bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of structural MRI with Braak staging using neural network‐based risk scoring
Authors: Miller Matthew I. , Qiu Shangran , Joshi Prajakta S. , Lee Joyce , Au Rhoda , Kolachalama Vijaya B. 
Published: June 2023

AbstractBackgroundThe gold standard of Alzheimer’s disease (AD) diagnosis remains histopathologic examination of neuropathologic changes. However, the dependence on post‐mortem microscopic analysis limits the role of pathology in clinical care. Magnetic resonance imaging (MRI) is routinely used to diagnose suspected dementia (DE) due to AD, but correlating neuroimaging to underlying pathologic changes remains challenging. Herein, we report the development of two risk scores derived from convolutional neural network (CNN) processing of MRI scans, which we then validate against Braak staging of neurofibrillary tangles from autopsy reports.MethodUsing T1‐weighted MRIs from the National Alzheimer’s Coordinating Center (NACC), we trained two CNNs (Figure 1) to predict continuous scores for overall cognitive status (“COG” score) and AD probability (“ALZ” score). The COG score, ranging from 0‐2, graded a subject’s cognitive status on a spectrum from normal cognition (NC, 0), to mild cognitive impairment (MCI, 1), and DE due to any cause (2). The ALZ score then graded each DE individual’s probability of AD from 0 to 1. These CNNs were then applied to a subset of participants with autopsy reports available within 6 months of MRI. CNN performance was evaluated by area under receiver operating characteristic curve (AUC). Differences in risk scores were assessed by Kruskal‐Wallis H testing with post hoc Dunn testing.ResultThe CNN models for COG and ALZ score estimation were trained on 4,822 NACC participants. Thresholding of COG scores distinguished individuals with DE from those with NC and MCI (AUC = 0.87). ALZ scores distinguished individuals with AD from those with non‐AD causes of DE (AUC = 0.77). Among 74 persons with available neuropathology data, COG scores differed significantly among Braak staging groups (p<0.001), increasing from a mean of 0.99±0.36 in Stage 1 to 1.47±0.41 in Stage 6 (p = 0.010). Significant differences in ALZ scores were also observed (p = 0.039) between varying Braak stages (p = 0.039), increasing from a mean of 0.69±0.42 in Stage 1 to 0.91±0.29 in Stage 6 (p = 0.046) (Figure 2).ConclusionCNN processing of MRI scans may derive continuous risk scores for grading cognitive status and AD risk. This novel approach may offer practitioners a computational tool to improve AD diagnosis.
Outcome measures of cognitive gain in clinical trials of patients with primary central nervous system infections: A systematic review
Authors: Rizvi Syeda Taliya , Shah Jhankhana , Shaaya Sarah , Mollayeva Tatyana 
Published: June 2023

AbstractBackgroundPrimary central nervous system (CNS) infections are often accompanied with cognitive deficits. Cognitive deficits are assessed by a wide range of outcome measures to determine the severity of deficits and their response to intervention. The aim of this review was to provide description of outcome measures used to assess cognitive function in patients with primary CNS infections enrolled in clinical trials.MethodWe searched MEDLINE, Embase, and CENTRAL from inception to October 2022 to identify clinical trials that enrolled patients with cognitive deficits due to primary CNS infections. All outcome measures evaluating cognitive function in these clinical trials were considered. Outcome measure was defined as any standardized measure evaluating one or more of the six cognitive domains: complex attention, executive functioning, learning and memory, language, perceptual‐motor ability, and social cognition.ResultEight randomized controlled trials (RCTs) and one pre‐post intervention study enrolled patients with Lyme disease (infectious agent bacterium borrelia burgdorferi), herpes simplex virus type 1 (infectious agent herpes simples virus), and Creutzfeldt–Jakob disease (infectious agent prion). Within these clinical trials, 29 outcome measures were utilized to evaluate change in cognitive function in response to treatment with antibiotics (five studies), antiviral (three studies), or non‐opioid analgesic (one study). Out of all outcome measures, only two assessed all six cognitive domains: Penn computerized neurocognitive battery and Wechsler Adult Intelligence Scale; the remaining evaluated one or several cognitive domains using a variety of measures. The three most frequently evaluated cognitive domains were complex attention (19 distinct outcome measures within nine studies), executive functioning (19 distinct outcome measures within eight studies) and perceptual‐motor ability (16 distinct outcome measures within eight studies). The least evaluated cognitive domain was social cognition (four distinct outcome measures within four studies).ConclusionClinical trials included in this review were designed to improve cognitive function in patients with primary CNS infection. Selection of outcome measures that have been previously used is desirable as it would allow between‐study comparisons. Assessment of social cognition is important to consider. Evaluations using multiple outcome measures might be tiring and intrusive to patients, and therefore implications of practical constraints should be tested.
Racial disparities in advance care planning and end‐of‐life care preferences among decedents in the health and retirement study (2002‐2019)
Authors: Rahemi Zahra , Cidav Tom , Malatyali Ayse , Montaner Olga F Jarrín , Dye Cheryl 
Published: June 2023

