Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study.

BACKGROUND: The blood-based biomarkers are approaching the clinical practice of Alzheimer's disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. METHODS: Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted. RESULTS: The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001). CONCLUSIONS: Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.

Stumbling Blocks in the Investigation of the Relationship Between Age-Related Hearing Loss and Cognitive Impairment.

The relationship between age-related hearing loss (ARHL) and cognitive impairment (CI) remains intricate. However, there is no robust evidence from experimental or clinical studies to elucidate their relationship. The key unaddressed questions are (a) whether there is a causal effect of ARHL on CI and (b) whether efficacious treatment of ARHL (such as hearing-aid use) ameliorates CI and dementia-related behavioral symptoms. Because of several methodological and systematic flaws/challenges, rigorous verification has not been conducted. Addressing these stumbling blocks is essential to unraveling the relationship between ARHL and CI, which motivated us to undertake this review. Here, we discuss the methodological problems from the perspectives of potential confounding bias, assessments of CI and ARHL, hearing-aid use, functional-imaging studies, and animal models based on the latest information and our experiences. We also identify potential solutions for each problem from the viewpoints of clinical epidemiology. We believe that "objectivity," specifically the use of more objective behavioral assessments and new computerized technologies, may be the key to improving experimental designs for studying the relationship between ARHL and CI.

Structural, static, and dynamic functional MRI predictors for conversion from mild cognitive impairment to Alzheimer's disease: Inter-cohort validation of Shanghai Memory Study and ADNI.

Mild cognitive impairment (MCI) is a critical prodromal stage of Alzheimer's disease (AD), and the mechanism underlying the conversion is not fully explored. Construction and inter-cohort validation of imaging biomarkers for predicting MCI conversion is of great challenge at present, due to lack of longitudinal cohorts and poor reproducibility of various study-specific imaging indices. We proposed a novel framework for inter-cohort MCI conversion prediction, involving comparison of structural, static, and dynamic functional brain features from structural magnetic resonance imaging (sMRI) and resting-state functional MRI (fMRI) between MCI converters (MCI_C) and non-converters (MCI_NC), and support vector machine for construction of prediction models. A total of 218 MCI patients with 3-year follow-up outcome were selected from two independent cohorts: Shanghai Memory Study cohort for internal cross-validation, and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort for external validation. In comparison with MCI_NC, MCI_C were mainly characterized by atrophy, regional hyperactivity and inter-network hypo-connectivity, and dynamic alterations characterized by regional and connectional instability, involving medial temporal lobe (MTL), posterior parietal cortex (PPC), and occipital cortex. All imaging-based prediction models achieved an area under the curve (AUC) > 0.7 in both cohorts, with the multi-modality MRI models as the best with excellent performances of AUC > 0.85. Notably, the combination of static and dynamic fMRI resulted in overall better performance as relative to static or dynamic fMRI solely, supporting the contribution of dynamic features. This inter-cohort validation study provides a new insight into the mechanisms of MCI conversion involving brain dynamics, and paves a way for clinical use of structural and functional MRI biomarkers in future.

Plasma p-tau217, p-tau181, and NfL as early indicators of dementia risk in a community cohort: The Shanghai Aging Study.

INTRODUCTION: Blood biomarkers showed values for predicting future cognitive impairment. Evidence from the community-based cohort was limited only in high-income countries. METHODS: This study included 1857 dementia-free community residents recruited in 2009-2011 and followed up in waves 2014-2016 and 2019-2023 in the Shanghai Aging Study. We intended to explore the relationships of baseline plasma ALZpath phosphorylated tau 217 (p-tau217), p-tau181, neurofilament light chain (NfL) with follow-up incident dementia, Alzheimer's disease (AD), and amyloidosis. RESULTS: Higher concentrations of plasma p-tau217, p-tau181, and NfL were correlated to higher decline speed of Mini-Mental State Examination score, and higher risk of incident dementia and AD. The p-tau217 demonstrated a significant correlation with longitudinal neocortical amyloid-beta (Aß) deposition (r = 0.57 [0.30, 0.76]) and a high accuracy differentiating Aß+ from Aß- at follow-ups (area under the receiver operating characteristic curve = 0.821 [0.703, 0.940]). DISCUSSION: Plasma p-tau217 may be an early predictive marker of AD and Aß pathology in older community-dwelling individuals.Highlights: Plasma p-tau217, p-tau181, and NfL were positively associated with long-term cognitive decline and risk of incident dementia.Plasma p-tau217 showed a better performance distinguishing Aß+ individuals from Aß- individuals at follow-ups.Plasma NfL may be a suitable predictor of general cognitive decline in older community-dwelling individuals.

