bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining Automatic Generated Language Features of Chinese Spontaneous Speech for Early Detection of Cognitive Decline
Authors: Wang Yi‐Hsuan , Chou Chia‐Ju , Liu Yi‐Chien , Lee Chia‐Ying , Chang Ya‐Ning 
Published: December 2023

AbstractBackgroundConnected speech is sensitive on detecting cognitive decline in early Alzheimer disease. In this study, we apply artificial intelligence to develop an automatic assessment for analyzing speech data.Method79 samples of picture description speech data were collected. All participants were native Chinese speakers including 31 normal controls (59‐88 yrs) and 49 patients (amnestic mild cognitive impairment and early Alzheimer’s disease) (58‐88 yrs). We extracted 16 linguistic features from the manually transcribed text. These linguistic features were generated by well‐trained linguists or automatically processed by the machine. We also trained decision tree models with those two sets of linguistic features. Seventy percent of the data was used for training and the remainder was used for testing. We also applied a cross‐validation method to avoid overfitting.ResultTotal words, unique words, and content words generated from linguists or machines were highly correlated (about r = 0.99, p < .001). However, the correlations between verb ratio, mean length of sentences, and filler ratio were relatively low (about r = 0.75, p < .001). With manually corrected features, the model could achieve 91.67% accuracy. Among them, the pronoun ratio and MLU (mean length of utterance) appeared to be equally crucial for model prediction. By contrast, with automatically generated features, the model achieved 83.33% accuracy only. MLU and MLS (mean length of sentences) were essential features for prediction.ConclusionAutomatic assessment could also achieve a good accuracy rate compared to humans (83.33% v.s. 91.67%). Some linguistic features such as fillers or sentences were still highly dependent on the expert’s judgment. Interestingly, MLU was critical in the prediction model of automatic or experts.
The effect of the Home‐based tDCS on behavioral and electrophysiological parameters in patients with both MCI and depression: A randomized double‐blind placebo‐controlled trial
Authors: Kim Do Hoon , Moon Yoo Sun 
Published: December 2023

AbstractAs depressive symptom is considered as a prodrome, a risk factor of progression from mild cognitive impairment (MCI) to dementia, improving depressive symptoms should be considered a clinical priority in transcranial direct current stimulation (tDCS) intervention in patients with MCI. We aimed to comprehensively evaluate the efficacy of the home‐based and remotely monitored tDCS in patients with both MCI and depression, by integrating cognitive, psychological, and electrophysiological indicators. In a 6‐week, randomized, double blind and sham‐controlled study, thirty‐seven community‐dwelling patients were randomly assigned to either an active or a sham stimulation group, and received 30 home‐based session of 2 mA tDCS for 30 min located anode over left and cathode over right dorsolateral prefrontal cortex. We measured depressive symptoms, neurocognitive function, and resting‐state electroencephalography (EEG). Active tDCS was not significantly different from sham tDCS in the effects of both depressive symptoms and cognitive functions. However, compared to sham stimulation, active tDCS decreased and increased the activation of delta and beta frequencies, respectively. Moreover, the increase in beta activity was correlated with the cognitive enhancement only in the active group. It was not possible to reach a definitive conclusion regarding the efficacy of tDCS on depression and cognition in patients with both MCI and depression. Nevertheless, the relationship between the changes of electrophysiology and cognitive performance suggests potential neuroplasticity enhancement implicated in cognitive processes by tDCS.
Efficacy of a mobile based multidomain intervention to improve cognitive functions and health related outcomes among Korean older adults with a high risk of dementia
Authors: Chung Ji Yeon , Lee Jaegyeong , Kim Junhyoung , Park Ayeong , Hong Rak‐Kyeun , Heo Mina , Lim Da‐Hye , Kim Hoowon , Ko Myungjin 
Published: December 2023

