| 1. |
- Dong, Yi, et al.
(author)
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Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults
- 2023
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:2, s. 589-601
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Journal article (peer-reviewed)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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| 2. |
- Han, Xiaolei, et al.
(author)
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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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In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 96:2, s. 657-668
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Journal article (peer-reviewed)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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| 3. |
- Li, Yuanjing, et al.
(author)
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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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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 92:1, s. 261-272
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Journal article (peer-reviewed)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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| 4. |
- Li, Yuanjing, et al.
(author)
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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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In: Dementia and Geriatric Cognitive Disorders. - 1420-8008 .- 1421-9824. ; 52:4, s. 258-266
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Journal article (peer-reviewed)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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| 5. |
- Luo, Yifei, et al.
(author)
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Technology Roadmap for Flexible Sensors
- 2023
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In: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
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Research review (peer-reviewed)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 6. |
- Song, Lin, et al.
(author)
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Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults : a population-based study
- 2022
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In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 33:7, s. 3664-3673
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Journal article (peer-reviewed)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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| 7. |
- Wang, Mingqi, et al.
(author)
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High-density lipoprotein cholesterol and brain aging amongst rural-dwelling older adults : a population-based magnetic resonance imaging study
- 2021
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:9, s. 2882-2892
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Journal article (peer-reviewed)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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| 8. |
- Wang, Yongxiang, et al.
(author)
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Health status and risk profiles for brain aging of rural‐dwelling older adults : Data from the interdisciplinary baseline assessments in MIND‐China
- 2022
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In: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 8:1
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Journal article (peer-reviewed)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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| 9. |
- Wang, Yongxiang, et al.
(author)
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Nonalcoholic fatty liver disease, serum cytokines, and dementia among rural-dwelling older adults in China : A population-based study
- 2022
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:9, s. 2612-2621
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Journal article (peer-reviewed)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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| 10. |
- Dong, Yi, et al.
(author)
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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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In: JOURNAL OF ALZHEIMERS DISEASE. - 1387-2877 .- 1875-8908. ; 96:2, s. 845-858
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Journal article (peer-reviewed)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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