Association between the triglyceride-glucose index and cognitive impairment in China: a community population-based cross-sectional study.

INTRODUCTION: Insulin resistance (IR) is a feature of metabolic syndrome and plays an important role in cognitive impairment (CI). The triglyceride-glucose (TyG) index is a convenient and cost-effective surrogate for assessing IR. This study aimed to assess the association between the TyG index and CI. METHODS: This community population-based cross-sectional study used a cluster-sampling methodology. All participants underwent the education-based Mini-Mental State Examination (MMSE), and those with CI were identified using standard thresholds. The fasting blood triglyceride and glucose levels were measured in the morning, and the TyG index was calculated as ln (½ fasting triglyceride level [mg/dL] × fasting blood glucose level [mg/dL]). Multivariable logistic regression and subgroup analysis were used to assess the relationship between the TyG index and CI. RESULTS: This study included 1484 subjects, of which 93 (6.27%) met the CI criteria. Multivariable logistic regression showed that CI incidence increased by 64% per unit increase in the TyG index (odds ratio [OR] = 1.64, 95% confidence interval [CI]: 1.02-2.63, p = 0.042). CI risk was 2.64-fold higher in the highest TyG index quartile compared to the lowest TyG index quartile (OR = 2.64, 95% CI: 1.19-5.85, p = 0.016). Finally, interaction analysis showed that sex, age, hypertension, and diabetes did not significantly affect the association between the TyG index and CI. CONCLUSION: The present study suggested that an elevated TyG index was associated with a higher CI risk. Subjects with a higher TyG index should manage and treat at an early stage to alleviate the cognitive decline.

Associations among Body Mass Index, Waist-to-Hip Ratio, and Cognitive Impairment Tend to Follow an Opposite Trend and Are Sex Specific: A Population-Based Cross-Sectional Study in a Rural Area of Xi'an, China.

INTRODUCTION: The relationship between obesity and cognitive impairment (CI) is highly heterogeneous in previous studies, which may be due to insufficient consideration of anthropometric indicators and sex. This study compared the cross-sectional relationships among body mass index (BMI), waist-to-hip ratio (WHR), and CI among people aged ≥40 years, and sex-specific relationships were also considered. METHODS: This was a population-based cross-sectional study with a cluster sampling design. CI was defined as a Mini-Mental State Examination score lower than the cutoff value. Multivariate logistic regression was used. BMI and WHR were fitted as both restricted cubic splines and categorical data. Stratified analysis and interaction analysis were performed to explore the sex-specific relationship. RESULTS: A total of 1,792 subjects (40.5% male) were analyzed, and 230 were confirmed to have CI. The relationships among BMI, WHR, and CI were significant (poverall = 0.023, pnonlinear = 0.097; poverall = 0.017, pnonlinear = 0.078, respectively) but exhibited an opposite trend in the total population in the analyses with BMI and WHR as restricted cubic splines. Further categorical analyses showed that subjects with a BMI <23 kg/m2 tended to have a higher risk of CI than those with BMI ≥23 kg/m2 (16.2% vs. 11.8%, p = 0.017; OR = 1.366 [0.969-1.926], p = 0.075), and subjects with a WHR >0.92 had a significantly higher risk of CI than those with a WHR ≤0.92 (11.7% vs. 16.2%, p = 0.011; OR = 1.619 [1.161-2.258], p = 0.005). In addition, the relationship between a low BMI and CI was more significant in males (p = 0.034), while the relationship between a high WHR and CI was more significant in females (p = 0.002). Further studies are needed to confirm the sex differences because of the marginal significance result in the interaction analysis (p = 0.051 for interaction term BMI × sex; p = 0.056 for interaction term WHR × sex). CONCLUSION: The relationships among BMI, WHR, and CI exhibit an opposite trend. A low BMI or high WHR was positively associated with CI, which was more prominent in males for a low BMI and females for a high WHR.

Sleep disturbance is associated with mild cognitive impairment: a community population-based cross-sectional study.

