Association of intrinsic capacity and medication non-adherence among older adults with non-communicable diseases in Taiwan.

OBJECTIVES: Medication non-adherence among older adults with non-communicable diseases (NCDs) remains prevalent worldwide, which causes hospitalization and mortality. Our study aimed to examine the association of medication non-adherence with level of overall intrinsic capacity (IC), pattern of IC, and specific IC component among older adults with NCDs. METHODS: A cross-sectional questionnaire-based survey of 1268 older adults aged 60 years and above was conducted in 2022 in southern Taiwan. Among them, 894 suffered from 1 more NCD were included in this study. The Integrated Care for Older People Screening Tool for Taiwanese and the Adherence to Refills and Medication Scale were used to assess IC and medication non-adherence, respectively. Latent class analysis (LCA) was used to identify patterns of IC impairment, and binary logistic regression was used to assess the association between medication non-adherence and IC. RESULTS: Older adults in the moderate (score: 1-2) or low (score≧3) overall IC groups were more likely to experience medication non-adherence (moderate: adjusted odds ratio (aOR) 1.57 [95% CI: 1.05-2.36]; low: 2.26 [1.40-3.67]). The "physical and nutritional impairments accompanied by depressive symptoms" group was associated with statistically higher odds of medication non-adherence (aOR 1.66 [1.01-2.73]). Older adults with cognitive impairment, hearing loss, or depressive symptoms showed greater likelihood of medication non-adherence (cognitive impairment: aOR 1.53 [1.03-2.27]; hearing loss: aOR 1.57 [1.03-2.37]; depressive symptoms: aOR 1.81 [1.17-2.80]). CONCLUSIONS: Intervention for improving medication non-adherence among older adults with NCDs should consider IC.

Assessing intrinsic capacity in Taiwan: Initial psychometric properties of the Integrated Care for Older People Screening Tool for Taiwanese (ICOPES-TW).

BACKGROUND: The World Health Organization (WHO) proposed the concept of intrinsic capacity (comprising composite physical and mental capacity) which aligns with their concepts of healthy aging and functional ability. Consequently, the WHO promotes the Integrated Care for Older People (ICOPE) framework as guidance for geriatric care. Consequently, each government should have a screening tool corresponding to ICOPE framework to promote geriatric care. The present study examined the initial psychometric properties of the Taiwan version of ICOPE (i.e., ICOPES-TW). METHODS: Older people (n = 1235; mean age = 72.63 years; 634 females [51.3%]) were approached by well-trained interviewers for participation. A number of measures were administered including the ICOPES-TW, WHOQOL-AGE (assessing quality of life [QoL]), Clinical Frailty Scale (assessing frailty), Barthel Index (assessing basic activity of daily living [BADL]), and Lawton Instrumental Activities of Daily Living Scale (assessing instrumental activity of daily living [IADL]). RESULTS: The ICOPES-TW had a two-factor structure (body functionality [eigenvalue = 1.932] and life adaptation [eigenvalue = 1.170]) as indicated by the results of exploratory factor analysis. Internal consistency of the ICOPES-TW was low (Cronbach's α = 0.55 [entire ICOPES-TW], 0.45 (body functionality factor), and 0.52 (life adaptation factor). ICOPES-TW scores were significantly (i) positively correlated with age (r = 0.321), IADL (r = 0.313), and frailty (r = 0.601), and (ii) negatively correlated with QoL (r=-0.447), and BADL (r=-0.447), with all p-values < 0.001. CONCLUSION: The ICOPES-TW could be a useful screening tool for healthcare providers to quickly evaluate intrinsic capacity for Taiwanese older people given that it has moderate to strong associations with age, BADL, IADL, QoL, and frailty.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

Improved support vector machine classification for imbalanced medical datasets by novel hybrid sampling combining modified mega-trend-diffusion and bagging extreme learning machine model.

