.04) for low high-density lipoprotein cholesterol (HDL-C), 1.61 (1.14-2.27) for high apolipoprotein B/apolipoprotein A-1 ratio, 1.95 (1.38-2.76) for high low-density lipoprotein cholesterol/HDL-C ratio, and 1.51 (1.06-2.14) for high total cholesterol/HDL-C ratio. When severity of aICAS was analyzed, high levels of lipoprotein(a), small dense low-density lipoprotein cholesterol, and lipid ratios were significantly associated with an increased likelihood of moderate-to-severe aICAS (P < .05). An increasing number of abnormal lipid measurements was associated with an increased likelihood of aICAS (P for trend <.001). CONCLUSION: These findings suggest that lipid profiles for aICAS among rural residents in China are characterized by high atherogenic cholesterol, low antiatherogenic cholesterol, and high ratios of atherogenic-to-antiatherogenic cholesterol or lipoproteins.
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43.
  • Wang, Shanshan, et al. (författare)
  • Differential Associations of 6 Adiposity Indices With Dementia in Older Adults : The MIND-China Study
  • 2023
  • Ingår i: Journal of the American Medical Directors Association. - 1525-8610 .- 1538-9375. ; 24:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The cross-sectional association between late-life obesity and dementia is often explained by the obesity paradox. We assessed the potential differential associations of various adiposity indices with dementia and subtypes of dementia in rural Chinese older adults.Design: A population-based cross-sectional study.Setting and Participants: A total of 5277 participants (age ≥60 years; 57.23% female) who were living in rural communities and were examined in March–September 2018 for MIND-China.Methods: We used weight, height, and waist circumference (WC) to calculate 6 adiposity indices: body mass index (BMI), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), A Body Shape Index (ABSI), body roundness index (BRI), and Conicity Index (ConI). Dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were clinically diagnosed following the international criteria. Data were analyzed with logistic regression models.Results: Of the 5277 participants, 303 were diagnosed with dementia, including 193 with AD and 99 with VaD. The multivariable-adjusted odds ratio (95% CI) of dementia associated with the highest (vs lowest) quintile of adiposity index was 2.32 (1.40–3.85) for WWI, 1.56 (1.03–2.36) for ABSI, and 1.40 (0.92–2.11) for ConI. Similarly, higher levels of these 3 adiposity indices were significantly associated with an increased likelihood of AD, whereas a higher BMI was associated with a decreased likelihood of AD. None of the 6 examined adiposity indices was significantly associated with VaD when adjusting for multiple confounders.Conclusions and Implications: The adiposity index WWI is linearly associated with the likelihood of dementia and AD. An increased WWI may be a clinical marker for the dementia syndrome and Alzheimer's dementia.
  •  
44.
  • Wang, Yongxiang, et al. (författare)
  • Health status and risk profiles for brain aging of rural‐dwelling older adults : Data from the interdisciplinary baseline assessments in MIND‐China
  • 2022
  • Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 8:1
  • 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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45.
  • Wang, Yongxiang, et al. (författare)
  • Lifespan Intellectual Factors, Genetic Susceptibility, and Cognitive Phenotypes in Aging : Implications for Interventions
  • 2019
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 11
  • Forskningsöversikt (refereegranskat)abstract
    • Along with rapid global population aging, the age-related cognitive disorders such as mild cognitive impairment (MCI) and dementia have posed a serious threat to public health, health care system, and sustainable economic and societal development of all countries. In this narrative review, we seek to summarize the major epidemiological studies from the life-course perspective that investigate the influence of genetic susceptibility [e.g., apolipoprotein (APOE) epsilon 4 allele] and intellectual or psychosocial factors (e.g., educational attainments and leisure activities) as well as their interactions on cognitive phenotypes in aging. Numerous population-based studies have suggested that early-life educational attainments and socioeconomic status, midlife work complexity and social engagements, late-life leisure activities (social, physical, and mentally-stimulating activities), certain personality traits (e.g., high neuroticism and low conscientiousness), and depression significantly affect late-life cognitive phenotypes. Furthermore, certain intellectual or psychosocial factors (e. g., leisure activities and depression) may interact with genetic susceptibility (e.g., APOE epsilon 4 allele) to affect the phenotypes of cognitive aging such that risk or beneficial effects of these factors on cognitive function may vary by carrying the susceptibility genes. Current evidence from the randomized controlled trials that support the cognitive benefits of cognitive training among cognitive healthy older adults remains limited. The cognitive reserve hypothesis has been proposed to partly explain the beneficial effects of lifetime intellectual and psychosocial factors on late-life cognitive function. This implies that, from a life-course perspective, preventive intervention strategies targeting multiple modifiable intellectual and psychosocial factors could interfere with clinical expression of cognitive disorders in old age and delay the onset of dementia syndrome, and thus, may help achieve healthy brain aging.