AbstractBackgroundAlzheimer’s Disease and Related Dementias (ADRD) is more prevalent among racial/ethnic minority older adults who also experience disparities in end‐of‐life care quality. The rate and timing of advance care planning conversations among individuals living with ADRD vary by race/ethnicity and other sociodemographic factors. As cognitive impairment progresses, caregivers, communities, and healthcare providers face challenges related to end‐of‐life care planning and management. Early advance care planning provides the opportunity to align care management with the wishes of the patients with ADRD. Our purpose was to examine EOL care preferences and ACP in racial minority ADRD patients.MethodThe Health and Retirement Study (HRS) Exit files (2002‐2019) were used to conduct a descriptive analysis of advance care planning and end‐of‐life care preferences among decedents.ResultOf the 7,214 decedents from the HRS sample, 13% had a diagnosis of dementia, 30% were cognitively impaired but not diagnosed with dementia, and 57% were cognitively intact. The results showed significant relationships between cognitive functioning, race, gender, and marital status. The mean cognitive impairment scores were worse for racial/ethnic minority participants compared to white participants, women compared to men, and widowers compared to married participants.Among the 3,102 participants with cognitive impairment or ADRD diagnosis, Black participants were 78.5% less likely to have a living will and 57.8% less likely to have a discussion about end‐of‐life care compared to non‐Hispanic white participants. Similarly, participants of other racial minority groups were 88% less likely to have a living will and 57.5% less likely to have an end‐of‐life discussion compared to white participants. Gender and marital status were not significant predictors of having discussed end‐of‐life care preferences. In terms of end‐of‐life care preferences, Black participants were 3.29 times more likely to prefer all possible end‐of‐life care and 66% less likely to refuse extensive care measures compared to white participants.ConclusionBlack older adults with ADRD had lower rates of advance care planning and preferred intensive care measures vs. comfort care compared to their white counterparts. Recognition of these differences can inform the design and provision of interventions and educational programs to improve equity in end‐of‐life care.
Applicability of an actuarial neuropsychological method to diagnose mild cognitive impairment in a diverse sample
Authors: Carlew Anne R , Goette William , Schaffert Jeffrey , Rossetti Heidi , Lacritz Laura 
Published: June 2023

AbstractBackgroundThe Jak/Bondi actuarial neuropsychological method for detection of mild cognitive impairment (MCI) has been shown to identify subjects less likely to revert to normal and more likely to have Alzheimer’s Disease (AD) biomarkers compared to conventional clinical methods. Various iterations of this method have been applied to datasets of predominately White, highly‐educated participants, limiting generalizability to more diverse cohorts. This project investigated the applicability of the actuarial MCI diagnostic method to the Texas Alzheimer’s Research and Care Consortium (TARCC) cohort.MethodAll subjects from the TARCC cohort with expert consensus diagnoses of normal control (NC) and MCI at baseline (n = 1911; 65.72% female; 47.11% Hispanic; Mage = 67.49; Medu = 12.80) were re‐classified as NC or MCI using actuarial criteria of 2 impaired (>1 SD below normative mean) tests in any of 4 cognitive domains OR 1 impaired test in at least 3 cognitive domains. The clinically‐diagnosed MCI (MCIc) sample (n = 655; 58.47% female; 42.44% Hispanic; Mage = 71.34; Medu = 13.01) and the actuarially‐diagnosed MCI (MCIa) sample (n = 837; 71.21% female; 68.82% Hispanic; Mage = 66.30; Medu = 10.87) were separately submitted to cluster analysis. McNemar’s test was used to investigate frequency of APOE4 allele by diagnostic group.ResultCluster analysis of the MCIa group yielded 3 distinct clusters: a purely amnestic cluster (n = 332), a primary language‐impaired cluster (n = 381), and a multidomain/mixed cluster (n = 124). The MCIc group yielded 2 clusters: a multidomain/mixed cluster (n = 538), and a cognitively normal cluster (n = 117). The MCIc cases were significantly more likely to have APOE4 alleles (33% vs. 28% of MCIa group).ConclusionSimilar to previous research, the MCIa group fell into 3 distinct cognitively‐impaired groups. Despite 18% of MCIc participants falling in a “cognitively‐normal” cluster, MCIc subjects were more likely to have the AD biomarker APOE4. These findings warrant further investigation, particularly in relation to ethnicity, as individuals of Hispanic origin are less likely to carry APOE4 alleles, and APOE4 confers less AD risk in Hispanics compared to non‐Hispanic Whites. Future research will investigate the prognostic utility of the actuarial method for racial/ethnic minorities using cognitive and functional longitudinal data.
The link between apathy and depressive symptoms and healthy lifestyles in older community‐dwelling adults
Authors: Harrison Fleur , Brodaty Henry , Mortby Moyra E , Aerts Liesbeth , Guastella Adam J 
Published: June 2023