BACKGROUND: Sleep is conducive to the elimination of brain metabolites and the recovery of brain function. However, the relationship between sleep disturbance and Mild Cognitive Impairment is not fully been determined. METHODS: This was a community population-based cross-sectional study. A total of 1,443 participants from a village in the suburbs of Xi'an, China were enrolled in 2017. Sleep quality was evaluated using the Pittsburgh sleep quality index (PSQI), and sleep disturbance was defined as a PSQI score > 5. Mini-Mental State Examination (MMSE) was used to assess cognitive function and Mild Cognitive Impairment(MCI) was defined as the MMSE score less than cutoff values and meets the diagnostic criteria. Univariate and multivariate analyses were used to analyze the relationships between sleep disturbance and MCI. RESULTS: Among 1,443 subjects, 69(4.78%) had MCI, and 830 (57.52%) had sleep disturbance. In bivariate analysis, MCI was associated with sleep disturbance (ρ = 0.094, P<0.001). In the binary logistic regression, MCI was positively associated with the sleep disturbance (OR = 2.027, 95%CI = 1.112-3.698, P = 0.021). In the internal constitution of PSQI, MCI was negatively associated with the habitual sleep efficiency (OR = 0.447, 95%CI = 0.299-0.669, P < 0.001). Compared with waking up before or at 7 am, waking up after 7 am (OR = 0.555, 95%CI = 0.309-0.995, P = 0.048), or 8 am (OR = 0.296, 95%CI = 0.097-0.902, P = 0.032) was probably more likely to have normal cognition. However, people who slept more than 8 h a day might be more likely to suffer from MCI (OR = 5.560, 95%CI = 1.419-21.789, P = 0.014). CONCLUSION: Sleep disturbance is associated with Mild Cognitive Impairment. However, the causal relationship between them is not clear. It needs to be further studied.

Apolipoprotein E ε4 Allele is Associated With Plasma Amyloid Beta and Amyloid Beta Transporter Levels: A Cross-sectional Study in a Rural Area of Xi'an, China.

OBJECTIVE: The effects of the Apolipoprotein E (ApoE) genotype on peripheral amyloid beta (Aß) and Aß transporter levels are still unclear. Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) are the major transporter for Aß, which can prevent plasma Aß from flowing into brain. The aim of this study was to investigate the relationships between the ApoE genotype and plasma Aß, sLRP1, sRAGE levels. DESIGN: Cross-sectional study. SETTING: The committee office of the village. PARTICIPANTS: Residents lived in the village for more than 3 years, aged 40-85 years (n = 1,119, 63.5% women). MEASUREMENTS: Plasma biomarkers include ApoE genotype, Aß, sLRP1, sRAGE, fasting blood-glucose, and blood lipids. General information, medical history, living habits, and cognitive status (cognitive impairment or not) were also collected. RESULTS: After controlling for all possible covariates, multiple linear regression analysis showed that the plasma level of Aß42 was higher and log-transformed sLRP1 was lower in ApoE ε4 carriers than that in noncarriers (ßAß42 = 1.214, 95% confidence interval: 0.105-2.316, pAß42 = 0.031; ßsLRP1 = -0.075, 95% confidence interval: -0.129 to -0.021, psLRP1 = 0.006, respectively). Partial correlation analysis showed that plasma Aß40 was positively correlated with log-transformed sLRP1 and log-transformed sRAGE (rsLRP1 = 0.116, psLRP1 <0.001; rsRAGE = 0.078, psLRP1 = 0.009, respectively). Plasma Aß42 was positively correlated with log-transformed sRAGE (r = 0.072, p = 0.017). CONCLUSION: ApoE ε4 carriers had higher plasma Aß42 levels and lower sLRP1 levels. These data indicated that the ApoE ε4 allele may also contribute to the pathogenesis of Alzheimer's disease through its effects on peripheral Aß42 and sLRP1 levels, but it needs to be further elucidated.

The relationship between blood lipids and plasma amyloid beta is depend on blood pressure: a population-based cross-sectional study.

BACKGROUND: It is believed that deposition of amyloid beta (Aß) in the brain is the central pathological changes of Alzheimer's disease (AD), which triggers a series of pathological processes. However, the relationship between dyslipidemia and AD is uncertain. Considering the peripheral Aß levels are related to brain Aß deposition, we explore the relationships between blood lipids and plasma Aß. METHODS: Participants who lived in the selected village of Xi'an for more than 3 years were enrolled, aged 40-85 years (n = 1282, 37.9% male). Fasting blood lipid, plasma Aß levels, basic information and living habits were measured. Multiple linear regressions were used. RESULTS: In total population, blood lipids were not associated with plasma Aß. After stratified by blood pressure, serum total cholesterol (TC) and low-density lipoprotein (LDL-c) were positively associated with plasma Aß42 levels (ßTC = 0.666, PTC = 0.024; ßLDL-c = 0.743, PLDL-c = 0.011, respectively) in normal blood pressure. LDL-c was negatively associated with plasma Aß40 levels (ß = - 0.986, P = 0.037) in high blood pressure. CONCLUSION: Elevated plasma Aß42 levels are associated with higher TC and LDL-c in normal blood pressure. Elevated plasma Aß40 levels are associated with lower LDL-c in high blood pressure. This indicated that the relationships between blood lipids and plasma Aß were confounded by blood pressure.