  •  
46.
  • Wang, Yongxiang, et al. (författare)
  • Nonalcoholic fatty liver disease, serum cytokines, and dementia among rural-dwelling older adults in China : A population-based study
  • 2022
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:9, s. 2612-2621
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Little is known about whether nonalcoholic fatty liver disease (NAFLD) is associated with dementia or the role of serum proinflammatory cytokines in the association. We aimed to investigate the interrelationships of NAFLD, serum cytokines, and dementia among rural-dwelling older adults.Methods: This population-based cross-sectional study included 5129 participants (aged ≥60 years; 61.79% women) who were living in rural communities and examined in March 2018–September 2018. NAFLD was defined through transabdominal ultrasound examination in the absence of hepatitis B or excessive alcohol consumption. Serum cytokines were measured in a subsample (n = 1686). Dementia, Alzheimer disease (AD), and vascular dementia (VaD) were diagnosed following international criteria. Data were analyzed with logistic regression and mediation models.Results: Of the 5129 participants, 455 (8.87%) were detected with moderate-to-severe NAFLD, and 292 (5.69%) were diagnosed with dementia (188 with AD and 96 with VaD). The multivariable adjusted odds ratios associated with moderate-to-severe (vs. no-to-mild) NAFLD were 2.22 (95% confidence interval [CI] = 1.41–3.49) for all-cause dementia, 1.88 (95% CI = 1.01–3.50) for AD, and 2.62 (95% CI = 1.33–5.17) for VaD. In the cytokine subsample, controlling for multiple potential confounders, moderate-to-severe NAFLD was significantly associated with higher levels of serum monocyte chemotactic protein-1, interleukin-17A, interleukin-6 (IL-6), interleukin-8, and tumor necrosis factor-α (P < 0.05). The mediation analysis showed that IL-6 mediated 12.56% of the association between NAFLD and VaD.Conclusions: Moderate-to-severe nonalcoholic fatty liver disease is associated with dementia and AD, especially with VaD, among rural-dwelling Chinese older adults, in which the association with VaD is partly mediated by serum inflammatory cytokines.
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47.
  • Wang, Yongxiang, et al. (författare)
  • Objectively-measured movement behaviors, systemic low-grade inflammation, and plasma neurofilament light chain in older adults : a population-based study
  • 2023
  • Ingår i: Immunity & Ageing. - 1742-4933. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundEvidence has linked self-reported sedentary behavior (SB) and physical activity (PA) with cognitive impairment; however, the underlying mechanisms are poorly understood. We examined the associations of the accelerometer-measured movement behaviors with plasma neurofilament light chain (NfL) among older adults and the role of systemic low-grade inflammation in the associations.ResultsThis population-based study included 1,029 dementia-free older adults (age & GE; 60 years, range 60-88 years; 59.48% women) who undertook the ActiGraph substudy (March 2018-December 2020) in MIND-China. There were nonlinear relationships of daily SB and PA time with plasma NfL concentration, such that more daily SB time or less time spent in daily light-intensity physical activity (LPA) and moderate-to-vigorous-intensity physical activity (MVPA) was significantly associated with increased plasma NfL only when SB time & GE; 8.00 h/day or LPA time < 5.00 h/day or MVPA time < 2.00 h/day. Furthermore, more daily SB time or less daily LPA and MVPA time was significantly associated with higher serum low-grade inflammation score, a composite measure generated from serum IL-6, IL-8, TNF-& alpha;, and ICAM-1 (P < 0.05). Finally, low-grade inflammation score accounted for 14.5% to 17.8% of the associations between movement behaviors and plasma NfL.ConclusionsMore daily SB and less PA time are associated with neurodegeneration and systemic low-grade inflammation in older adults. The association of movement behaviors with neurodegeneration is partially mediated by low-grade inflammation.
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48.