AbstractBackgroundApathy (loss of motivation or goal‐directed behaviour) and depression each confer risk for dementia, cardiovascular disease and mortality in older adults. The mechanisms by which these neuropsychiatric symptoms are linked with health outcomes are not yet understood. Health behaviours may be one pathway, yet their potential links with apathy have received scant attention, whereas depression has been consistently associated with unhealthier behaviours including physical inactivity. Depression and apathy may be confounded, thus it is critical to determine their potential differential associations with health behaviours. This study thus aims to investigate whether apathy and depressive symptoms in older adults were associated with a broad battery of health behaviours.MethodCommunity‐dwelling participants from the Sydney Memory and Ageing Study (n = 1,030) aged 70‐90 without dementia completed assessments including the Geriatric Depression Scale, from which apathy (GDS‐3A) and depression (GDS‐12D) subscores were obtained. To investigate cross‐sectional associations with self‐reported physical activity, diet, current and lifetime alcohol consumption and smoking, linear or logistic regressions predicted the outcomes from apathy and depression, controlling for age, sex, education, global cognition and chronic conditions.ResultGreater apathy (but not depressive symptoms) was significantly associated with current physical inactivity (fewer hours/week weighted by intensity, p < .001) and frequent alcohol consumption (>2x weekly, p <.05). Depressive symptoms alone predicted poorer current adherence to Australian Dietary Guidelines (ADG‐2013, p <.05) and smoking (p <.001). Higher levels of both apathy and depressive symptoms were significantly associated with a past period of “heavier” alcohol consumption (p <.05); neither were related with lifetime history of smoking nor lifetime abstinence from alcohol.ConclusionApathy and depression were differentially associated with health behaviours. Presence of these symptoms in older adults may act as a barrier to engagement in healthier lifestyle activities, which are known to have numerous benefits for health and cognitive outcomes. These novel findings should be further examined longitudinally and with objective measures and alternative apathy assessment. Apathy should be considered along with depression as key determinants of health behaviours when designing health promotion interventions targeting older adults, and in models of dementia risk reduction.
Relationship of APOE genotypes and level of cognitive reserve to cognitive trajectories among cognitively normal individuals
Authors: Pettigrew Corinne , Soldan Anja , Nazarovs Jurijs , Singh Vikas , Wang Jiangxia , Gross Alden L , Johnson Sterling C. , Masters Colin L , Maruff Paul , Morris John C , Hassenstab Jason J. , Resnick Susan M. , Albert Marilyn 
Published: June 2023