The gender- and age- dependent relationships between serum lipids and cognitive impairment: a cross-sectional study in a rural area of Xi'an, China.

BACKGROUND: Serum lipids [total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG)] are risk factors for stroke, but the relationships between serum lipids and cognitive impairment have not been verified completely. In this study, we studied the relationships between serum lipids and cognitive impairment and explored whether gender and age had effects on the relationships. METHODS: In this cross-sectional study, we collected serum lipids and cognitive function information from 1762 participants (aged 40-85). Univariate analysis, multivariate analysis, and both gender- and age-based stratified multivariate analysis were used. RESULTS: In the entire sample set, there was no significant correlation between serum lipid parameters (TC, LDL-C, HDL-C and TG) and cognitive impairment. In both gender- and age-based stratified multivariate analysis, high serum TC was positively associated with cognitive impairment in the elderly (> 55) male participants (OR = 4.404, 95% CI = 1.264-15.344, p = 0.02), and high serum LDL-C was positively correlated with cognitive impairment in the elderly female subjects (OR = 2.496, 95% CI = 1.057-5.896, p = 0.037), while high serum TG was negatively associated with cognitive impairment in the middle-aged (≤ 55) male participants (OR = 0.157, 95% CI = 0.051-0.484, p = 0.001). CONCLUSIONS: The relationships between serum lipids and cognitive impairment are gender- and age- dependent, with high serum TC and LDL-C may be risk factors of cognitive impairment in the elderly male and female subjects respectively, while high serum TG may be protector of cognitive impairment in the middle-aged male participants.

Nonlinear relationship between pulse pressure and risk of cognitive impairment: A 4-year community-based cohort study in Xi'an, China.

OBJECTIVES: It has been known that pulse pressure (PP) is a risk factor for cardiovascular disease and stroke, however, the relationship between PP and cognitive impairment is unclear. METHODS: This was a community-based cohort study. Participates were followed-up for 4 years and new-onset cognitive impairment was diagnosed. Multivariable logistic regression and restricted cubic spline (RCS) were used to investigate the relationship between PP and cognitive impairment. Propensity score matching (PSM) and sensitivity analysis among ApoEε4 non-carriers were performed to confirm the results. RESULTS: 1462 participants were included at baseline and 1173 completed the follow-up. There were 42 (3.5%) new-onset cognitive impairment of whom 31 were diagnosed with MCI and 11 with dementia during the follow-up. Multivariable logistic regression analysis showed that PP was positively associated with cognitive impairment (OR = 2.853, 95% CI 1.079-7.548, p = 0.035), and RCS suggested a non-linear relationship (Pnon-linear = 0.034). The risk of cognitive impairment merely changed when the PP was below about 46.7 mmHg and increased rapidly thereafter. After the covariates were well balanced using PSM (standardized mean differences <0.1 for all covariates), logistic regression analysis revealed the risk of cognitive impairment was still higher for those with high PP (OR = 3.369, 95% CI 1.202-9.441, p = 0.021). Sensitivity analysis showed consistent results with primary analysis. CONCLUSION: PP is associated with cognitive impairment in a non-linear manner among middle-aged and elderly. The risk of cognitive impairment increases rapidly when PP exceeds about 46.7 mmHg, which may be informative for subsequent research of PP control ranges.