To handle imbalanced datasets in machine learning or deep learning models, some studies suggest sampling techniques to generate virtual examples of minority classes to improve the models' prediction accuracy. However, for kernel-based support vector machines (SVM), some sampling methods suggest generating synthetic examples in an original data space rather than in a high-dimensional feature space. This may be ineffective in improving SVM classification for imbalanced datasets. To address this problem, we propose a novel hybrid sampling technique termed modified mega-trend-diffusion-extreme learning machine (MMTD-ELM) to effectively move the SVM decision boundary toward a region of the majority class. By this movement, the prediction of SVM for minority class examples can be improved. The proposed method combines α-cut fuzzy number method for screening representative examples of majority class and MMTD method for creating new examples of the minority class. Furthermore, we construct a bagging ELM model to monitor the similarity between new examples and original data. In this paper, four datasets are used to test the efficiency of the proposed MMTD-ELM method in imbalanced data prediction. Additionally, we deployed two SVM models to compare prediction performance of the proposed MMTD-ELM method with three state-of-the-art sampling techniques in terms of geometric mean (G-mean), F-measure (F1), index of balanced accuracy (IBA) and area under curve (AUC) metrics. Furthermore, paired t-test is used to elucidate whether the suggested method has statistically significant differences from the other sampling techniques in terms of the four evaluation metrics. The experimental results demonstrated that the proposed method achieves the best average values in terms of G-mean, F1, IBA and AUC. Overall, the suggested MMTD-ELM method outperforms these sampling methods for imbalanced datasets.

Blood pressure levels within normotensive range are independently associated with increased risk of arterial stiffness in adults without hypertension or prehypertension.

BACKGROUND AND AIMS: High blood pressure (BP) indices, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP) predict cardiovascular diseases and mortality. However, the association of these BP indices with arterial stiffness (AS) in the normotensive population (BP < 120/80 mmHg) remains unclear. METHODS AND RESULTS: Study participants who underwent health checkups at a tertiary referred center were recruited between November 2018 to December 2019. 2129 participants were enrolled after excluding those aged <18 years old, with elevated BP, history of hypertension, cardiovascular disease, and stroke, or with incomplete data. The brachial-ankle pulse wave velocity (baPWV) values were examined for evaluation of AS. Participants with higher blood pressure indices had significantly higher baPWV. Multiple linear regression revealed that all BP indices were positively associated with baPWV. According to the binary logistic regression analysis, participants in the higher SBP and MAP quartiles were significantly related to AS. The odds ratio (OR) for SBP Q2, Q3 and Q4 vs. Q1 were 6.06, 10.06 and 17.78 whereas the OR for MAP Q2, Q3 and Q4 vs. Q1 were: 5.07, 5.28 and 10.34. For DBP and PP, only participants belonging to the highest quartile were associated with AS(OR for DBP Q4 vs. Q1: 2.51; PP Q4 vs Q1: 1.94). CONCLUSIONS: BP indices were linearly related to the baPWV. Normotensive participants with higher quartiles of SBP, DBP, MAP, and PP, remained associated with increased AS. The SBP and MAP levels exhibited a more prominent relationship with AS.

Determination of o-phthalaldehyde for dose verification of the clinical disinfectant by fluorescent sequential injection analysis.

A new automated, generic analytical approach for determining the clinical disinfectant o-phthalaldehyde (OPA) is reported in this study. The proposed sequential injection analysis (SIA) is based on the online reaction of the OPA with glycine/N-acetylcysteine (NAC) in a neutral medium (pH = 7.0) to form a highly fluorescent isoindole derivative. All critical flow and reaction variables were investigated, while validation was carried out in the linearity detection range (0.0075-0.02%). As a result, excellent linearity (R2 > 0.99) and precision (1.5-2.4% for repeatability and 0.7-2.2% for reproducibility) were achieved for the reference OPA solutions. Furthermore, reasonable concentration verification of OPA disinfection (0.2-0.6%) in healthcare institutes can be achieved using the developed fluorescent SIA due to its good sensitivity (0.111 V/%) and precision (1.0-2.3% for intermediate precision) around the minimum effective concentration (MEC) of 0.3% for Cidex-OPA disinfectant.

Association between sleep health and intrinsic capacity among older adults in Taiwan.

Although the association between poor sleep quality and frailty has been previously reported, the relationship between sleep health and intrinsic capacity (IC) remains largely unknown. We aimed to examine the association between sleep health and IC among older adults. This was a cross-sectional study, and 1268 eligible participants completed a questionnaire collecting information on demographic, socioeconomic, lifestyle, sleep health, and IC. Sleep health was measured by the RU-SATED V2.0 scale. High, moderate, and low levels of IC were defined using the Integrated Care for Older People Screening Tool for Taiwanese. The ordinal logistic regression model estimated the odds ratio and corresponding 95% confidence interval. Low IC was significantly associated with age of 80 years or above, female, currently unmarried, uneducated, currently not working, financially dependent, and having emotional disorders. A one-point increase in sleep health was significantly associated with a 9% reduction in the odds of poor IC. An increase in daytime alertness was related to the greatest reduction in poor IC (aOR, 0.64; 95% CI, 0.52-0.79). In addition, the subitems sleep regularity (aOR, 0.77; 95% CI, 0.60-0.99), sleep timing (aOR, 0.80; 95% CI, 0.65-0.99), and sleep duration (aOR, 0.77; 95% CI, 0.61-0.96) were associated with a reduced OR of poor IC but with marginal statistical significance. Our findings showed that sleep health across multiple dimensions is related to IC, particularly daytime alertness in older adults. We suggest developing interventions to improve sleep health and prevent IC decline, which is crucial in causing poor health outcomes.

Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status.

Introduction: Despite the association of vitamin D deficiency with incident dementia, the role of supplementation is unclear. We prospectively explored associations between vitamin D supplementation and incident dementia in 12,388 dementia-free persons from the National Alzheimer's Coordinating Center. Methods: Baseline exposure to vitamin D was considered D+; no exposure prior to dementia onset was considered D-. Kaplan-Meier curves compared dementia-free survival between groups. Cox models assessed dementia incidence rates across groups, adjusted for age, sex, education, race, cognitive diagnosis, depression, and apolipoprotein E (APOE) ε4. Sensitivity analyses examined incidence rates for each vitamin D formulation. Potential interactions between exposure and model covariates were explored. Results: Across all formulations, vitamin D exposure was associated with significantly longer dementia-free survival and lower dementia incidence rate than no exposure (hazard ratio = 0.60, 95% confidence interval: 0.55-0.65). The effect of vitamin D on incidence rate differed significantly across the strata of sex, cognitive status, and APOE ε4 status. Discussion: Vitamin D may be a potential agent for dementia prevention. Highlights: In a prospective cohort study, we assessed effects of Vitamin D on dementia incidence in 12,388 participants from the National Alzheimer's Coordinating Center dataset.Vitamin D exposure was associated with 40% lower dementia incidence versus no exposure.Vitamin D effects were significantly greater in females versus males and in normal cognition versus mild cognitive impairment.Vitamin D effects were significantly greater in apolipoprotein E ε4 non-carriers versus carriers.Vitamin D has potential for dementia prevention, especially in the high-risk strata.

Thousands of conductance levels in memristors integrated on CMOS.

Neural networks based on memristive devices1-3 have the ability to improve throughput and energy efficiency for machine learning4,5 and artificial intelligence6, especially in edge applications7-21. Because training a neural network model from scratch is costly in terms of hardware resources, time and energy, it is impractical to do it individually on billions of memristive neural networks distributed at the edge. A practical approach would be to download the synaptic weights obtained from the cloud training and program them directly into memristors for the commercialization of edge applications. Some post-tuning in memristor conductance could be done afterwards or during applications to adapt to specific situations. Therefore, in neural network applications, memristors require high-precision programmability to guarantee uniform and accurate performance across a large number of memristive networks22-28. This requires many distinguishable conductance levels on each memristive device, not only laboratory-made devices but also devices fabricated in factories. Analog memristors with many conductance states also benefit other applications, such as neural network training, scientific computing and even 'mortal computing'25,29,30. Here we report 2,048 conductance levels achieved with memristors in fully integrated chips with 256 × 256 memristor arrays monolithically integrated on complementary metal-oxide-semiconductor (CMOS) circuits in a commercial foundry. We have identified the underlying physics that previously limited the number of conductance levels that could be achieved in memristors and developed electrical operation protocols to avoid such limitations. These results provide insights into the fundamental understanding of the microscopic picture of memristive switching as well as approaches to enable high-precision memristors for various applications. Fig. 1 HIGH-PRECISION MEMRISTOR FOR NEUROMORPHIC COMPUTING.: a, Proposed scheme of the large-scale application of memristive neural networks for edge computing. Neural network training is performed in the cloud. The obtained weights are downloaded and accurately programmed into a massive number of memristor arrays distributed at the edge, which imposes high-precision requirements on memristive devices. b, An eight-inch wafer with memristors fabricated by a commercial semiconductor manufacturer. c, High-resolution transmission electron microscopy image of the cross-section view of a memristor. Pt and Ta serve as the bottom electrode (BE) and top electrode (TE), respectively. Scale bars, 1 µm and 100 nm (inset). d, Magnification of the memristor material stack. Scale bar, 5 nm. e, As-programmed (blue) and after-denoising (red) currents of a memristor are read by a constant voltage (0.2 V). The denoising process eliminated the large-amplitude RTN observed in the as-programmed state (see Methods). f, Magnification of three nearest-neighbour states after denoising. The current of each state was read by a constant voltage (0.2 V). No large-amplitude RTN was observed, and all of the states can be clearly distinguished. g, An individual memristor on the chip was tuned into 2,048 resistance levels by high-resolution off-chip driving circuitry, and each resistance level was read by a d.c. voltage sweeping from 0 to 0.2 V. The target resistance was set from 50 µS to 4,144 µS with a 2-µS interval between neighbouring levels. All readings at 0.2 V are less than 1 µS from the target conductance. Bottom inset, magnification of the resistance levels. Top inset, experimental results of an entire 256 × 256 array programmed by its 6-bit on-chip circuitry into 64 32 × 32 blocks, and each block is programmed into one of the 64 conductance levels. Each of the 256 × 256 memristors has been previously switched over one million cycles, demonstrating the high endurance and robustness of the devices.