AbstractBackgroundSubjective cognitive decline is a self‐reported experience of declining cognitive function showing normal performance in cognitive assessments, which is a known risk factor for dementia. Recent studies highlight the importance of nonpharmacological multidomain interventions that can target multiple risk factors of dementia in older adults. We investigated the efficacy of the Silvia program, a mobile‐based multidomain intervention, to improve cognitive function and health‐related outcomes of older adults with a high risk of dementia. Additionally, we compared its effects to a conventional paper‐based multidomain program on various health indicators related to risk factors of dementia.MethodThis prospective randomized controlled trial involved 77 older adults with a high risk of dementia recruited from the Dementia Prevention and Management Center in Gwangju, South Korea during May to October 2022. Participants were randomly assigned to either the mobile‐ or paper‐based group. Interventions were administered for 12 weeks, where pre‐ and post‐assessments were conducted.ResultThe Korean version of the Repeatable Battery for the Assessment of Neuropsychological status (K‐RBANS) total score did not show significant differences between groups. The mobile group showed better improvement in K‐PRMQ scores and PSS scores than the paper group. Differences within groups showed that mobile‐based interventions significantly improved the Korean version of the prospective and retrospective memory questionnaire (K‐PRMQ), State‐Trait Anxiety Inventory‐X‐1 (STAI‐X‐1), Perceived Stress Scale (PSS), and e EuroQoL 5‐Dimension 5‐Level (EQ‐5D‐5L) scores, while paper‐based interventions significantly improved PSS, and EQ‐5D‐5L scores.ConclusionThe Silvia program was more effective than paper‐based intervention in improving self‐reported memory failures, stress, anxiety, and health‐related quality of life. However, longer periods of administration for more than 12 weeks may be needed to achieve significant improvements in cognitive function by objective measures
Associations between normal cognitive aging and neurodegeneration
Authors: Hemminghyth Mathilde Suhr , Breitve Monica Haraldseid , Rongve Arvid , Chwiszczuk Luiza J. , Fladby Tormod , Kirsebom Bjørn‐Eivind 
Published: December 2023

AbstractBackgroundMultiple cognitive domains, including learning, memory and psychomotor speed, show significant reductions with age. These changes are thought to reflect normal cognitive aging. However, since cerebrospinal fluid (CSF) neurodegenerative biomarkers, such as total‐tau (t‐tau) and Neurofilament light chain (NfL), also show age‐related increases in normal aging, we aimed to investigate whether age‐associated cognitive decline may be mediated by age‐associated neurodegenerative changes.MethodWe included 114 cognitively healthy participants aged 40‐80 years from The Norwegian Dementia Disease Initiation Study. All had normal concentrations of CSF Aβ42/40 ratio. Cognitively healthy was defined as demographically adjusted T‐scores ≥35 on standardized cognitive tests. We fitted mediation models using structural equation modelling (SEM), with either CSF NfL or t‐tau as a mediator between age and CERAD learning, CERAD recall, TMT‐A and TMT‐B. All variables were standardized prior to analyses; in addition, both t‐tau and NfL were log transformed due to skewness.ResultsSee table 1 for demographic and clinical characteristics. Whilst neither NfL nor t‐tau showed statistically significant mediation of age‐related cognitive decline, our results nevertheless suggest a partial mediation of NfL on age‐related cognitive decline. Here, relationships between age and CERAD learning, CERAD Recall, and TMT‐A performance were weakened whereas higher NfL was associated with worse performance, in particular for delayed memory recall. This was not observed for t‐tau in any models. See figure 1‐2.ConclusionAge‐related decline in verbal learning, memory and psychomotor speed may be partially attributable to NfL‐associated neurodegenerative changes in cognitively healthy adults. As NfL reflects axonal degeneration, these results may reflect white matter neurodegeneration in aging.
Entraining brain oscillatory activity at alpha frequencies in dementia with Lewy bodies
Authors: Benussi Alberto , Cantoni Valentina , Rivolta Jasmine , Gadola Yasmine , Zoppi Nicola , Padovani Alessandro , Borroni Barbara 
Published: December 2023