Effects of Simvastatin on Plasma Amyloid-ß Transport in Patients with Hyperlipidemia: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Abnormal blood lipids are associated with cognitive impairment and amyloid-ß (Aß) deposition in the brain. However, the effects of statins on Alzheimer's disease (AD) have not been determined. OBJECTIVE: Considering that plasma Aß are related to Aß deposition in the brain, we investigated the effects of simvastatin on plasma Aß transport. METHODS: This was a randomized, double-blind, placebo-controlled trial. One hundred and twenty patients with hyperlipidemia were randomly assigned to receive 40 mg of simvastatin per day or matching placebo for 12 weeks (sixty patients per group). Plasma Aß, sLRP1, sRAGE, and lipid levels were measured at baseline and at the 6-week and 12-week visits. RESULTS: The ITT database ultimately included 108 participants (placebo group: n = 53; simvastatin group: n = 55) and 64 (59.3%) were women, ranging in age from 45 to 75 years (mean 57.2±6.9 years). Multiple linear regression analysis showed that, after 12 weeks of follow-up, compared with the placebo group, ΔAß42 levels (the change of Aß42 levels from baseline at week 12) increased more and ΔsRAGE levels decreased more in the simvastatin group (Aß42: ß= 5.823, p = 0.040; sRAGE: ß= -72.012, p = 0.031), and a significant negative association was found between ΔAß42 and ΔsRAGE levels (ß= -0.115, p = 0.045). In addition, generalized estimation equation analysis showed that triglycerides levels were negatively correlated with Aß40 (ß= -16.79, p = 0.023), Aß42 (ß= -6.10, p = 0.001), and sRAGE (ß= -51.16, p = 0.003). CONCLUSION: Daily oral simvastatin (40 mg/day) in patients with hyperlipidemia for 12 weeks can significantly increase plasma Aß42 levels compared with placebo, which was associated with reduced triglycerides and sRAGE levels, indicating that statins may affect plasma Aß transport.

Resting heart rate is associated with novel plasma atherosclerosis biomarkers.

BACKGROUND: Resting heart rate (RHR) is a strong predictor of adverse cardiovascular outcomes. Both soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor for advanced glycation end products (sRAGE) are novel plasma biomarkers for atherosclerosis. In this study, we examined the potential associations between RHR and plasma sLRP1 and sRAGE levels and whether any associations might be modified by apolipoprotein E (APOE) ε4 carrier status. METHODS: This cross-sectional study included 941 apparently healthy adults aged 40 years or older. Plasma sLRP1 and sRAGE levels were measured by a commercial enzyme-linked immunosorbent assay. APOE gene polymorphisms were analyzed by a polymerase chain reaction and Sanger sequencing. RESULTS: RHR was a significant determinant of log-transformed sLRP1 (ß = 0.004; 95% confidence interval [CI], 0.002-0.007; P = 0.001) and log-transformed sRAGE (ß = 0.005; 95% CI, 0.002-0.007; P <0.001) independently of age, sex, body mass index, blood pressure, blood glucose, blood lipids, lifestyle, and medical history. Additionally, APOE ε4 carrier status was inversely associated with log-transformed plasma sLRP1 level (ß = -0.072; 95% CI, -0.130 to -0.015; P = 0.01) and did not modify the relationship between RHR and plasma sLRP1 level. CONCLUSIONS: An elevated RHR was associated with increased sLRP1 and sRAGE values, which was not modified by APOE genotype. The underlying mechanism of this effect may be relevant to the progression of atherosclerosis.

Pulse Pressure Is Associated with Rapid Cognitive Decline over 4 Years: A Population-Based Cohort Study.

Aiming to investigate the relationship between pulse pressure (PP) and cognitive decline, cognitively normal subjects from a community-based longitudinal cohort were followed-up for 4 years. The Mini-Mental State Examination (MMSE) was used to evaluate global cognitive function, and a ≥2-point decrease in the MMSE score from baseline was defined as cognitive decline. Restricted cubic spline, multivariable linear regression and logistic regression were used to investigate the relationship between PP and cognitive decline. A total of 1173 participants completed the follow-up, and 205 (17.5%) met the criteria for cognitive decline. Restricted cubic splines showed no nonlinear relationship between PP and ΔMMSE (Poverall = 0.037, Pnon-linear = 0.289) or cognitive decline (Poverall = 0.003, Pnon-linear = 0.845). Multivariable linear regression analysis showed that PP was positively related to ΔMMSE (b = 0.021, p = 0.020). Multivariable logistic regression analysis showed that PP was positively associated with cognitive decline (OR = 1.020, p = 0.023). A stratified analysis found an association between PP and cognitive decline in participants who were aged ≤65 years, male, and APOEε4 noncarriers and who had school education ≤6 years or hypertension. A sensitivity analysis after propensity-score matching did not alter our findings. These findings highlight that elevated PP is associated with rapid cognitive decline, particularly in males, middle-aged, low-educated, hypertensive individuals and APOEε4 noncarriers.

The Association of Plasma Amyloid-ß and Cognitive Decline in Cognitively Unimpaired Population.