Artificial Neuronal Devices Based on Emerging Materials: Neuronal Dynamics and Applications.

Artificial neuronal devices are critical building blocks of neuromorphic computing systems and currently the subject of intense research motivated by application needs from new computing technology and more realistic brain emulation. Researchers have proposed a range of device concepts that can mimic neuronal dynamics and functions. Although the switching physics and device structures of these artificial neurons are largely different, their behaviors can be described by several neuron models in a more unified manner. In this paper, the reports of artificial neuronal devices based on emerging volatile switching materials are reviewed from the perspective of the demonstrated neuron models, with a focus on the neuronal functions implemented in these devices and the exploitation of these functions for computational and sensing applications. Furthermore, the neuroscience inspirations and engineering methods to enrich the neuronal dynamics that remain to be implemented in artificial neuronal devices and networks toward realizing the full functionalities of biological neurons are discussed.

Plasma Phosphorylated Tau at Threonine 181 and Neuropsychiatric Symptoms in Preclinical and Prodromal Alzheimer Disease.

BACKGROUND AND OBJECTIVES: Plasma phosphorylated tau at threonine 181 (p-tau181), a well-validated marker of Alzheimer disease (AD) pathologic change, could be a more efficient way to diagnose AD than invasive or expensive biomarkers requiring CSF or PET. In some individuals, neuropsychiatric symptoms (NPS) are the earliest manifestation of AD, observed in advance of clear cognitive decline. However, the few studies assessing AD biomarkers in association with NPS have often had imprecision in capturing behavioral symptoms that represent sequelae of neurodegenerative disease. Thus, the mild behavioral impairment (MBI) construct was developed, framing NPS in a way to improve the precision of risk estimates for disease. MBI core criteria stipulate that NPS emerge de novo in later life and persist for at least 6 months. Here, cross-sectionally and longitudinally, we investigated associations of MBI with p-tau181, neuropsychological test performance, and incident AD. METHODS: Cognitively unimpaired and mild cognitive impairment (MCI) Alzheimer's Disease Neuroimaging Initiative participants were selected. MBI status was derived from the Neuropsychiatric Inventory (NPI) using a published algorithm. NPI total scores at baseline and year 1 visits were used to operationalize MBI (score >0 at both visits), NPS not meeting the MBI criteria (NPS-not-MBI, score >0 at only 1 visit), and no NPS (score = 0 at both visits). Linear regressions were fitted for cross-sectional analyses; multilevel linear mixed-effects and Cox proportional hazards models were implemented to examine the longitudinal associations of MBI with changes in p-tau181 and cognition and incident dementia. RESULTS: The sample included 571 participants (age 72.2 years, 46.8% female, 64.8% MCI). Cross-sectionally (ß = 8.1%, 95% CI 1.4%-15.2%, p = 0.02), MBI was associated with higher plasma p-tau181 levels compared with no NPS; NPS-not-MBI was not. Longitudinally, MBI was associated with higher p-tau181 (ß = 0.014%, 95% CI 0.003-0.026, p = 0.02), in addition to a decline in memory and executive function. Survival analyses demonstrated a 3.92-fold greater dementia incidence in MBI, with no significant differences between NPS-not-MBI and no NPS. DISCUSSION: These findings extend the evidence base that MBI is associated with elevated risk of cognitive decline and dementia and a sequela of emerging Alzheimer-related proteinopathies. MBI offers a substantial improvement over current approaches that explore behavior as a proxy marker for Alzheimer-related proteinopathies, with both clinical and AD trial enrichment implications.