AbstractBackgroundDementia with Lewy bodies (DLB) is characterized by a marked shift of electroencephalographic (EEG) power and dominant rhythm, from the alpha towards the theta frequency range. Transcranial alternate current stimulation (tACS) is a novel non‐invasive brain stimulation technique that allows entrainment of cerebral oscillations at desired frequencies. The objective of the present study was to evaluate safety and efficacy of occipital alpha tACS in DLB patients.MethodWe performed a double‐blind, randomized, sham‐controlled, cross‐over clinical trial in 12 DLB patients. Patients were randomized to receive real (60 minutes of 3 mA peak‐to‐peak stimulation at 12 Hz) or sham stimulation over the occipital cortex (Oz according to the 10‐20 international EEG system). Patients underwent clinical evaluation (clock‐drawing test, trail‐making test part A and B, the quantitative pentagon drawing test subitem), neurophysiological assessment (short‐latency afferent inhibition to evaluate cholinergic circuits) and EEG recordings, at baseline and after real/sham stimulation.ResultOccipital alpha tACS was safe and well tolerated in all patients. We observed a significant increase in clinical performance scores, in neurophysiological measures of cholinergic transmission and in occipital alpha power spectrum density after real stimulation but not sham stimulation.ConclusionOccipital tACS delivered at alpha frequencies may be a novel therapeutic approach in patients with DLB.
Biochemical and molecular heterogeneity of human TDP‐43 proteinopathies in age‐related dementias
Authors: Porta Sílvia 
Published: December 2023

AbstractThe deposition of TAR DNA‐binding protein 43 (TDP‐43), especially phosphorylated TDP‐43 (pTDP‐43), into cytoplasmic and intranuclear inclusions is the pathological hallmark of frontotemporal lobar degeneration (FTLD‐TDP) and amyotrophic lateral sclerosis (ALS). Such TDP‐43 inclusions are also a common comorbid pathology in other neurodegenerative diseases, including Alzheimer’s disease (AD) and Limbic‐predominant Age‐related TDP‐43 Encephalopathy (LATE). The stereotypical distribution of TDP‐43 pathology in FTLD‐TDP/ALS as the disease progresses suggests a hierarchical regional spreading of TDP‐43 aggregates over time. Although the mechanisms underlying progression in these diseases are still unknown, increasing evidence supports a model where misfolded proteins released from a cell harboring pathological inclusions act on recipient cells to form de novo pathology by corrupting normal endogenous proteins to adopt pathological conformations. In vitro studies have shown cell‐to‐cell transmission of TDP‐43 aggregates and axonal transport of TDP‐43 oligomers providing evidence for neuron‐to‐neuron transmission of pathological TDP‐43. We have demonstrated that pathological TDP‐43 extracted from post‐mortem FTLD‐TDP brains, when injected into the brain of doxycycline‐regulatable transgenic mouse models expressing human cytoplasmic TDP‐43 and to a lesser extent in WT mice, led to the formation of de novo TDP‐43 pathology. Interestingly, TDP‐43 pathology progressively spreads throughout the mouse brain in a regional and time‐dependent manner via the neuroanatomic connectome.The distinctive distribution and morphology of TDP‐43 pathology in cortical areas of FTLD‐TDP cases characterize different FTLD‐TDP subtypes, moreover, their different clinical manifestations suggest that distinct pathological TDP‐43 strains could play a role in such heterogeneity. We have recently shown that brain‐derived pathogenic TDP‐43 seeds from different FTLD‐TDP subtypes correlated with distinct biochemical banding patterns of sarkosyl‐insoluble TDP‐43 protein with distinctive seeding properties in vitro and in vivo. Although our experimental animal model does not fully recapitulate the characteristic neuropathological distribution and spreading patterns of TDP‐43 pathology found in the brains of each of the human FTLD‐TDP subtypes, TDP‐43 pathogenic seeds from different FTLD‐TDP subtypes induce distinct morphological types of TDP‐43 and spreading patterns in mouse brains.Our experimental data support the hypothesis that distinct TDP‐43 strains may contribute to phenotypic heterogeneity of TDP‐43 pathology through different mechanisms of disease pathogenicity in TDP‐43 age‐related dementias.
Traumatic Brain Injury and Cognitive Aging Among Older Veteran Men – A Twin Study Accounting for Genetics and Medical Conditions
Authors: Chanti‐Ketterl Marianne 
Published: December 2023