Olfactory function, neurofilament light chain, and cognitive trajectory: A 12-year follow-up of the Shanghai Aging Study.

This study aimed to determine whether blood neurofilament light chain (NfL) modifies the association of olfactory dysfunction (OD) with long-term cognitive decline. A total of 1125 non-demented older adults in the Shanghai Aging Study were evaluated for baseline olfaction (12-item Sniffin' Sticks Smell Test) and cognitive trajectory by a 12-year follow-up. Baseline blood NfL was quantified using Single Molecular Array assay, and dichotomized into low and high levels based on the median value of concentration. The Mini-Mental State Examination (MMSE) and Telephone Interview for Cognitive Status-40 were used to assess participants' cognitive function. Cognitive decline was ascertained when dementia was diagnosed or documented in the medical record during follow-up, or the MMSE declining rate (slope) was 1.0 SD larger than the group mean. OD participants presented a steeper trajectory of MMSE score (p interaction = 0.004) and a high risk of cognitive decline (adjusted HR [95% CI], 1.82 [1.11, 2.98]) only in those with high NfL. Participants with combined OD and high NfL showed the highest risk of cognitive decline (adjusted HR, 2.43 [1.20, 4.92]). OD, especially in combination with high blood NfL concentration, may be able to identify individuals who later incur cognitive deterioration.

Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints.

BACKGROUND: Gaining more information about the reciprocal associations between different biomarkers within the ATN (Amyloid/Tau/Neurodegeneration) framework across the Alzheimer's disease (AD) spectrum is clinically relevant. We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography (PET) ATN biomarkers in subjects with cognitive complaints. METHODS: A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging (18F-florbetapir for A, 18F-Florzolotau for T, and 18F-fluorodeoxyglucose [18F-FDG] for N) was enrolled (n = 137). The ß-amyloid (Aß) status (positive versus negative) and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances. RESULTS: Plasma phosphorylated tau 181 (p-tau181) level was found to be associated with PET imaging of ATN biomarkers in the entire cohort. Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aß+ and Aß- subjects. An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aß+ subjects. Additionally, glucose hypometabolism - along with elevated plasma neurofilament light chain level - was related to more severe cognitive impairment in Aß- subjects. CONCLUSION: Plasma p-tau181, as well as 18F-florbetapir and 18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aß status in symptomatic stages of AD. 18F-Florzolotau and 18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment. Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.

Association between occlusal support and cognitive impairment in older Chinese adults: a community-based study.

Introduction: The loss of occlusal support due to tooth loss is associated with systemic diseases. However, there was little about the association between occlusal support and cognitive impairment. The cross-sectional study aimed to investigate their association. Methods: Cognitive function was assessed and diagnosed in 1,225 community-dwelling adults aged 60 years or older in Jing'an District, Shanghai. Participants were diagnosed with mild cognitive impairment (MCI) by Peterson's criteria, or dementia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We determined the number of functional occlusal supporting areas according to Eichner classifications. We used multivariate logistic regression models to analyze the relationship between occlusal support and cognitive impairment and mediation effect models to analyze the mediation effect of age. Results: Six hundred sixty participants were diagnosed with cognitive impairment, averaging 79.92 years old. After adjusting age, sex, education level, cigarette smoking, alcohol drinking, cardiovascular disease, and diabetes, individuals with poor occlusal support had an OR of 3.674 (95%CI 1.141-11.829) for cognitive impairment compared to those with good occlusal support. Age mediated 66.53% of the association between the number of functional occlusal supporting areas and cognitive impairment. Discussion: In this study, cognitive impairment was significantly associated with the number of missing teeth, functional occlusal areas, and Eichner classifications with older community residents. Occlusal support should be a significant concern for people with cognitive impairment.

The heterogeneity of asymmetric tau distribution is associated with an early age at onset and poor prognosis in Alzheimer's disease.