Polymer-like Inorganic Double Helical van der Waals Semiconductor.

In high-performance flexible and stretchable electronic devices, conventional inorganic semiconductors made of rigid and brittle materials typically need to be configured into geometrically deformable formats and integrated with elastomeric substrates, which leads to challenges in scaling down device dimensions and complexities in device fabrication and integration. Here we report the extraordinary mechanical properties of the newly discovered inorganic double helical semiconductor tin indium phosphate. This spiral-shape double helical crystal shows the lowest Young's modulus (13.6 GPa) among all known stable inorganic materials. The large elastic (>27%) and plastic (>60%) bending strains are also observed and attributed to the easy slippage between neighboring double helices that are coupled through van der Waals interactions, leading to the high flexibility and deformability among known semiconducting materials. The results advance the fundamental understanding of the unique polymer-like mechanical properties and lay the foundation for their potential applications in flexible electronics and nanomechanics disciplines.

Higher platelet count, even within normal range, is associated with increased arterial stiffness in young and middle-aged adults.

BACKGROUND: Platelet counts and mean platelet volume (MPV) are related to cardiovascular disease, but a thorough investigation into the connection between increased arterial stiffness, MPV, and platelet counts is lacking. This study aimed to explore the association of platelet count and MPV with arterial stiffness in young and middle-aged adults. METHODS: A total of 2464 participants who underwent health checkups at National Cheng Kung University Hospital, Taiwan from November 2018 to December 2019 were included. We excluded participants aged <18 or >50 years; who are pregnant; on medication for dyslipidemia; with abnormal platelet count, incomplete data, and past history of hematologic disorders. We examined the association of platelet counts and MPV values with brachial-ankle pulse wave velocity (baPWV) levels and increased arterial stiffness. RESULTS: Platelet count was significantly higher in participants with increased arterial stiffness than in those without. The multiple linear regression model revealed that platelet counts were positively associated with baPWV levels (ß = 1.88, 95% confidence interval (CI): 0.96 to 2.80). In the binary logistic regression analysis, subjects in the higher platelet counts quartiles had a higher risk of developing increased arterial stiffness (Q2 vs. Q1: odds ratio (OR): 1.54, 95% CI: 1.05 to 2.27; Q3 vs. Q1: OR: 1.57, 95% CI: 1.06 to 2.33; and Q4 vs. Q1: OR: 2.23, 95% CI: 1.50 to 3.30). In contrast, MPV levels were not associated with arterial stiffness. CONCLUSIONS: Platelet count in midlife was positively associated with baPWV levels. Participants in higher platelet quartiles were at risk for increased arterial stiffness.

The Relationship Between Hearing and Mild Behavioral Impairment and the Influence of Sex: A Study of Older Adults Without Dementia from the COMPASS-ND Study.

Background: Hearing loss and mild behavioral impairment (MBI), both non-cognitive markers of dementia, can be early warning signs of incident cognitive decline. Objective: We investigated the relationship between these markers and reported the influence of sex, using non-dementia participants (n = 219; 107 females) from the Canadian Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND). Methods: Hearing was assessed with the 10-item Hearing Handicap for the Elderly-Screening (HHIE-S) questionnaire, a speech-in-noise test, screening audiometry, and hearing aid use. MBI symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Multivariable linear regressions examined the association between hearing and MBI symptom severity and multiple logistic regressions examined the association between hearing and MBI domains. Results: HHIE-S score was significantly associated with greater global MBI symptom burden, and symptoms in the apathy and affective dysregulation domains. Objective measures of audiometric hearing loss and speech-in-noise testing as well as hearing aid use were not associated with global MBI symptom severity or the presence of MBI domain-specific symptoms. Males were older, had more audiometric and speech-in-noise hearing loss, higher rates of hearing-aid use, and showed more MBI symptoms than females, especially apathy. Conclusion: The HHIE-S, a subjective self-report measure that captures emotional and social aspects of hearing disability, was associated with informant-reported global MBI symptom burden, and more specifically the domains of affective dysregulation and apathy. These domains can be potential drivers of depression and social isolation. Hearing and behavior change can be assessed with non-invasive measures, adding value to a comprehensive dementia risk assessment.

