Association of sdLDL-C With Incident Carotid Plaques With Stable and Vulnerable Morphology: A Prospective Cohort Study.

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. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017197.

Strategic Lacunes Associated With Mild Cognitive Impairment in Rural Chinese Older Adults: A Population-Based Study.

BACKGROUND: Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. METHODS: This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. RESULTS: Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. CONCLUSIONS: Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.

Association of Triglyceride-Glucose Index With Cognitive Function and Brain Atrophy: A Population-Based Study.

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.

Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults: a population-based study.

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.

Prevalence and associated factors of excessive daytime sleepiness in rural older adults: a population-based study.

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.

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population-based study.

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 (Aß), 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 Aß 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. HIGHLIGHTS: We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

Association of Accelerometer-Measured Sedentary Behavior Patterns With Nonalcoholic Fatty Liver Disease Among Older Adults: The MIND-China Study.

INTRODUCTION: The relationships between sedentary behavior patterns and nonalcoholic fatty liver disease (NAFLD) in older adults are not well investigated. METHODS: This population-based study included 1,899 rural-dwelling adults (aged 60 years or older). We assessed sedentary parameters with ActiGraph and defined NAFLD using ultrasonography. RESULTS: Long total and prolonged sedentary time were associated with increased likelihoods of NAFLD, whereas engaging more breaks per sedentary hour and reallocating sedentary time to light-intensity physical activity were associated with reduced likelihoods of NAFLD (P linear <0.05). DISCUSSION: Shorter sedentary time, engaging more frequent breaks in sedentary behavior, and replacing sedentary time with physical activity are associated with reduced likelihoods of NAFLD in older adults.

Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education: A Population-Based Cohort Study.

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.

Objectively-measured movement behaviors, systemic low-grade inflammation, and plasma neurofilament light chain in older adults: a population-based study.

BACKGROUND: Evidence 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. RESULTS: This population-based study included 1,029 dementia-free older adults (age ≥ 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 ≥ 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-α, 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. CONCLUSIONS: More 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.

Resting heart rate, cognitive function, and inflammation in older adults: a population-based study.

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 ß 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) (ß 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-α (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.

Mild cognitive impairment among rural-dwelling older adults in China: A community-based study.

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) ε4 allele (vs ε3/ε3). 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.

Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults.

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 (Aß)40, Aß42, 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.

Nonalcoholic fatty liver disease, serum cytokines, and dementia among rural-dwelling older adults in China: A population-based study.

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.

Predictors for symptomatic intracranial hemorrhage after intravenous thrombolysis with acute ischemic stroke within 6 h in northern China: a multicenter, retrospective study.

BACKGROUND AND PURPOSE: This study assessed the predictive factors for symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke (AIS) after receiving intravenous thrombolysis (IVT) within 6 h in northern China. METHODS: We retrospectively analyzed ischemic stroke patients who were treated with IVT between November 2016 and December 2018 in 19 hospitals in Shandong Province, China. Potential predictors of sICH were investigated using univariate and multivariate analyses. RESULTS: Of the 1293 enrolled patients (845 men, aged 62 ± 11 years), 33 (2.6%) developed sICH. The patients with sICH had increased coronary heart disease (36.4% vs. 13.7%, P = 0.001), more severe stroke (mean National Institutes of Health Stroke Scale [NIHSS] score on admission of 14 vs.7, P < 0.001), longer door-to-needle time [DNT] (66 min vs. 50 min, P < 0.001), higher blood glucose on admission, higher white blood cell counts (9000/mm3 vs. 7950/mm3, P = 0.004) and higher neutrophils ratios (73.4% vs. 67.2%, P = 0.006) et al. According to the results of multivariate analysis, the frequency of sICH was independently associated with the NIHSS score (OR = 3.38; 95%CI [1.50-7.63]; P = 0.003), DNT (OR = 4.52; 95%CI [1.69-12.12]; P = 0.003), and white blood cell count (OR = 3.59; 95%CI [1.50-8.61]; P = 0.004). When these three predictive factors were aggregated, compared with participants without any factors, the multi-adjusted odds ratios (95% confidence intervals) of sICH for persons concurrently having one, two or three of these factors were 2.28 (0.25-20.74), 15.37 (1.96-120.90) and 29.05 (3.13-270.11), respectively (P for linear trend < 0.001), compared with participants without any factors. CONCLUSION: NIHSS scores higher than 10 on admission, a DNT > 50 min, and a white blood cell count ≥9000/mm3 were independent risk factors for sICH in Chinese patients within 6 h after IVT for AIS.

Self-reported sleep characteristics associated with dementia among rural-dwelling Chinese older adults: a population-based study.

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. TRIAL REGISTRATION: ChiCTR1800017758 (Aug 13, 2018).

Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study.

Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer's disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer's disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer's disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10-19, 2.49 × 10-23, 1.35 × 10-67, and 4.81 × 10-9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P < 5.0 × 10-8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer's disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer's disease, suggesting that our models can predict Alzheimer's disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer's disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer's disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.

Red cell distribution width, anemia, and lower-extremity physical function among rural-dwelling older adults.

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 (ß-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 ß-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.

Accelerometer-assessed sedentary behaviour among Chinese rural older adults: Patterns and associations with physical function.

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.

Association Between Intracranial Pulsatility and White Matter Hyperintensities in Asymptomatic Intracranial Arterial Stenosis: A Population-Based Study in Shandong, China.

OBJECTIVES: The effects of increased intracranial pulsatility on the severity of white matter hyperintensities (WMH) in participants with asymptomatic intracranial arterial stenosis (aICAS) remain uncertain. We aimed to investigate whether an increased pulsatility index (PI) is associated with WMH volume (WMHV) in individuals with aICAS. MATERIALS AND METHODS: All participants were recruited from the Kongcun Town aICAS Study, including a total of 103 participants with aICAS and 98 healthy controls (age- and sex-matched). PI was assessed using transcranial Doppler ultrasound. The WMHV was calculated through the lesion segmentation tool system for the Statistical Parametric Mapping package based on magnetic resonance imaging. The association between PI and lnWMHV was analyzed by linear regression models adjusting for demographics, lifestyle, and vascular risk factors. RESULTS: The lnWMHV and PI between the aICAS and control groups showed no significant differences (P = 0.171 and 0.287, respectively). In a multivariable model, age ≥ 60 years and male sex (P = 0.000 and 0.006, respectively) were significant predictors of lnWMHV in the aICAS group. In sex-stratified analyses, there was a significant association between PI and lnWMHV in males with aICAS (P = 0.038). CONCLUSIONS: This study suggest there might be a likely association between increased intracranial pulsatility and WMH burden in males with aICAS.