PURPOSE: Left-right asymmetry, an important feature of brain development, has been implicated in neurodegenerative diseases, although it's less discussed in typical Alzheimer's disease (AD). We sought to investigate whether asymmetric tau deposition plays a potential role in AD heterogeneity. METHODS: Two independent cohorts consisting of patients with mild cognitive impairment due to AD and AD dementia with tau PET imaging were enrolled [the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with 18F-Flortaucipir, the Shanghai Memory Study (SMS) cohort with 18F-Florzolotau]. Based on the absolute global tau interhemispheric differences, each cohort was divided into two groups (asymmetric versus symmetric tau distribution). The two groups were cross-sectionally compared in terms of demographic, cognitive characteristics, and pathological burden. The cognitive decline trajectories were analyzed longitudinally. RESULTS: Fourteen (23.3%) and 42 (48.3%) patients in the ADNI and SMS cohorts showed an asymmetric tau distribution, respectively. An asymmetric tau distribution was associated with an earlier age at disease onset (proportion of early-onset AD: ADNI/SMS/combined cohorts, p = 0.093/0.026/0.001) and more severe pathological burden (i.e., global tau burden: ADNI/SMS cohorts, p < 0.001/= 0.007). And patients with an asymmetric tau distribution were characterized by a steeper cognitive decline longitudinally (i.e., the annual decline of Mini-Mental Status Examination score: ADNI/SMS/combined cohorts, p = 0.053 / 0.035 / < 0.001). CONCLUSIONS: Asymmetry in tau deposition, which may be associated with an earlier age at onset, more severe pathological burden, and a steeper cognitive decline, is potentially an important characteristic of AD heterogeneity.

Cognitive impairment as a comorbidity of epilepsy in older adults: Analysis of global and domain-specific cognition.

OBJECTIVE: This study aimed to explore the association between epilepsy and cognitive impairment and to determine the factors associated with cognitive impairment in older people with epilepsy. METHODS: People with epilepsy and controls aged ≥50 years were recruited and their global and domain-specific cognitive functions were evaluated by a comprehensive neuropsychological battery. Clinical characteristics were obtained from medical records. Analysis of covariance was used to examine the difference of cognition between two groups, after adjusting for age, gender, education years, hypertension, diabetes, and heart disease. A multiple linear regression model was used to explore the potential impact factors of cognitive functions among people with epilepsy. RESULTS: This study recruited 90 people with epilepsy and 110 controls. The proportion of cognitive impairment among older adults with epilepsy was 62.2%, which was significantly higher than controls (25.5%, p < .001). People with epilepsy performed worse on global cognition (p < .001), especially in domains of memory (p < .001), executive function (p < .001), language (p < .001), and attention (p = .031). Among older adults with epilepsy, age was negatively correlated with the scores of memory (ß = -.303, p = .029), executive function (ß = -.354, p = .008), and attention (ß = -.558, p < .001). Females performed better on executive function (ß = -.350, p = .002) than males. Education years had a positive correlation with global cognition (ß = .314, p = .004). Number of antiseizure medications was also negatively correlated with scores of spatial construction function (ß = -.272, p = .019). SIGNIFICANCE: Our results indicated that cognitive impairment was a major comorbidity of epilepsy. Number of antiseizure medications is suggested as a potential risk factor of impaired cognition in older people with epilepsy.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Oral microbiome in older adults with mild cognitive impairment.

The association between the oral microbiome and mild cognitive impairment (MCI) remains unclear. This study aimed to investigate such an association among Chinese older adults. Participants without dementia were recruited from the community. A battery of neuropsychological tests was administered to evaluate the cognitive function. The diagnosis of MCI was based on Peterson's criteria. The non-stimulated saliva was collected to extract sequences of the oral microbiome. Forty-seven MCI and 47 cognitively normal participants were included. There was significant difference in alpha diversity and insignificant difference in beta diversity between the two groups of participants. Compared with the cognitively normal group, Gemella haemolysans and Streptococcus gordonii were two significantly decreased species while Veillonella unclassified_Veillonella and Fusobacterium sp._HMT_203 were two significantly increased species in the MCI group. The richness of Gemella haemolysans presented the best discriminate value for MCI with the AUC (Area Under Curve) of 0.707, a cut-off value of 0.008 for relative abundance, the sensitivity of 63.8% and specificity of 70.2%. The dysbiosis of oral microbiome and relative abundance of Gemella haemolysans was significantly associated with MCI. Further studies were needed to develop new treatment strategies targeting the oral microbiome for cognitive impairment.

Apolipoprotein E ε4 Modifies the Effect of Possible Anticholinergic Drugs on Incident Dementia: The Shanghai Aging Study.

OBJECTIVES: To validate the hypothesis that apolipoprotein E (APOE) ε4 modifies the effect of possible anticholinergic drugs (PACDs) on incident dementia among older adults. DESIGN: A population-based prospective study. SETTING AND PARTICIPANTS: Dementia-free older adults in an urban community in Shanghai, China. METHODS: At baseline, PACDs were defined according to the Anticholinergic Cognitive Burden Scale. Standard daily dose (SDD) of PACDs was calculated. A battery of neuropsychological tests was used to assess cognition and the consensus diagnosis was conducted for incident dementia and Alzheimer's disease (AD). Multivariate Cox regression models were used to examine the association between PACD use and the risk of dementia and AD in APOE ε4 carriers and noncarriers. RESULTS: We followed 1406 dementia-free participants for a median of 5.3 years and defined 117 incident dementia cases, among which 89 were AD. Only in APOE ε4 carriers was PACD use associated with incident dementia [hazard ratio (HR) 5.71; 95% CI 2.04-15.94] and AD (HR 5.73; 95% CI 1.77-18.54); SDD was positively associated with incident dementia (HR 2.42; 95% CI 1.32-4.44) and AD (HR 2.16; 95% CI 1.06-4.41). CONCLUSIONS AND IMPLICATIONS: Using PACDs requires judicious consideration for the potential risk of dementia and AD in older adults carrying APOE ε4.