Purpose: This study investigates the relationship between baseline plasma Aß and cognitive decline during follow-up in cognitively unimpaired population. Materials and Methods: Cognitively unimpaired population was selected from people who lived in the suburbs of Xi'an, China. The levels of plasma Aß1-42 and Aß1-40 were tested using commercial enzyme-linked immunosorbent assay (ELISA). The mini-mental state examination (MMSE) and neuropsychological battery were used to assess cognition. Two years later, MMSE was tested again, and significant cognitive decline was defined as a decrease in MMSE scores ≥5 points. Logistic regression analysis was performed to analyze the relationship between baseline plasma Aß and cognitive change during the two-year follow-up. Results: A total of 1144 participants completed the study, among whom 59 subjects (5.2%) presented significant cognitive decline. The high plasma Aß1-42 level group had more significant cognitive decline (P = 0.023). Multivariable logistic regression analysis showed that significant cognitive decline was associated with the high levels of baseline plasma Aß1-42 (OR = 1.043, 95% CI: 1.005-1.083, P = 0.026). However, significant cognitive decline was not associated with baseline plasma Aß1-40 levels and Aß1-42 /Aß1-40 ratio. Conclusion: Population with high level of baseline plasma Aß1-42 manifested significant cognitive decline over 2 years; however, further investigation on the dynamics of plasma Aß and long-term follow-up are needed.

Peripheral Transport Proteins Were Associated with 4-Year Cognitive Decline in APOE ɛ4 Non-Carriers: A Longitudinal, Population-Based Study.

BACKGROUND: Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) play major roles in peripheral clearance of amyloid-ß (Aß). OBJECTIVE: To determine the relationship between baseline sLRP1/sRAGE and early cognitive decline in a longitudinal study and explore the possible effect of apolipoprotein E (APOE) on their association. METHODS: Cognitively normal subjects were followed-up for 4 years. The baseline plasma levels of sLRP1 and sRAGE were measured using commercial ELISA kits. Global cognition was evaluated by Mini-Mental State Examination (MMSE), and cognitive decline was defined as a ≥2-point decrease of MMSE after 4 years. The association between baseline sLRP1/sRAGE and 4-year cognitive decline were analyzed using logistic regression analysis. Interaction analysis was performed to discover the potential effect of APOE genotype on the relationship. RESULTS: 769 participants were included in the final analysis, with 122 subjects (15.86%) were cognitive decline. Baseline sLRP1/sRAGE levels were not associated with 4-year cognitive decline after multivariable adjustments in the total cohort. However, there was significant interaction effect between sRAGE and APOE genotype on cognitive decline (adjusted odds ratio [OR] = 2.09, 95% confidence interval [CI]: 1.13-3.86, p = 0.019). Lower levels of sRAGE were associated with increased risk of cognitive decline among APOE ɛ4 non-carriers (adjusted OR = 1.60, 95% CI: 1.04-2.48, p = 0.034). CONCLUSION: Individuals with lower levels of sRAGE had an increased risk of 4-year cognitive decline in APOE ɛ4 non-carriers, indicating that the association between sRAGE and cognitive decline might depend on the APOE genotype. However, the specific mechanisms need to be further elucidated.

The Relationship Between Pre-existing Coronary Heart Disease and Cognitive Impairment Is Partly Explained by Reduced Left Ventricular Ejection Fraction in the Subjects Without Clinical Heart Failure: A Cross-Sectional Study.

Background: Coronary heart disease (CHD) is closely associated with cognitive impairment, especially in severe cases of heart failure. However, it is unclear whether cardiac systolic function plays a role in the relationship between pre-existing CHD and cognitive impairment in subjects without clinical heart failure. Methods: In total, 208 subjects from the First Affiliated Hospital of Xi'an Jiaotong University were recruited from June 2014 to January 2015, and were divided into CHD (n = 118) and non-CHD (n = 90) groups according to the inclusion and exclusion criteria. The global cognitive function of all subjects was assessed by the Mini-Mental State Examination (MMSE) and cognitive impairment was defined as the score lower than the cutoff value. Left ventricular ejection fraction (LVEF) was measured using transthoracic echocardiograms. The relationship among pre-existing CHD, LVEF, and cognitive impairment was analyzed by multivariate logistic regression. Results: In total, 34 subjects met the criteria of cognitive impairment. Univariate analysis showed that the cognitive impairment prevalence in the CHD group was significantly higher than that in the non-CHD group (22.0 vs. 8.9%, p = 0.011). Multivariate logistic analysis revealed that CHD was significantly associated with a higher risk of cognitive impairment (odds ratio [OR] = 3.284 [95% CI, 1.032-10.450], p = 0.044) after adjusting for confounds except for LVEF. However, the OR of CHD decreased (OR = 2.127 [95% CI, 0.624-7.254], p = 0.228) when LVEF was further corrected as a continuous variable, and LVEF was negatively associated with the risk of cognitive impairment (OR = 0.928 [95% CI, 0.882-0.976], p = 0.004). Conclusion: Pre-existing CHD is associated with a higher risk of cognitive impairment, and such an association can be considerably explained by reduced LVEF. An impaired cardiac systolic function may play a key role in the relationship between CHD and cognitive impairment among patients with pre-heart failure conditions.