Arterial stiffness is associated with high-risk colorectal adenomas and serrated lesions: A cross-sectional study in a Taiwanese population.

BACKGROUND: Little is currently known about the association between arterial stiffness and colorectal serrated lesions. This study was aimed toward an investigation of the association between arterial stiffness and colorectal precancerous lesions, including colorectal adenomas and serrated lesions. METHODS: 7262 eligible adult subjects who underwent health check-ups with colonoscopies and brachial-ankle pulse wave velocity (baPWV) were recruited. Patients were categorized as polyp-free, low-risk and high-risk adenomas, and low-risk and high-risk serrated lesions based on the presence of polyps. The severity of arterial stiffness was categorized into four subgroups based on the baPWV quartile. RESULTS: After adjusting for multiple covariates, the baPWV values were found to be positively correlated with the occurrence of low-risk adenomas. With respect to high-risk polyps, the third and highest baPWV quartiles were significantly associated with the occurrence of both high-risk adenomas and high-risk serrated lesions. A more significant association was found in the highest baPWV quartiles combined with smoking in cases classified with high-risk serrated lesions. CONCLUSIONS: Increased arterial stiffness was independently associated with precancerous colorectal lesions, not only adenomas but also high-risk serrated lesions. Individuals with increased arterial stiffness, especially those who are smokers, should be more aware of the risk of colorectal cancer.

Dual-task gait and mild behavioral impairment: The interface between non-cognitive dementia markers.

BACKGROUND: Mild behavioral impairment (MBI) and dual-task gait cost (DTGC) are two non-cognitive markers of dementia that capture behavioral and motor symptoms. We investigated the relationship between MBI and DTGC in a sample of non-demented older adults. METHODS: This was a cross-sectional observational study of 193 participants (10 cognitively normal, 48 subjective cognitive decline (SCD), 135 mild cognitive impairment (MCI); 52.8% female) from 13 Canadian sites from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study. The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to define MBI severity using a published algorithm. DTGC, the percentage difference between dual-task and preferred walking speeds, was assessed under three cognitive tasks: animal naming, counting backwards, and serial seven subtractions. Associations were tested in the entire cohort and in the MCI subgroup using multivariable linear regression adjusted for age, sex, education, and diagnosis. The role of global cognition, executive function, verbal and working memory in the association were investigated using tests of mediation and moderation. RESULTS: MBI symptoms were present in 46.6% of participants (mean age = 72.4 years). Greater overall MBI burden was associated with lower gait speed across all conditions. Furthermore, a one-point increase in global MBI symptom severity was associated with a 0.8% increase in DTGC in the animal fluency condition, a 0.9% increase in the counting backwards condition and a 1.1% increase in the serial sevens condition. These associations were strongest in the subgroup of MCI participants. Executive function but not global cognition or verbal and working memory mediated the association between MBI and DTGC in all three conditions. CONCLUSIONS: MBI is associated with gait speed and DTGC in this group of non-demented individuals, independent of the presence or absence of MCI. These findings provide evidence of the relationship between these non-cognitive dementia markers of behavior and gait beyond cognitive impairment.

Plasma ß-Amyloid in Mild Behavioural Impairment - Neuropsychiatric Symptoms on the Alzheimer's Continuum.

INTRODUCTION: Simple markers are required to recognize older adults at higher risk for neurodegenerative disease. Mild behavioural impairment (MBI) and plasma ß-amyloid (Aß) have been independently implicated in the development of incident cognitive decline and dementia. Here we studied the associations between MBI and plasma Aß42/Aß40. METHODS: Participants with normal cognition (n = 86) or mild cognitive impairment (n = 53) were selected from the Alzheimer's Disease Neuroimaging Initiative. MBI scores were derived from Neuropsychiatric Inventory items. Plasma Aß42/Aß40 ratios were assayed using mass spectrometry. Linear regressions were fitted to assess the association between MBI total score as well as MBI domain scores with plasma Aß42/Aß40. RESULTS: Lower plasma Aß42/Aß40 was associated with higher MBI total score (p = 0.04) and greater affective dysregulation (p = 0.04), but not with impaired drive/motivation (p = 0.095) or impulse dyscontrol (p = 0.29) MBI domains. CONCLUSION: In persons with normal cognition or mild cognitive impairment, MBI was associated with low plasma Aß42/Aß40. Incorporating MBI into case detection may help capture preclinical and prodromal Alzheimer's disease.