AbstractBackgroundPrior findings indicate that both genetic factors and indices of cognitive reserve (CR) influence risk of cognitive decline, with APOE4 genetic status increasing risk, and APOE2 genetic status and higher CR indices decreasing risk. However, it remains unclear whether these genetic and lifestyle variables interact to influence long‐term cognitive trajectories. This study examined whether these variables modify baseline cognitive scores and longitudinal cognitive trajectories in N = 1819 participants who were cognitively normal at baseline and included in the Preclinical AD Consortium (PAC).MethodPAC datasets include harmonized data from five longitudinal cohort studies: ACS, AIBL, BIOCARD, BLSA, and WRAP. Longitudinal cognitive performance was measured by harmonized factor scores for global cognition, memory, and executive function (M follow‐up = 9.8y; Table 1). APOE genotypes were coded with separate indicator variables for APOE2 (n = 233) and APOE4 (n = 581), with APOE3/3 (n = 1005) as the reference group. A CR index was calculated by combining years of education and literacy scores.ResultIn longitudinal mixed effect models, using time since baseline as the timescale (Table 2), higher CR index scores were associated with better baseline cognitive performance for all cognitive factor scores, but not with rate of change in cognition over time. In contrast, APOE4 genotype was associated with more negative rates of cognitive change. For the global and memory scores, there were also 3‐way CR index x APOE4 x time interactions, indicating the negative effect of APOE4 genotype on global and memory score change was attenuated among individuals with higher CR index scores (Figure 1). When the models were re‐run with the term for APOE4 genetic status reflecting the number of APOE4 alleles (i.e., 0, 1, 2; Table 3), the patterns of results were similar, except the 3‐way CR index x APOE4 x time interaction for global cognition was only marginal (p = 0.06).ConclusionHigher CR proxy scores are associated with higher levels of cognitive performance, whereas APOE4 genetic status is associated with greater rates of cognitive decline. Higher levels of CR may attenuate APOE4‐related declines in global cognition and memory, but level of CR and APOE4 have largely independent effects on executive function.
Sex‐specific association of physical frailty and cognitive function in a population‐based cross‐sectional study of American older adults
Authors: Karanth Shama D 
Published: June 2023

AbstractBackgroundWe hypothesized that the association between physical frailty and cognition would be modified by participant sex in a nationally representative sample of elderly adults in the United States.MethodsCross‐sectional data from the National Health and Nutrition Examination Survey (NHANES 2011‐2014) were obtained for participants age ≥60 years. Physical frailty was defined by four measures developed by Fried et al.: exhaustion, weakness, low body mass, and low physical activity, and then categorized into robust (None), pre‐frail (1‐2 measures), or frail (3‐4 measures). Cognitive test scores were converted to z‐scores based on the study sample means and standard deviations. To estimate global cognition, a composite z‐score was calculated by averaging the individual z‐scores. Linear regression models were fit to evaluate the association between frailty and cognition. In addition to the cognitive tests, we evaluated frailty as a risk factor for self‐reported memory complaint (SMC) using logistic regression. We used sampling weights to account for the NHANES design.ResultsA total of 2863 participants aged 60 years or older were included. According to the 4‐items frailty measures, 50.5% of participants were robust, 44.7% were pre‐frail, and 4.8% were frail. The majority of the participants were > 70 (58.9%), women (54.4%), and White (79.4%). After adjustment for age, sex, race/ethnicity, education, alcohol use, income, marital status, diabetes, hypertension, and history of stroke, compared to robust, being frail (β = ‐0.69, 95%CI: ‐0.90, ‐0.48) and pre‐frail (β = ‐0.11, 95%CI: ‐0.19, ‐0.02) was associated with lower global cognitive z‐scores. Compared to men, pre‐frail women had mean adjusted global cognitive z‐scores that were ‐0.33 standard deviations lower (95% confidence interval (CI): ‐0.23, ‐0.42; P<0.001). Similarly, compared to frail men, frail women had mean adjusted global z‐scores that were lower but the difference was not significant. There were no significant differences in odds of SMC by sex with regard to frailty.ConclusionsIn this population‐based cohort, our findings suggest frailty was associated with lower cognitive performance in older adults and modified by sex. Participants who did not meet criteria for 3‐4 measures of frailty but had 1‐2 measures showed similar lower cognitive performance.
The effect of brain exercise for improving cognitive function among cognitively impaired batik workers: A preliminary study in Indonesia
Authors: Wulandari Clara Valencia Okky , Prodjohardjono Astuti , Satiti Sekar , Vidyanti Amelia Nur 
Published: June 2023

