Joint effect of testosterone and neurofilament light chain on cognitive decline in men: The Shanghai Aging Study.

INTRODUCTION: The association of testosterone and cognitive decline is inconclusive, and its joint effect with neurofilaments light chain (NfL) remains largely unknown. METHODS: A total of 581 non-demented older men in the Shanghai Aging Study were included. Blood total testosterone (TT), free testosterone (FT), and NfL were measured at baseline. The relationships between TT, FT, TT/FT-NfL, and cognitive decline were explored by Cox regression models. RESULTS: During a median follow-up of 6.7 years, there was an inverse association between TT/FT and cognitive decline (TT, trend p = .004, Q1 vs Q4, hazard ratio [HR] = 4.39, 95% confidence interval [CI] = 1.60 to 12.04; FT, trend p = .002, Q1 vs Q4, HR = 5.29, 95% CI = 1.50 to 16.89). Compared to participants with high TT/FT-low NfL, those with low TT/FT-high NfL had significantly higher risks of cognitive decline (TT, HR = 5.10, 95% CI = 1.11 to 23.40; FT, HR = 6.14, 95% CI = 1.34 to 28.06). DISCUSSION: Our findings suggest that the combination of testosterone and neurodegenerative markers may provide reliable predictive insights into future cognitive decline. HIGHLIGHTS: Testosterone is inversely associated with cognitive decline in older men. There is a joint effect of testosterone and NfL on cognitive decline. Sex hormone and neurodegeneration may synergistically contribute to cognitive deterioration.

Characterization of tau propagation pattern and cascading hypometabolism from functional connectivity in Alzheimer's disease.

Tau pathology and its spatial propagation in Alzheimer's disease (AD) play crucial roles in the neurodegenerative cascade leading to dementia. However, the underlying mechanisms linking tau spreading to glucose metabolism remain elusive. To address this, we aimed to examine the association between pathologic tau aggregation, functional connectivity, and cascading glucose metabolism and further explore the underlying interplay mechanisms. In this prospective cohort study, we enrolled 79 participants with 18F-Florzolotau positron emission tomography (PET), 18F-fluorodeoxyglucose PET, resting-state functional, and anatomical magnetic resonance imaging (MRI) images in the hospital-based Shanghai Memory Study. We employed generalized linear regression and correlation analyses to assess the associations between Florzolotau accumulation, functional connectivity, and glucose metabolism in whole-brain and network-specific manners. Causal mediation analysis was used to evaluate whether functional connectivity mediates the association between pathologic tau and cascading glucose metabolism. We examined 22 normal controls and 57 patients with AD. In the AD group, functional connectivity was associated with Florzolotau covariance (ß = .837, r = 0.472, p < .001) and glucose covariance (ß = 1.01, r = 0.499, p < .001). Brain regions with higher tau accumulation tend to be connected to other regions with high tau accumulation through functional connectivity or metabolic connectivity. Mediation analyses further suggest that functional connectivity partially modulates the influence of tau accumulation on downstream glucose metabolism (mediation proportion: 49.9%). Pathologic tau may affect functionally connected neurons directly, triggering downstream glucose metabolism changes. This study sheds light on the intricate relationship between tau pathology, functional connectivity, and downstream glucose metabolism, providing critical insights into AD pathophysiology and potential therapeutic targets.

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.

Incremental value of amyloid PET in a tertiary memory clinic setting in China.

INTRODUCTION: The objective of this study is to investigate the incremental value of amyloid positron emission tomography (Aß-PET) in a tertiary memory clinic setting in China. METHODS: A total of 1073 patients were offered Aß-PET using 18F-florbetapir. The neurologists determined a suspected etiology (Alzheimer's disease [AD] or non-AD) with a percentage estimate of their confidence and medication prescription both before and after receiving the Aß-PET results. RESULTS: After disclosure of the Aß-PET results, etiological diagnoses changed in 19.3% of patients, and diagnostic confidence increased from 69.3% to 85.6%. Amyloid PET results led to a change of treatment plan in 36.5% of patients. Compared to the late-onset group, the early-onset group had a more frequent change in diagnoses and a higher increase in diagnostic confidence. DISCUSSION: Aß-PET has significant impacts on the changes of diagnoses and management in Chinese population. Early-onset cases are more likely to benefit from Aß-PET than late-onset cases. HIGHLIGHTS: Amyloid PET contributes to diagnostic changes and its confidence in Chinese patients. Amyloid PET leads to a change of treatment plans in Chinese patients. Early-onset cases are more likely to benefit from amyloid PET than late-onset cases.

