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.

Serum TRPA1 mediates the association between olfactory function and cognitive function.

Background: Olfactory dysfunction was associated with poorer cognition. However, the association between transient receptor potential cation channel subfamily A member 1 (TRPA1) and cognitive function have not been studied. This study aimed to evaluate the mediation effect of TRPA1 on the association between olfactory and cognitive function among Chinese older adults. Methods: We recruited 121 participants with cognitive impairment (CI) and 135 participants with normal cognition (NC) from a memory clinic and the "Shanghai Aging Study." Olfactory identification of each participant was measured by the Sniffin' Sticks Screening Test 12 (SSST-12). Serum TRPA1 were quantified using the Enzyme-Linked Immunosorbent Assay. The mediation effects of TRPA1 on the association between olfactory function and cognitive function were explored using mediation analysis. Results: The CI group had a significantly higher proportion of the high level of serum TRPA1 (58.7%) than the NC group (42.2%) (p = 0.0086). After adjusted for gender, age, and years of education, mediation analysis verified that TRPA1 partially mediated the association between SSST-12 and Mini Mental State Examination (MMSE). It also verified that TRPA1 partially mediated the association between the identification of peppermint and MMSE. Conclusion: Our study emphasizes the mediation role of TRPA1 in the relationship between olfactory and cognitive function among older adults. Further research is necessary to explore the mechanism of TRPA1 on the relationship between olfactory and cognitive decline.

Using a smartphone-based self-management platform to study sex differences in Parkinson's disease: multicenter, cross-sectional pilot study.

BACKGROUND: Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson's disease (PD) is hardly extensively researched. METHODS: A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. RESULTS: Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P < 0.001). For motor symptoms, a higher proportion of patients reporting dyskinesia was observed in the female group. For non-motor symptoms, there is a higher percentage (P < 0.001) as well as severity (P = 0.016) of depression in the female group. More male patients reported hyposmia, lisp, drooling, dysuria, frequent urination, hypersexuality, impotence, daytime sleepiness, and apathy than females (P < 0.05). In contrast, more female patients reported headache, palpation, body pain, anorexia, nausea, urinal incontinence, anxiety, insomnia (P < 0.05) than males. CONCLUSIONS: We provide evidence for sex differences in PD through the data collected from our platform. These results highlighted the importance of gender in clinical decision-making, and also support the feasibility of remote PRO measurement through a smartphone-based self-management platform in patients with PD.

Disease progression in proposed brain-first and body-first Parkinson's disease subtypes.

A new Parkinson's disease (PD) subtyping model has been recently proposed based on the initial location of α-synuclein inclusions, which divides PD patients into the brain-first subtype and the body-first subtype. Premotor RBD has proven to be a predictive marker of the body-first subtype. We found compared to PD patients without possible RBD (PDpRBD-, representing the brain-first subtype), PD patients with possible premotor RBD (PDpRBD+, representing the body-first subtype) had lower Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS UPDRS-III) score (p = 0.022) at baseline but presented a faster progression rate (p = 0.009) in MDS UPDRS-III score longitudinally. The above finding indicates the body-first subtype exhibited a faster disease progression in motor impairments compared to the brain-first subtype and further validates the proposed subtyping model.

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.

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.

The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson's disease in mainland China.

So far, over 20 causative genes of monogenic Parkinson's disease (PD) have been identified. Some causative genes of non-parkinsonian entities may also manifest with parkinsonism mimicking PD. This study aimed to investigate the genetic characteristics of clinically diagnosed PD with early onset age or family history. A total of 832 patients initially diagnosed with PD were enrolled, of which, 636 were classified into the early-onset group and 196 were classified into the familial late-onset group. The genetic testing included the multiplex ligation-dependent probe amplification and next generation sequencing (target sequencing or whole-exome sequencing). The dynamic variants of spinocerebellar ataxia were tested in probands with family history. In the early-onset group, 30.03% of patients (191/636) harbored pathogenic/likely pathogenic (P/LP) variants in known PD-related genes (CHCHD2, DJ-1, GBA (heterozygous), LRRK2, PINK1, PRKN, PLA2G6, SNCA and VPS35). Variants in PRKN were the most prevalent, accounting for 15.72% of the early-onset patients, followed by GBA (10.22%), and PLA2G6 (1.89%). And 2.52% (16/636) had P/LP variants in causative genes of other diseases (ATXN3, ATXN2, GCH1, TH, MAPT, GBA (homozygous)). In the familial late-onset group, 8.67% of patients (17/196) carried P/LP variants in known PD-related genes (GBA (heterozygous), HTRA2, SNCA) and 2.04% (4/196) had P/LP variants in other genes (ATXN2, PSEN1, DCTN1). Heterozygous GBA variants (7.14%) were the most common genetic cause found in familial late-onset patients. Genetic testing is of vital importance in differential diagnosis especially in early-onset and familial PD. Our findings may also provide some clues to the nomenclature of genetic movement disorders.