Blood Pressure Level Is Associated With Changes in Plasma Aß1 -40 and Aß1-42 Levels: A Cross-sectional Study Conducted in the Suburbs of Xi'an, China.

Objectives: Amyloid-ß (Aß) deposition in the brain is the hallmark of Alzheimer's disease (AD) pathology. Hypertension is a risk factor for AD, but the effects of hypertension on Aß deposition are not fully determined. Considering peripheral Aß closely relates to Aß deposition in the brain, we investigated the relationships between blood pressure (BP) level and plasma Aß concentrations. Methods: One-thousand and sixty-nine participants (age above 45) from a village in the suburbs of Xi'an, China were enrolled. Questionnaires and validated Chinese versions of the Mini-Mental State Examination (MMSE) were used to collect information about vascular risk factors and assess cognition function. The apolipoprotein E (ApoE) genotype was detected using PCR and sequencing. Plasma Aß levels were measured using ELISA. The associations between BP and plasma Aß levels were analyzed by using multivariate linear regression. Results: Plasma Aß1-40 level was higher in high BP group than that in normal BP group (53.34 ± 8.50 pg/ml vs. 51.98 ± 8.96 pg/ml, P = 0.013), in high SBP group than that in normal SBP group (53.68 ± 8.69 pg/ml vs. 51.88 ± 8.80 pg/ml, P = 0.001) and in high MABP group than that in normal MABP group (54.05 ± 8.78 pg/ml vs. 52.04 ± 8.75 pg/ml, P = 0.001). After controlling for the confounding factors, SBP (b = 0.078, P < 0.001), DBP (b = 0.090, P = 0.008) and MABP (b = 0.104, P < 0.001) correlated with plasma Aß1-40 level positively in ApoE ε4 non-carriers, but not ApoE ε4 carriers. Conclusions: Elevated BP levels were associated with increased plasma Aß1-40 levels in middle-aged and elderly ApoE ε4 non-carriers.

Blood Triglyceride and High-Density Lipoprotein Levels Are Associated with Plasma Amyloid-ß Transport: A Population-Based Cross-Sectional Study.

BACKGROUND: Studies have found that blood lipids are associated with plasma amyloid-ß (Aß) levels, but the underlying mechanism is still unclear. Two Aß transporters, soluble form of low-density lipoprotein receptor related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE), are crucial in peripheral Aß transport. OBJECTIVE: The aim was to investigate the effects of lipids on the relationships between plasma Aß and transporter levels. METHODS: This study included 1,436 adults aged 40 to 88 years old. Blood Aß, sLRP1, sRAGE, and lipid levels were measured. Univariate and multivariate analyses were used to analyze the relationships between lipids and plasma Aß, sLRP1, and sRAGE. RESULTS: After adjusting for all possible covariates, high-density lipoprotein (HDL-c) was positively associated with plasma Aß42 and sRAGE (ß= 6.158, p = 0.049; ß= 121.156, p < 0.001, respectively), while triglyceride (TG) was negatively associated with plasma Aß40, Aß42, and sRAGE (ß= -48.389, p = 0.017; ß= -11.142, p = 0.020; ß= -147.937, p = 0.003, respectively). Additionally, positive correlations were found between plasma Aß and sRAGE in the normal TG (Aß40: ß= 0.034, p = 0.005; Aß42: ß= 0.010, p = 0.001) and HDL-c groups (Aß40: ß= 0.023, p = 0.033; Aß42: ß= 0.008, p = 0.002) but not in the high TG and low HDL-c groups. CONCLUSION: Abnormal levels of TG and HDL-c are associated with decreased Aß and sRAGE levels. Positive correlations between plasma Aß and sRAGE were only found in the normal TG and HDL-c groups but not in the high TG and low HDL-c groups. These results indicated that dyslipidemia contributing to plasma Aß levels might also be involved in peripheral Aß clearance.

The Relationships Between Lipid Accumulation Product Levels and Cognitive Decline Over 4 Years in a Rural Area of Xi'an, China.