Cerebral pulsatility in relation with various imaging markers of cerebral small vessel disease: a longitudinal community-based study.

Background: Cerebral pulsatility is thought to reflect arterial stiffness and downstream microvascular resistance. Although previous studies indicated cerebral pulsatility might closely relate to development of cerebral small vessel disease (SVD), yet evidence remain controversial and longitudinal data are rare. Objective: We aimed to explore relationships of cerebral pulsatility with severity and progression of various SVD imaging markers among the community-dwelling elderly. Design: A longitudinal cohort study. Methods: As part of the prospective community-based Shanghai Aging Study cohort, dementia- and stroke-free elderly were recruited for baseline assessment of cerebral pulsatility and SVD severity during 2010-2011 and traced for SVD progression during 2016-2017. Cerebral pulsatility was quantified for both anterior and posterior circulation with transcranial Doppler ultrasound. SVD imaging markers were measured with brain magnetic resonance imaging (MRI) including white matter hyperintensities (WMHs), enlarged perivascular spaces (ePVS), lacunes, and microbleeds. The cross-sectional and longitudinal relationships between cerebral pulsatility and SVD were analyzed by univariable and multivariable regression models. Results: Totally, 188 eligible subjects were included at baseline and out of them, 100 (53.19%) returned for a 7-year follow-up. At baseline, increased pulsatility of posterior circulation was independently associated with more periventricular WMH (PWMH) and ePVS in basal ganglia (BG-ePVS) but not with other SVD markers. Longitudinally, higher posterior pulsatility predicted greater PWMH progression in participants with hypertension (ß = 2.694, standard error [SE] = 1.112, p = 0.020), whereas pulsatility of anterior circulation was shown to prevent BG-ePVS progression among followed-up elderly (ß = -6.737, SE = 2.685, p = 0.012). However, no significant relationship was found between cerebral pulsatility and burden of lacunes or cerebral microbleeds. Conclusion: Higher pulsatility of posterior circulation could worsen PWMH progression, especially for participants with hypertension. But for development of ePVS, increased cerebral pulsatility could play a compensatory role among several healthy elderly. The distinct relationships between cerebral pulsatility and various SVD markers emphasized the importance of individualized SVD management.

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.

Interventions for Persons with Young-Onset Dementia and Their Families: A Scoping Review.

Background: Dementia occurring before age 65 is known as young-onset dementia (YOD), with Alzheimer's disease being the most common type. YOD poses unique challenges for persons and families, impacting their working-age years and family responsibilities. Person-centered interventions and services are essential to improve their quality of life and social engagement. Objective: This study aims to synthesize non-pharmacological interventions for persons with YOD and their families to inform future targeted interventions. Methods: We conducted a systematic literature search across four databases: PubMed, PsycINFO, Scopus, and CINAHL. The included articles were carefully screened, categorized, and synthesized by following Arksey and O'Malley's five stages framework. Results: We included 20 studies reported in 24 papers, with 11 studies (14 papers) on persons with YOD and nine studies (10 papers) on families. Quantitative intervention results vary, but qualitative interviews show positive feedback. Stakeholders provided positive evaluations, stating these interventions provided a sense of normalcy, facilitated communication among families, enhanced the independence of persons with YOD, and improved the families' caregiving self-efficacy, thereby reducing care burden and psychological distress. The heterogeneity among the studies posed integration challenges. Conclusions: Interventions for YOD can improve the quality of life for both persons with YOD and their families. More extensive intervention studies are urgently needed, especially in developing countries, with a focus on family-centered and life course perspectives. In future intervention research design, a more extensive incorporation of stakeholder involvement is essential for successful implementation. Moreover, the integration of new technologies shows promise as a potential avenue for intervention advancement.

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.

Early Detection of Dementia using Risk Classification in MCI: Outcomes of Shanghai Mild Cognitive Impairment Cohort Study.