Dose-response relationship between late-life physical activity and incident dementia: A pooled analysis of 10 cohort studies of memory in an international consortium.

INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults. RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week). DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

Education, neighborhood environment, and cognitive decline: Findings from two prospective cohort studies of older adults in China.

INTRODUCTION: The impacts of education on cognitive decline across different neighborhood environments (NEs) have rarely been studied. METHODS: We investigated and compared the associations between educational attainment and cognitive decline using data of 1286 participants from the Taizhou Imaging Study (TIS) and the Shanghai Aging Study (SAS). RESULTS: Compared with low-educated participants, in TIS with disadvantaged NE, high-educated participants manifested a significantly slower decline in global cognition (.062 Z score per year, P < .001), memory (.054 Z score per year, P < .05), and attention (.065 Z score per year, P < .01), whereas in SAS with advanced NE, highly educated individuals exhibited a slower decline only in attention (.028 Z score per year, P < .05). DISCUSSION: We observed the additive effect of educational attainment and NE on cognitive decline in older adults. Education is especially important for maintaining cognitive health in a disadvantaged environment.

Dietary calcium and magnesium intake and risk for incident dementia: The Shanghai Aging Study.

Introduction: Calcium (Ca), magnesium (Mg), or the calcium to magnesium (Ca:Mg) ratio may affect the risk of dementia via complex mechanisms. The aim of this study was to evaluate the association of dietary Ca, Mg, and Ca:Mg ratio with dementia risk at the prospective phase of the Shanghai Aging Study. Methods: We analyzed data from 1565 dementia-free participants living in an urban community who had measurements of dietary Ca and Mg intake derived from a food frequency questionnaire at baseline and incident dementia during follow-up. Results: Over the 5-year follow-up, 162 (10.4%) participants were diagnosed with incident dementia by Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Participants with the lowest tertile of dietary Ca (<339.1 mg/day) and Mg (<202.1 mg/day) had the highest incidence rates of dementia (3.3/100 person-years for Ca, 3.3/100 person-years for Mg) compared to those with higher Ca and Mg intake. In the subgroup with Ca:Mg ratios ≤ 1.69, Mg intake >267.5 mg/day was related to an increased risk for dementia (adjusted hazard ratio: 3.97, 95% confidence interval: 1.29-12.25). Conclusions: Our findings suggest that high dietary intake of Mg is associated with an increased risk of dementia mainly among older adults with low Ca:Mg intake ratios. Proper balance of Ca to Mg in the diet may be critical to the relationship between Mg intake and risk of dementia. Highlights: Participants with the lowest tertile of dietary calcium (Ca) and magnesium (Mg) had the highest incidence rates of dementia.In the subgroup with Ca:Mg ratios ≤1.69, Mg intake >267.5 mg/day was related to an increased risk for dementia.Balance of Ca to Mg in diet may be critical to the relationship between Mg intake and risk of dementia.

Low dietary vitamin E intake is associated with high risk of incident dementia among older adults: The Shanghai Aging Study.

Background: Growing evidence has shown the association between vitamin E intake and the risk of cognitive decline, but the conclusions were inconsistent. This study aimed to verify the hypothesis that vitamin E intake is associated with incident dementia and deterioration of global cognition. Materials and methods: We followed 1,550 non-demented community residents aged ≥60 years for an average of 5.2 years in the Shanghai Aging Study. Baseline vitamin E intake were measured by the Food Frequency Questionnaire. Cognitive function was evaluated by a battery of neuropsychological tests. Consensus diagnosis of incident dementia was made based on the DSM-IV criteria. Results: During the follow-up, 135 cases (8.7%) of incident dementia were identified. The incidence rates of dementia in low, low-medium, medium-high, and high vitamin E intake groups were 2.8, 1.5, 1.6, and 0.7 per 100 person-years, respectively (P < 0.001). Participants with low vitamin E intake had a significantly higher risk of incident dementia than those with higher intake [compared with the highest intake group: hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.20-4.57] after adjusting for confounders. Vitamin E intake was negatively correlated to the rate of annual decline of Mini-Mental State Examination score with the adjustment of confounders (ß = 0.019, p = 0.001). Conclusion: Vitamin E intake is negatively correlated with the risk of dementia in older adults. An appropriate high amount of vitamin E intake from the diet might be helpful to prevent future cognitive decline.