Background and Aims: The relationships between blood lipid levels and obesity and cognitive impairment have not been fully determined. Considering that the lipid accumulation product (LAP) is a composite index of blood lipid levels and obesity, we investigated the relationships between LAP levels at baseline and cognitive decline over 4 years. Methods: A total of 983 subjects (≥40 years) from a longitudinal cohort in a village of Xi'an, China, who completed the baseline survey were followed-up for 4 years. All participants underwent face-to-face interviews and cognitive assessments at baseline and at the 4-year follow-up. The Mini-Mental State Examination (MMSE) was used to assess cognitive function, and an MMSE score dropping ≥ 2 points from baseline was defined as cognitive decline. The relationships between LAP and cognitive decline were analyzed by linear regression models. Results: During the 4-year follow-up, 172 patients exhibited cognitive decline (17.5%). Univariate analysis showed that the rate of change in MMSE score was significantly different between the low-LAP group and the high-LAP group (t = -2.26, p = 0.024). Multiple linear regression indicated that a high LAP was positively associated with cognitive decline (ß = 0.564, p = 0.012). Stratified multivariate analysis showed that LAP was positively associated with cognitive decline in the normal blood pressure female subgroup (ß = 1.29, p = 0.002) but not in the high blood pressure group or the male group. Conclusions: High LAP is associated with cognitive decline in females with normal blood pressure but not in those with high blood pressure or males. This indicates that the relationships between blood lipid levels and obesity and cognitive impairment may be affected by blood pressure and sex.

The Apolipoprotein E ε4 Allele-Dependent Relationship Between Serum Lipid Levels and Cognitive Function: A Population-Based Cross-sectional Study.

Objectives: Till now, the effect of serum lipid levels on cognitive function is still controversial. The apolipoprotein E (APOE) ε4 allele is the most critical genetic risk factor for Alzheimer's disease (AD) and cognitive impairment. Additionally, APOE ε4 allele has a major impact on lipid metabolism. The aim of this study was to investigate the APOE genotype-dependent relationship between peripheral serum lipid levels and cognitive impairment. Methods: A total of 1,273 subjects aged 40-86 years participated in this cross-sectional study. Serum lipid levels and the APOE genotype were detected. Mini-Mental State Examination was used to diagnose the cognitive impairment or not. Univariate and multivariate analyses were used to analyze the relationships between APOE genotype, serum lipid levels, and cognition function. Results: After controlling for all possible covariates, a significant interaction between low serum high-density lipoprotein and the APOE ε4 allele on cognitive impairment (Wald's χ2 = 4.269, df = 1, OR = 20.094, p = 0.039) was found in the total participants. In APOE ε4 carriers, low serum high-density lipoprotein was positively associated with cognitive impairment (Wald's χ2 = 8.200, df = 1, OR = 60.335, p = 0.004) and serum high-density lipoprotein levels were positively correlated with Mini-Mental State Examination score (r = 0.217, df = 176, p = 0.004). There was no significant correlation between serum total cholesterol (TC), low-density lipoprotein, triglycerides (TG) levels, and cognitive impairment in either the total participants or APOE ε4 carriers/non-carriers. Conclusions: APOE ε4 carriers, but not non-carriers, with lower serum high-density lipoprotein had a higher prevalence of cognitive impairment and a lower Mini-Mental State Examination score. These results suggest that the APOE ε4 allele may affect the relationship between serum lipid levels and cognitive impairment. However, the specific mechanism needs to be further elucidated.

Non-linear Relationship Between Plasma Amyloid-ß 40 Level and Cognitive Decline in a Cognitively Normal Population.