INTRODUCTION: The purpose of this study is to identify the risk factors and risk classification associated with the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia to facilitate early intervention and the design of clinical trials for AD. METHODS: The study comprised a prospective cohort study of 400 subjects with MCI who had annual follow-ups for 3 years. RESULTS: During an average follow-up period of 3.5 years, 109 subjects were diagnosed with all cause of dementia, of whom 104 subjects converted to Alzheimer's dementia and 5 subjects converted to other types of dementia. The cumulative conversion rate was 5.5% (95% CI: 3.4, 8.6), 16.3% (95% CI: 12.9, 21.1), and 31.0% (95% CI: 25.4, 36.5) in each of the first 3 follow-up years, respectively. The factors associated with a greater risk of conversion from MCI to AD included smoking status, ApoE4 carrier status, right hippocampal volume (rt. HV), left temporal lobe volume, and scores on the Revised Chinese version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-C). The risk classification of the ADAS-Cog-C or Preclinical Alzheimer Cognitive Composite (PACC) score combined with the rt. HV showed a conversion difference among the groups at every annual follow-up. CONCLUSION: A simple risk classification using the rt. HV and neuropsychological test scores, including those from the ADAS-Cog-C and PACC, could be a practicable and efficient approach to indentify individuals at risk of all-cause dementia.

Genetic and Neuroimaging Analysis of SIGMAR1 for Frontotemporal Dementia.

BACKGROUND: Recently, Sigma nonopioid intracellular receptor 1 (SIGMAR1) variants have been shown harboring C9orf72 pathogenic repeat expansions in some frontotemporal dementia (FTD) cases. However, no SIGMAR1 genotype analysis has been reported in a cohort absent of C9orf72 pathogenic repeat expansions to date. OBJECTIVE: The present study investigated the contribution of SIGMAR1 independent of C9orf72 gene status to FTD spectrum syndromes. METHODS: We directly sequencing the entire coding region and a minimum of 50 bp from each of the flanking introns of SIGMAR1 gene in 82 sporadic FTD patients (female: male = 42 : 40) and 417 controls. For the patient carrying SIGMAR1 variant, a follow-up 3T MR imaging was performed in the study. RESULTS: Gene sequencing of SIGMAR1 revealed a rare 3'UTR nucleotide variation rs192856872 in a male patient with semantic dementia independent of C9orf72 gene status. The MR imaging showed asymmetrical atrophy in the anterior temporal lobes and the degeneration extends caudally into the posterior temporal lobes as the disease progresses. ESEFinder analysis showed new SRSF1 and SRSF1-IgM-BRCA1 binding sites with significant scores, which is predicted to affect normal splicing. CONCLUSION: We found a novel SIGMAR1 variant independent of C9orf72 gene status associated with semantic dementia phenotype.

Improved interpretation of 18F-florzolotau PET in progressive supranuclear palsy using a normalization-free deep-learning classifier.

While 18F-florzolotau tau PET is an emerging biomarker for progressive supranuclear palsy (PSP), its interpretation has been hindered by a lack of consensus on visual reading and potential biases in conventional semi-quantitative analysis. As clinical manifestations and regions of elevated 18F-florzolotau binding are highly overlapping in PSP and the Parkinsonian type of multiple system atrophy (MSA-P), developing a reliable discriminative classifier for 18F-florzolotau PET is urgently needed. Herein, we developed a normalization-free deep-learning (NFDL) model for 18F-florzolotau PET, which achieved significantly higher accuracy for both PSP and MSA-P compared to semi-quantitative classifiers. Regions driving the NFDL classifier's decision were consistent with disease-specific topographies. NFDL-guided radiomic features correlated with clinical severity of PSP. This suggests that the NFDL model has the potential for early and accurate differentiation of atypical parkinsonism and that it can be applied in various scenarios due to not requiring subjective interpretation, MR-dependent, and reference-based preprocessing.

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.

Pharmacological treatment of neuropsychiatric symptoms of dementia: a network meta-analysis.

BACKGROUND: Pharmacological treatments are very common to be used for alleviating neuropsychiatric symptoms (NPS) in dementia. However, decision on drug selection is still a matter of controversy. AIMS: To summarise the comparative efficacy and acceptability of currently available monotherapy drug regimens for reducing NPS in dementia. METHOD: We searched PubMed, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials between inception and 26 December 2022 without language restrictions; and reference lists scanned from selected studies and systematic reviews. Double-blind randomised controlled trials were identified from electronic databases for reporting NPS outcomes in people with dementia. Primary outcomes were efficacy and acceptability. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). RESULTS: We included 59 trials (15,781 participants; mean age, 76.6 years) and 15 different drugs in quantitative syntheses. Risperidone (standardised mean difference [SMD] -0.20, 95% credible interval [CrI] -0.40 to -0.10) and galantamine (-0.20, -0.39 to -0.02) were more effective than placebo in short-term treatment (median duration: 12 weeks). Galantamine (odds ratio [OR] 1.95, 95% CrI 1.38-2.94) and rivastigmine (1.87, 1.24-2.99) were associated with more dropouts than placebo, and some active drugs. Most of the results were rated as low or very low according to CINeMA. CONCLUSIONS: Despite the scarcity of high-quality evidence, risperidone is probably the best pharmacological option to consider for alleviating NPS in people with dementia in short-term treatment when considering the risk-benefit profile of drugs.