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.

Plasma GFAP in Parkinson's disease with cognitive impairment and its potential to predict conversion to dementia.

Glial fibrillary acidic protein (GFAP) has been suggested as a biomarker for reactive astrogliosis. We measured the levels of plasma GFAP by Simoa in 60 patients with PD with normal cognition, 63 with mild cognitive impairment (PD-MCI), 24 with dementia (PDD) and 15 healthy controls. A subgroup of patients with PD-MCI (n = 31) was followed up for 4.1 ± 2.3 years. Compared with healthy controls, plasma GFAP levels were elevated in patients with PDD (adjusted P < 0.001) and PD-MCI (adjusted P = 0.013) and were negatively correlated with the Mini Mental State Examination (MMSE) score in PD participants. Plasma GFAP predicted MCI-to-dementia conversion with an AUC of 0.90, higher than NfL, Tau and pTau181. Our results support that plasma GFAP has potential value for distinguishing patients with PDD, and predicting MCI-to-dementia conversion in PD.

Heath management app use in Parkinson's disease and quality of life during the COVID-19 pandemic.

BACKGROUND: Social distancing during the COVID-19 pandemic affected follow-up visits and medication availability for patients with Parkinson's disease (PD). As a promising strategy to deal with these challenges, the implementation of health management smartphone apps was accelerated. However, whether more intense use of such apps could improve the quality of life (QoL) for PD patients during the COVID-19 pandemic was unknown. METHODS: Using a PD management app, this observational study assessed changes in QoL, as determined by PD Questionnaire 8 (PDQ-8), among PD patients before (Jan 20, 2019 to Oct 6, 2019) and after the beginning of the COVID-19 lockdown (Jan 20, 2020 to Oct 6, 2020). According to adherence to use of the app, participants were divided into low adherence, moderate adherence, and high adherence groups. A total of 4979 PD patients registered in the app, and 226 PD patients were enrolled, including 57 patients with low adherence, 112 with moderate adherence and 57 with high adherence. A generalized linear model was used to evaluate the change of PDQ-8 scores across these three different adherence groups. RESULTS: After the COVID-19 lockdown (1-year follow-up), the PDQ-8 scores are reduced by 0.8 (95% CI, 0.3-1.4) in all participants (P = 0.004). After adjustment for age, gender, education, disease duration and levodopa equivalent dose, PDQ-8 scores significantly less reduced in the high adherence group (0.3; 95% CI, 0.6-1.2) compared to the low adherence (1.9; 95% CI, 0.7-3.1) (P = 0.040) and moderate adherence groups (0.6; 95% CI, 0.2-1.3) (P = 0.012). CONCLUSIONS: A health management smartphone-based app might be a way to both measure and improve QoL among PD patients, provided that sufficient adherence is achieved.

The COVID-19 pandemic had an enormous impact on the lives of people living with Parkinson's disease (PD), given social distancing measures, and reduced access to healthcare. As a way to mitigate this, the use of health management apps was accelerated. However, there is a lack of studies on whether the use of such apps could over time affect the quality of life of people living with PD. Here, we analyzed changes in the quality of life of people living with PD using a health management app, before and after social distancing. We found that patients with high adherence to use of the app experienced a lower reduction of their quality of life. Using a health management smartphone app represents a novel approach that might help patients with PD improve their quality of life.

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.

18 F-Florzolotau Positron Emission Tomography Imaging of Tau Pathology in the Living Brains of Patients with Corticobasal Syndrome.