A Four-Step Cascade Drug-Release Management Strategy for Transcatheter Arterial Chemoembolization (TACE) Therapeutic Applications.

The purpose of this study was to develop a four-step cascade drug-release system for transcatheter arterial chemoembolization (TACE) therapeutic applications according to disease-driven and patient-focused design theories. The four steps underlying these strategies involve the blockage of nutrient supply, nanoparticles, codelivery and the cell cytotoxic effect. Calibrated spherical gellan gum (GG) and nanoparticle-containing gellan gum microspheres were prepared using a water-in-oil emulsification method. Self-assembled nanoparticles featuring amine-functionalized graphene oxide (AFGO) as the doxorubicin (Dox) carrier were prepared. The results confirm that, as a drug carrier, AFGO-Dox nanoparticles can facilitate the transport of doxorubicin into HepG2 liver cancer cells. Subsequently, AFGO-Dox was introduced into gellan gum (GG) microspheres, thus forming GG/AFGO-Dox microspheres with a mean size of 200-700 µm. After a drug release experiment lasting 28 days, the amount of doxorubicin released from 674 and 226 µm GG/AFGO-Dox microspheres was 2.31 and 1.18 µg/mg, respectively. GG/AFGO-Dox microspheres were applied in a rabbit ear embolization model, where ischemic necrosis was visible on the ear after 12 days. Our aim for the future is to provide better embolization agents for transcatheter arterial chemoembolization (TACE) using this device.

Cumulative tea consumption is inversely associated with colorectal adenomas in adults: A cross-sectional study in a Taiwanese population.

PURPOSE: This study examined the association between cumulative tea consumption over time and various colorectal adenomas as well as their pathology, number, and size. METHODS: 7355 eligible subjects who underwent health check-ups with colonoscopies were recruited. They were classified into three groups: polyp-free, having low-risk colorectal adenomas, and having high-risk colorectal adenomas. The adenoma pathology, number, and size were collected. We defined 120 mL for each Chinese traditional teapot as a 'cup', and calculated the average daily cups of tea consumed. A 'cup-year' was defined as the daily cups multiplied by the years of tea consumption and was used to express the cumulative amount of tea consumption over time. RESULTS: Compared to those with no habitual tea consumption, the lowest, middle, and highest tertiles of tea consumption were found to be inversely related to low-risk colorectal adenomas. For high-risk colorectal adenomas, a negative association was found only in the group with the highest tertile of tea consumption. An inverse association between the highest tertile of tea consumption and various features of high-risk colorectal adenomas was also found for villous-rich adenomas and the presence of three or more adenomas, but was not found to be related to adenoma size ≥1 cm. CONCLUSION: Tea drinking was inversely associated with both low-risk and high-risk colorectal adenomas. Only a larger cumulative dose of ≥42 cup-years was negatively associated with high-risk colorectal adenomas, especially adenomas with villous-rich pathology and when three or more adenomas were present.

White matter hyperintensities and mild behavioral impairment: Findings from the MEMENTO cohort study.

Background: White matter hyperintensities (WMH) contribute to cognitive decline and increase risk for dementia. Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by the emergence and persistence of neuropsychiatric symptoms (NPS) in later life as an at-risk state for incident cognitive decline and dementia. Both WMH and MBI are common in patients with mild cognitive impairment (MCI), but few studies have established the link between these two risk markers in this population. Methods: Participants were memory clinic patients with MCI from the French MEMENTO study. WMH volume was quantified using brain magnetic resonance imaging. Participants were categorized into MBI+ and MBI- status based on NPS persistence, and the association between MBI status and domains with WMH volume was assessed with linear regression. Results: A total of 768 participants [mean age 72.8 (SD=8.00); 57% female] were included. MBI (i.e., persistent NPS) was present in 229 participants (29.8%). MBI+ status was significantly associated with lower MMSE score and male sex. Compared to MBI-, MBI+ status was associated with 9.4% higher WMH volume [p = 0.01 (95% CI 2.0% to 16.7%)]. In this model, MMSE score was not associated with WMH volume. None of the MBI domains individually predicted greater WMH volume, although emotional dysregulation, impulse dyscontrol, and apathy trended towards significance. Conclusions: In a memory clinic sample of older adults with MCI, MBI was associated with higher WMH volume. Global MBI status outperformed MMSE and individual MBI domains, supporting the utility of MBI, a multi-NPS-domain composite assessment, for predicting WMH volume.