Altered Gut Microbiota and Its Clinical Relevance in Mild Cognitive Impairment and Alzheimer's Disease: Shanghai Aging Study and Shanghai Memory Study.

Altered gut microbiota has been reported in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Previous research has suggested that specific bacterial species might be associated with the decline of cognitive function. However, the evidence was insufficient, and the results were inconsistent. To determine whether there is an alteration of gut microbiota in patients with MCI and AD and to investigate its correlation with clinical characteristics, the fecal samples from 94 cognitively normal controls (NC), 125 participants with MCI, and 83 patients with AD were collected and analyzed by 16S ribosomal RNA sequencing. The overall microbial compositions and specific taxa were compared. The clinical relevance was analyzed. There was no significant overall difference in the alpha and beta diversity among the three groups. Patients with AD or MCI had increased bacterial taxa including Erysipelatoclostridiaceae, Erysipelotrichales, Patescibacteria, Saccharimonadales, and Saccharimonadia, compared with NC group (p < 0.05), which were positively correlated with APOE 4 carrier status and Clinical Dementia Rating (correlation coefficient: 0.11~0.31, p < 0.05), and negatively associated with memory (correlation coefficient: −0.19~−0.16, p < 0.01). Our results supported the hypothesis that intestinal microorganisms change in MCI and AD. The alteration in specific taxa correlated closely with clinical manifestations, indicating the potential role in AD pathogenesis.

Plasma Aß42/Aß40 and p-tau181 Predict Long-Term Clinical Progression in a Cohort with Amnestic Mild Cognitive Impairment.

BACKGROUND: Previous studies reported the value of blood-based biomarkers in predicting Alzheimer disease (AD) progression among individuals with different disease stages. However, evidence regarding the value of these markers in those with amnestic mild cognitive impairment (aMCI) is insufficient. METHODS: A cohort with 251 aMCI individuals were followed for up to 8 years. Baseline blood biomarkers were measured on a single-molecule array platform. Multipoint clinical diagnosis and domain-specific cognitive functions were assessed to investigate the longitudinal relationship between blood biomarkers and clinical AD progression. RESULTS: Individuals with low Aß42/Aß40 and high p-tau181 at baseline demonstrated the highest AD risk (hazard ratio = 4.83, 95% CI 2.37-9.86), and the most dramatic decline across cognitive domains. Aß42/Aß40 and p-tau181, combined with basic characteristics performed the best in predicting AD conversion (AUC = 0.825, 95% CI 0.771-0.878). CONCLUSIONS: Combining Aß42/Aß40 and p-tau181 may be a feasible indicator for AD progression in clinical practice, and a potential composite marker in clinical trials.

Association of occlusal support with type 2 diabetes: A community-based study.

Occlusal support was proved to be associated with type 2 diabetes. Our aim was to investigate the association between the Eichner index and the prevalence of type 2 diabetes. We included 715 participants with oral health examinations in the Shanghai Aging Study. The occlusal support status was determined by the number of functional occlusal support areas and Eichner index classifications. Those with fasting plasma glucose ≥126 mg/dL and/or hemoglobin A1c ≥6.5% and/or current medications for type 2 diabetes with relevant medical history were diagnosed with type 2 diabetes. Multiple logistic regression models were used to analyze the relationship between occlusal support status and type 2 diabetes. The average age of 715 participants was 73.74 ± 6.49 years old. There were 84 diabetics with 1.71 occlusal supporting areas on average. Seven hundred and fifteen participants were divided into 3 groups according to Eichner classifications: Eichner group A with 4 occlusal functional areas, Eichner group B with 1-3 occlusal functional areas or 0 area with anterior occlusal contact, and Eichner group C with no functional occlusal contact. Blood glucose level was significantly lower in participants of Eichner group A compared to those in group B or C. The ordinal logistic regression showed more occlusal supporting areas were significantly associated with less type 2 diabetes cases with an Odds Ratio(OR) of 0.253(95%CI 0.108-0.594) after adjusting covariates. Participants in Eichner group A had a significantly much lower OR of 0.078 for type 2 diabetes (95%CI 0.009-0.694) compared to those in Eichner group C after adjustment. The number of functional occlusal support areas might be inversely related to the blood glucose level and the prevalence of type 2 diabetes.