  • Xu, Zhe, et al. (författare)
  • Associations of macular microvascular parameters with cerebral small vessel disease in rural older adults : A population-based OCT angiography study
  • 2023
  • Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To explore the associations of macular microvascular parameters with cerebral small vessel disease (CSVD) in rural-dwelling older adults in China.Methods: This population-based cross-sectional study included 195 participants (age ≥ 60 years; 57.4% women) in the optical coherence tomographic angiography (OCTA) sub-study within the Multimodal Interventions to delay Dementia and disability in rural China (MIND-China). Macular microvascular parameters were measured using the OCTA. We automatically estimated volumes of gray matter, white matter, and white matter hyperintensity (WMH), and manually assessed numbers of enlarged perivascular spaces (EPVS) and lacunes on brain magnetic resonance imaging. Data were analyzed with the general linear models.Results: Adjusting for multiple confounders, lower vessel skeleton density (VSD) and higher vessel diameter index (VDI) were significantly associated with larger WMH volume (P < 0.05). Lower VSD and foveal density-300 (FD-300) of left eye were significantly associated with lower brain parenchymal volume (P < 0.05). In addition, lower areas of foveal avascular zone (FAZ) and FD-300 of left eye were significantly associated with more EPVS (P < 0.05). The associations of abnormal macular microvascular parameters with WMH volume were evident mainly among females. Macular microvascular parameters were not associated with lacunes.Conclusion: Macular microvascular signs are associated with WMH, brain parenchymal volume, and EPVS in older adults. The OCTA-assessed macular microvascular parameters can be valuable markers for microvascular lesions in the brain.
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49.
  • Yin, Qingqing, et al. (författare)
  • Targetting Exosomes as a New Biomarker and Therapeutic Approach for Alzheimer's Disease
  • 2020
  • Ingår i: Clinical Interventions in Aging. - 1176-9092 .- 1178-1998. ; 15, s. 195-205
  • Forskningsöversikt (refereegranskat)abstract
    • Alzheimer's disease (AD) is a neurodegenerative disease that mainly occurs in old age and involves progressive cognitive impairment. AD has become a major global issue for public health, with approximately 24 million people currently affected by the disease. Estimates indicted that this number will quadruple by 2050. Because of the high incidence of AD, there is an urgent need to develop new strategies to diagnose and treat AD. Many recent studies have indicated the multiple, yet somewhat controversial, roles of exosomes in AD. Although the underlying mechanisms by which exosomes play a role in AD are still unknown, current evidence suggests that exosomes can carry and spread toxic amyloid-beta, and hyperphosphorylated tau, between cells, and then induce apoptosis, thus contributing to the loss of neurons. In addition, exosomes appear to possess the ability to reduce brain amyloid-beta, and tau hyperphosphorylation, and transfer neuroprotective substances between neural cells. The accumulating data brings hope that the application of exosomes may be helpful for early diagnostics and the identification of new therapeutic targets for AD. Here, we summarized the various roles of exosomes, and how they might relate to the pathogenesis of AD. We also highlight the potential application of exosomes as a therapeutic option in AD therapy.
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50.
  • Zhang, Cong, et al. (författare)
  • Association of Metabolic Syndrome with Macular Thickness and Volume in Older Adults : A Population-Based Optical Coherence Tomography Study
  • 2024
  • Ingår i: Metabolic Syndrome and Related Disorders. - 1540-4196 .- 1557-8518. ; 22:2, s. 141-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To explore the associations of the metabolic syndrome (MetS) and individual components with macular thickness and volume among rural-dwelling Chinese older adults.Methods: This population-based cross-sectional study included 705 participants (age ≥60 years) derived from the MIND-China study. In 2018–2019, we collected data through face-to-face interview, clinical examination, optical coherence tomography (OCT) examination, and blood test. We measured macular thickness and volume using spectral-domain OCT. MetS was defined following the International Diabetes Federation (IDF) criteria, the IDF/American Heart Association (AHA) criteria, the National Cholesterol Education Program-Adult Treatment Panel III criteria, and the Chinese Diabetes Society (CDS) criteria. Data were analyzed with multivariable general linear models.Results: MetS was significantly associated with thinner macula in central (multivariable-adjusted β = −5.29; 95% confidence interval: −9.31 to −1.26), parafoveal (−2.85; −5.73 to 0.04) and perifoveal regions (−4.37; −6.79 to −1.95) when using the IDF criteria, in the perifoveal regions (−3.82; −6.18 to −1.47) when using the IDF/AHA criteria, and in the central region (−5.63; −10.25 to −1.02) when using the CDS criteria, and with reduced macular volume when using the IDF (−0.16; −0.26 to −0.07) and IDF/AHA (−0.13; −0.22 to −0.04) criteria. In the parafoveal region, the IDF-defined MetS was significantly associated with thinner retina in men (β = −6.25; −10.94 to −1.56) but not in women. Abdominal obesity (−2.83; −5.41 to −0.25) and elevated fasting blood glucose (−2.65; −5.08 to −0.21) were associated with thinner macular thickness in the perifoveal region.Conclusion: MetS is associated with macular thinning and reduced macular volume among rural-dwelling older adults, and the associations vary by the defining criteria of MetS.
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