Metabolic Asymmetry Relates to Clinical Characteristics and Brain Network Abnormalities in Alzheimer's Disease.

BACKGROUND: Metabolic asymmetry has been observed in Alzheimer's disease (AD), but different studies have inconsistent viewpoints. OBJECTIVE: To analyze the asymmetry of cerebral glucose metabolism in AD and investigate its clinical significance and potential metabolic network abnormalities. METHODS: Standardized uptake value ratios (SUVRs) were obtained from 18F-FDG positron emission tomography (PET) images of all participants, and the asymmetry indices (AIs) were calculated according to the SUVRs. AD group was divided into left/right-dominant or bilateral symmetric hypometabolism (AD-L/AD-R or AD-BI) when more than half of the AIs of the 20 regions of interest (ROIs) were < -2SD, >2SD, or between±1SD. Differences in clinical features among the three AD groups were compared, and the abnormal network characteristics underlying metabolic asymmetry were explored. RESULTS: In AD group, the proportions of AD-L, AD-R, and AD-BI were 28.4%, 17.9%, and 18.5%, respectively. AD-L/AD-R groups had younger age of onset and faster rate of cognitive decline than AD-BI group (p < 0.05). The absolute values of AIs in half of the 20 ROIs became higher at follow-up than at baseline (p < 0.05). Compared with those in AD-BI group, metabolic connection strength of network, global efficiency, cluster coefficient, degree centrality and local efficiency were lower, but shortest path length was longer in AD-L and AD-R groups (p < 0.05). CONCLUSION: Asymmetric and symmetric hypometabolism may represent different clinical subtypes of AD, which may provide a clue for future studies on the heterogeneity of AD and help to optimize the design of clinical trials.

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.

Feasibility of 18F-florzolotau quantification in patients with Alzheimer's disease based on an MRI-free tau PET template.

OBJECTIVES: Quantification of tau accumulation using positron emission tomography (PET) is critical for the diagnosis of Alzheimer's disease (AD). This study aimed to evaluate the feasibility of 18F-florzolotau quantification in patients with AD using a magnetic resonance imaging (MRI)-free tau PET template, since individual high-resolution MRI is costly and not always available in practice. METHODS: 18F-florzolotau PET and MRI scans were obtained in a discovery cohort including (1) patients within the AD continuum (n = 87), (2) cognitively impaired patients with non-AD (n = 32), and (3) cognitively unimpaired subjects (n = 26). The validation cohort comprised 24 patients with AD. Following MRI-dependent spatial normalization (standard approach) in randomly selected subjects (n = 40) to cover the entire spectrum of cognitive function, selected PET images were averaged to create the 18F-florzolotau-specific template. Standardized uptake value ratios (SUVRs) were calculated in five predefined regions of interest (ROIs). MRI-free and MRI-dependent methods were compared in terms of continuous and dichotomous agreement, diagnostic performances, and associations with specific cognitive domains. RESULTS: MRI-free SUVRs had a high continuous and dichotomous agreement with MRI-dependent measures for all ROIs (intraclass correlation coefficient ≥ 0.980; agreement ≥ 94.5%). Similar findings were observed for AD-related effect sizes, diagnostic performances with respect to categorization across the cognitive spectrum, and associations with cognitive domains. The robustness of the MRI-free approach was confirmed in the validation cohort. CONCLUSIONS: The use of an 18F-florzolotau-specific template is a valid alternative to MRI-dependent spatial normalization, improving the clinical generalizability of this second-generation tau tracer. KEY POINTS: • Regional 18F-florzolotau SUVRs reflecting tau accumulation in the living brains are reliable biomarkers for the diagnosis, differential diagnosis, and assessment of disease severity in patients with AD. • The 18F-florzolotau-specific template is a valid alternative to MRI-dependent spatial normalization, improving the clinical generalizability of this second-generation tau tracer.