AbstractBackgroundBrain exercise, also known as Brain Gym, aims to maintain brain health by exercising. The movements in brain exercise are focused to train contralateral and ipsilateral coordination, namely by doing hand and foot movements on different sides and the same side alternately. Brain exercise can restore the reticular activating system in the brain so that it can improve memory abilities. This study aimed to identify the effect of brain exercise for improving cognitive function among batik workers who had cognitiveMethodThis study was one group pretest and posttest design. We conducted brain exercise on 47 batik workers with cognitive impairment who were chronically exposed to heavy metals in 2 batik centers in Gulurejo Village, Lendah, Kulonprogo, Indonesia. Subjects were examined for cognitive function before treatment using MoCA‐INA (Montreal Cognitive Assessment‐Indonesia version). The treatment of brain exercise was done 2 times a week for 3 months, with duration of exercise was 10 minutes. The cognitive function of the research subjects was re‐examined after 1 and 3 months of brain exercise.ResultThe mean age of the subject was 44 years‐old, with the median duration of being batik worker was 4 years (1‐15 years). The mean MoCA‐Ina score before treatment was 19.21 ± 4.86. After 1 month of treatment, there was an increase of MoCA‐INA score to 19.91 ± 4.81. After 3 months of treatment, the MoCA‐INA score futher increased to 22.45 ± 4.74. When further analyzed for each domain, we found that there were no differences after 1 month. However, there was a significant increase in the domains of attention (p = 0.004), language (p = 0.002), abstraction (p = 0.10), delayed recall (p < 0.001) and orientation (p = 0.001) after 3 months exercise.ConclusionBrain exercise may benefit for improving cognitive function among batik workers with cognitive impairment. This study could potentially be applied for other population with dementia to help improving the clinical outcome.
Longitudinal Changes in Insulin Resistance, Cognition, and AD Biomarkers across the AD Continuum
Authors: Klinedinst Brandon S , Pappas Colleen , Larsen Brittany A , Willette Sara A , Wang Qian , Pollpeter Amy , Li Tianqi , Lim Ye‐Lim , Cerna Jonathan , Willette Auriel A 
Published: June 2023

AbstractBackgroundTo determine if 3‐year changes in serum insulin resistance (IR) were related to changes in brain volume and glucose uptake, cognition, and CSF biomarkers in cognitively unimpaired and impaired older adults.MethodAlzheimer’s Disease Neuroimaging Initiative data was downloaded for 275 aged adults (55‐89 years). Participants had longitudinal T1‐ and T2‐weighted volume scans, fluorodeoxyglucose (FDG) scans, CSF β‐amyloid (Aβ) and tau species, and cognitive performance over baseline and months 6, 12, 18, 24, and 36. Growth curve modeling in R regressed IR against these outcomes, by itself and with clinical diagnosis as a moderator. Cognitively unimpaired (CU) adults were used as a reference group to determine potential effects in pathological aging.ResultIn AD and/or Mild Cognitive Impairment progressors to AD (MCI‐P), higher IR over time was related to progressive atrophy in medial temporal frontoinsular areas. Similarly, decline was seen in global cognition and both memory and executive function. HOMA1‐IR associations were partially mediated by p‐tau‐181. Among clinical diagnosis groups, higher IR was significantly related to amyloid, p‐tau‐181, and total tau 181 among AD patients but not MCI or unimpaired groups.ConclusionThese findings suggest that in older adults who develop AD or had AD at baseline, higher IR over time is related to brain atrophy and consequent cognitive decline, perhaps as a function of amyloid or tau deposition.
Triptycene‐Fused Sterically Shielded Multi‐Resonance TADF Emitter Enables High‐Efficiency Deep Blue OLEDs with Reduced Dexter Energy Transfer
Authors: Mubarok Hanif , Amin Al , Lee Taehwan , Jung Jaehoon , Lee Jeong‐Hwan , Lee Min Hyung 
Published: June 2023

AbstractDesigning multi‐resonance (MR) emitters that can simultaneously achieve narrowband emission and suppressed intermolecular interactions is challenging for realizing high color purity and stable blue organic light‐emitting diodes (OLEDs). Herein, a sterically shielded yet extremely rigid emitter based on a triptycene‐fused B,N core (Tp‐DABNA) is proposed to address the issue. Tp‐DABNA exhibits intense deep blue emissions with a narrow full width at half maximum (FWHM) and a high horizontal transition dipole ratio, superior to the well‐known bulky emitter, t‐DABNA. The rigid MR skeleton of Tp‐DABNA suppresses structural relaxation in the excited state, with reduced contributions from the medium‐ and high‐frequency vibrational modes to spectral broadening. The hyperfluorescence (HF) film composed of a sensitizer and Tp‐DABNA shows reduced Dexter energy transfer compared to those of t‐DABNA and DABNA‐1. Notably, deep blue TADF‐OLEDs with the Tp‐DABNA emitter display higher external quantum efficiencies (EQEmax=24.8 %) and narrower FWHMs (≤26 nm) than t‐DABNA‐based OLEDs (EQEmax=19.8 %). The HF‐OLEDs based on the Tp‐DABNA emitter further demonstrate improved performance with an EQEmax of 28.7 % and mitigated efficiency roll‐offs.