BACKGROUND: Recent development in tau-sensitive tracers has sparkled significant interest in tracking tauopathies using positron emission tomography (PET) biomarkers. However, the ability of 18 F-florzolotau PET imaging to topographically characterize tau pathology in corticobasal syndrome (CBS) remains unclear. Further, the question as to whether disease-level differences exist with other neurodegenerative tauopathies is still unanswered. OBJECTIVE: To analyze the topographical patterns of tau pathology in the living brains of patients with CBS using 18 F-florzolotau PET imaging and to examine whether differences with other tauopathies exist. METHODS: 18 F-florzolotau PET imaging was performed in 20 consecutive patients with CBS, 20 cognitively healthy controls (HCs), 20 patients with Alzheimer's disease (AD), and 16 patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). Cerebrospinal fluid (CSF) levels of ß-amyloid biomarkers were quantified in all patients with CBS. 18 F-florzolotau uptake was quantitatively assessed using standardized uptake value ratios. RESULTS: Of the 20 patients with CBS, 19 (95%) were negative for CSF biomarkers of amyloid pathology; of them, three had negative 18 F-florzolotau PET findings. Compared with HCs, patients with CBS showed increased 18 F-florzolotau signals in both cortical and subcortical regions. In addition, patients with CBS were characterized by higher tracer retentions in subcortical regions compared with those with AD and showed a trend toward higher signals in cortical areas compared with PSP-RS. An asymmetric pattern of 18 F-florzolotau uptake was associated with an asymmetry of motor severity in patients with CBS. CONCLUSIONS: In vivo 18 F-florzolotau PET imaging holds promise for distinguishing CBS in the spectrum of neurodegenerative tauopathies. © 2023 International Parkinson and Movement Disorder Society.

PDQ-8: A Simplified and Effective Tool Measuring Life Quality in Progressive Supranuclear Palsy.

BACKGROUND: The self-reported quality of life (QoL) should be carefully listened to in progressive supranuclear palsy (PSP) from the patient-centered perspective. However, there was still a lack of short QoL measurement tool in atypical parkinsonism. OBJECTIVE: We aimed to test whether the short Parkinson's Disease Questionnaire-8 (PDQ-8) was effective in assessing QoL in PSP, comparing with Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) and Parkinson's Disease Questionnaire-39 (PDQ-39). METHODS: 132 patients with clinical diagnosed PSP, including PSP-Richardson syndrome (RS) subtype (n = 71) and PSP-non-RS subtype (n = 61) were recruited for clinical evaluation including QoL assessment. The detailed QoL profiles and possibility of using PDQ-8 were systemically analyzed. The determinants to the QoL were then calculated by multivariate linear regression analysis. RESULTS: The PSP-QoL total score summary index (SI) was 22.8 (10.1, 41.1), while the PDQ-8 and PDQ-39 total SI score were 28.1 (12.5, 46.9) and 29.5 (15.4, 49.4). Mobility, activities of daily life, cognition and communication were the main affected QoL subdomains (median SI: 40.0, 31.3, 25.0 and 25.0 respectively). PSP-RS subtype showed more severe damage physically (p<0.001) and mentally (p = 0.002) compared to other subtypes. More importantly, the strong relevance of PDQ-8 and recommended PSP QoL tools were confirmed (p<0.001). In addition, disease severity, depression and daytime sleepiness were proved to be critical determinants for QoL in PSP. CONCLUSIONS: PDQ-8 could be an easy, reliable, and valid tool to evaluate QoL in patients with PSP. Besides motor symptoms, more attention should be paid to non-motor impairment such as depression in PSP.

18F-Florzolotau PET imaging captures the distribution patterns and regional vulnerability of tau pathology in progressive supranuclear palsy.

PURPOSE: Human post mortem studies have described the topographical patterns of tau pathology in progressive supranuclear palsy (PSP). Recent advances in tau PET tracers are expected to herald the next era of PSP investigation for early detection of tau pathology in living brains. This study aimed to investigate whether 18F-Florzolotau PET imaging may capture the distribution patterns and regional vulnerability of tau pathology in PSP, and to devise a novel image-based staging system. METHODS: The study cohort consisted of 148 consecutive patients with PSP who had undergone 18F-Florzolotau PET imaging. The PSP rating scale (PSPrs) was used to measure disease severity. Similarities and differences of tau deposition among different clinical phenotypes were examined at the regional and voxel levels. An 18F-Florzolotau pathological staging system was devised according to the scheme originally developed for post mortem data. In light of conditional probabilities for the sequence of events, an 18F-Florzolotau modified staging system by integrating clusters at the regional level was further developed. The ability of 18F-Florzolotau staging systems to reflect disease severity in terms of PSPrs score was assessed by analysis of variance. RESULTS: The distribution patterns of 18F-Florzolotau accumulation in living brains of PSP showed a remarkable similarity to those reported in post mortem studies, with the binding intensity being markedly higher in Richardson's syndrome. Moreover, 18F-Florzolotau PET imaging allowed detecting regional vulnerability and tracking tau accumulation in an earlier fashion compared with post mortem immunostaining. The 18F-Florzolotau staging systems were positively correlated with clinical severity as reflected by PSPrs scores. CONCLUSIONS: 18F-Florzolotau PET imaging can effectively capture the distribution patterns and regional vulnerability of tau pathology in PSP. The 18F-Florzolotau modified staging system holds promise for early tracking of tau deposition in living brains.

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.