| 1. |
- Cong, Lin, et al.
(författare)
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Mild cognitive impairment among rural-dwelling older adults in China : A community-based study
- 2023
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:1, s. 56-66
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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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| 2. |
- Dong, Yi, et al.
(författare)
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Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults
- 2023
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:2, s. 589-601
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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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| 3. |
- Dong, Yi, et al.
(författare)
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Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer's Disease Clinical Spectrum: A Population-Based Study
- 2023
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Ingår i: JOURNAL OF ALZHEIMERS DISEASE. - 1387-2877 .- 1875-8908. ; 96:2, s. 845-858
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Tidskriftsartikel (refereegranskat)abstract
- Background: Plasma biomarkers have emerged as a promising approach for characterizing pathophysiology in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Objective: We aimed to characterize plasma biomarkers for AD and neurodegeneration across the AD clinical continuum, and to assess their ability to differentiate between AD, MCI, and normal cognition. Methods: This population-based study engaged 1,446 rural-dwelling older adults (age >= 60 years, 61.0% women) derived from MIND-China; of these, 402 were defined with MCI and 142 with AD. Plasma amyloid-beta (A beta), total tau (t-tau), and neurofilament light chain (NfL) concentrations were analyzed using the Simoa platform. Data were analyzed using linear and logistic regression models, and receiver operating characteristic (ROC) analysis. Results: Across the AD clinical spectrum, plasma A beta(40) and NfL increased, whereas A beta(42)/A beta(40) ratio decreased. Plasma t-tau was higher in people withADdementia than those with MCI or normal cognition. Plasma NfL outperformed other biomarkers in differentiating AD from normal cognition (area under the ROC curve [AUC] = 0.75), but all plasma biomarkers performed poorly to distinguish MCI from normal cognition (AUC <0.60). Plasma NfL in combination with age, sex, education, and APOE genotype yielded the AUC of 0.87 for differentiating between AD and normal cognition, 0.79 between AD and MCI, and 0.64 between MCI and normal cognition. Conclusions: In this Chinese population, AD plasma biomarkers vary by age, sex, and APOE genotype. Plasma A beta, t-tau, and NfL differ across the AD clinical spectrum, and plasma NfL appears to be superior to plasma A beta and t-tau for defining the clinical spectrum.
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| 4. |
- Fa, Wenxin, et al.
(författare)
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Associations of Blood Absolute Neutrophil Count and Cytokines With Cognitive Function in Dementia-Free Participants : A Population-Based Cohort Study
- 2023
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1079-5006 .- 1758-535X.
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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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| 5. |
- Fan, Dong, et al.
(författare)
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Cardiovascular health profiles, systemic inflammation, and physical function in older adults : A population-based study
- 2023
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 109
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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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| 6. |
- Han, Xiaolei, et al.
(författare)
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Accelerometer-measured sedentary behavior patterns, brain structure, and cognitive function in dementia-free older adults : a population-based study
- 2023
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 96:2, s. 657-668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood.Objective: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms.Methods: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018-2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models.Results: In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (ptrend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores.Conclusion: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association.
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| 7. |
- Li, Yuanjing, et al.
(författare)
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Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education : A Population-Based Cohort Study
- 2023
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Ingår i: Dementia and Geriatric Cognitive Disorders. - 1420-8008 .- 1421-9824. ; 52:4, s. 258-266
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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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| 8. |
- Li, Yuanjing, et al.
(författare)
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Lifelong Cognitive Reserve, Imaging Markers of Brain Aging, and Cognitive Function in Dementia-Free Rural Older Adults : A Population-Based Study
- 2023
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 92:1, s. 261-272
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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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| 9. |
- Liang, Xiaoyan, et al.
(författare)
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Exosomal miR-532-5p induced by long-term exercise rescues blood–brain barrier function in 5XFAD mice via downregulation of EPHA4
- 2023
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Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 22:1
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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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| 10. |
- Mao, Ming, et al.
(författare)
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Resting heart rate, cognitive function, and inflammation in older adults : a population-based study
- 2023
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Ingår i: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 35, s. 2821-2829
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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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