OBJECTIVES: Recent studies regarding the relationships between plasma amyloid-ß (Aß) levels and cognitive performance had inconsistent results. In this study, we aimed to characterize the relationship between cognitive decline and plasma Aß levels in a large-sample cognitively normal population. METHODS: This population-based, prospective cohort study included 1,240 participants with normal cognition. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and 2 years later. Restricted cubic splines, multivariate logistic regression, and multivariate linear regression models were used to evaluate the type of relationship between cognitive decline during the 2-year follow-up period and plasma Aß levels (Aß40, Aß42, and Aß42 / 40). RESULTS: Participants with moderate Aß40 levels had the highest risk of cognitive decline during a 2-year follow-up relative to individuals with low Aß40 [odds ratio (OR): 0.60, 95% confidence interval (CI): 0.45-0.81, p < 0.001] or high Aß40 (OR: 0.65, 95% CI: 0.49-0.87, p = 0.004) levels. The association between Aß40 and cognitive decline did not depend on sex, education level, or APOE ε4 status. There was an interaction found between age (≤ 65 and > 65 years) and Aß40 (p for interaction = 0.021). In individuals older than 65 years, there was a positive linear relationship between plasma Aß40 and cognitive decline (OR: 1.02, 95% CI: 1.00-1.04, p = 0.027). For participants ≤ 65 years old, the lower Aß40 and higher Aß40 groups had a lower risk of cognitive decline than the medium Aß40 group (OR: 0.69, 95% CI: 0.50-0.94, p = 0.02; OR: 0.63, 95% CI: 0.45-0.86, p = 0.004). None of relationship between plasma Aß42, Aß42 / 40 and cognitive decline was found during a 2-year follow-up. CONCLUSION: The relationship between plasma Aß40 and cognitive decline was not linear, but an inverted-U shape in a cognitively normal population. The underlying mechanism requires further investigation.

Sleep Disturbance is Associated With Higher Plasma Aß Levels in Cognitively Normal Adults-A Population-Based Cross-Sectional Study.

Objective: Growing evidence suggests that sleep disturbance is a risk factor for Alzheimer's disease (AD). Amyloid-ß (Aß) deposition in the brain is a main pathophysiology of AD. Considering that peripheral Aß level is associated with brain Aß deposition, the present study investigated the relationship between sleep disturbance and plasma Aß levels. Methods: This is a population-based cross-sectional study. A total of 1,459 participants from a village in the suburbs of Xi'an, China, were enrolled from January 3, 2017 to March 26, 2017. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and a PSQI score of <5 points was considered as good sleep quality and a PSQI score of >10 points as poor sleep quality. Cognitive function was assessed with the Mini-Mental State Examination (MMSE). Fasting venous blood was taken in the morning, and the plasma Aß levels were measured using ELISA. The relationships between plasma Aß levels and sleep quality were analyzed using multiple linear regression. Results: Among the participants, 231 had poor sleep quality (15.83%). The log-transformed Aß40 level had significant differences among the different sleep groups (F = 3.216, p = 0.040). The log-transformed Aß40 level was higher in the poor sleep quality group than that in the general sleep quality group [87.17 (73.42, 107.34) vs. 89.69 (74.81, 125.79) pg/ml, p = 0.016]. In bivariate analysis, sleep quality was negatively associated with the log-transformed plasma Aß40 level (ß = -0.025, p = 0.011). Conclusion: In the community population, poorer sleep quality is associated with a higher plasma Aß40 level. This indicated that sleep disturbance might also involve in dysfunction of peripheral Aß clearance.

Relationship Between Peripheral Transport Proteins and Plasma Amyloid-ß in Patients with Alzheimer's Disease Were Different from Cognitively Normal Controls: A Propensity Score Matching Analysis.

BACKGROUND: Transport proteins, soluble LRP1 (sLRP1) and soluble RAGE (sRAGE), play a pivotal role in the peripheral clearance of plasma amyloid-ß (Aß). However, their relationship is seldom discussed, especially in Alzheimer's disease (AD). OBJECTIVE: To explore whether their relationship in patients with AD varied from those in cognitively normal (CN) controls. METHODS: We initially recruited 70 patients with AD and 725 CN controls, then applied propensity score matching (PSM) analysis to balance the differences between two groups. Plasma levels of sLRP1, sRAGE, and Aß were measured using commercial ELISA kits and log transformed when skewed distributed. The relationship between sLRP1/sRAGE and plasma Aß were analyzed using Pearson's correlation analysis followed by multiple linear regression separately in the original population and matched participants. RESULTS: After PSM, 70 patients with AD and 140 matched controls were included for further analysis. Log sLRP1 was positively correlated with plasma Aß40 in matched CN controls (r = 0.222, p = 0.008) but not in patients with AD (r = 0.137, p = 0.260). After multivariable adjustment, Log sLRP1 remained significantly associated with plasma Aß40 in the CN group (ß= 7.347, p = 0.014) but not in the AD group (ß= 10.409, p = 0.105). In contrast, Log sLRP1 was not correlated with plasma Aß42 in patients with AD or CN controls, and Log sRAGE was consistently not associated with plasma Aß40 or Aß42 in either group. CONCLUSION: The significant correlation between sLRP1 and plasma Aß40 present in CN controls was not found in patients with AD, suggesting that their relationship was different in AD. However, the specific mechanisms and its influence on cerebral amyloid burden require further validation.