AbstractBackgroundTraumatic brain injury (TBI) is associated with increased risk of dementia, but whether TBI influences cognitive trajectories in later life is less clear. Identifying those at high‐risk of cognitive decline creates intervention opportunities to delay dementia. Since twins share many genes and environmental factors, we capitalize on the twin‐study design to investigate the association between lifetime TBI and cognitive decline.MethodParticipants (n = 8,662) members of the National Academy of Sciences‐National Research Council’s Twins Registry of World‐War‐II Male Veterans born between 1917‐1927 with self or proxy‐reported history of TBI and from one to four assessments over 12 years using the modified‐Telephone Interview for Cognitive Status (TICS‐m). We used linear random‐effects‐mixed models to examine the association between TBI and TICS‐m in the full sample and among co‐twins discordant for TBI. Additional TBI predictor variables included: number and severity (with/without loss‐of‐consciousness[LOC]) of TBI; and age of first TBI (age <25 vs 25+). Models were adjusted for age (centered‐at‐70‐years), age‐squared, education, wave, twin pairs and for lifestyle behaviors and medical conditions. In a subset, we assessed the impact of APOE on TICS‐m.ResultHistory of any TBI, TBI with LOC, and older age of TBI were associated with lower TICS‐m scores at 70‐years (p‐values<0.001). TBI with LOC, more than one TBI, and older age of TBI were associated with faster cognitive decline (p‐values<0.05). Among monozygotic twin pairs discordant for TBI (589 pairs), a history of TBI and having TBI at older age was associated with lower TICS‐m scores (p‐values<0.01); those with more than one TBI and TBI at older age showed greater cognitive decline (p‐values<0.05) compared to their cotwin without TBI. Across all twins, APOE‐e4 carriers with TBI, more than one TBI, TBI with LOC, and older age of TBI had lower TICS‐m scores and greater cognitive decline compared to APOE‐e4 non‐carriers.ConclusionThese findings support an association between TBI and lower cognitive score and more rapid cognitive decline in later life. The results in the monozygotic pairs, who share all genes and many exposures particularly in early life, provide evidence of a causal relationship between TBI and poorer late life cognitive outcomes.
Diagnosis in an early‐onset dementia clinic in the period 2016‐2021 and impact of COVID‐19 pandemic
Authors: Guillén Núria , Contador José , Tort‐Merino Adrià , García Andrea , Martínez Neus Falgàs , Esteller Diana , Sarto Jordi , Castellví Magdalena , Vilas‐Riotorto Vanessa G , Juncà‐Parella Jordi , Borrego‐Écija Sergi , Bosch‐Capdevila Beatriz , González Yolanda , Fernandez‐Villullas Guadalupe , Antonell Anna , Balasa Mircea , Sanchez‐Valle Raquel , Lladó Albert 
Published: December 2023

AbstractBackgroundThe diagnosis of early‐onset neurodegenerative dementias (<65 years) can represent a challenge due to their lower frequency respect to late‐onset dementias and atypical forms of presentation. Cognitive impairment has emerged as a frequent complaint after COVID‐19 infection.MethodWe retrospectively reviewed (2016‐2021) the demographic and clinical data of the new referrals at our early onset dementia clinic (Hospital Clínic Barcelona). We used Fisher’s Exact test and ANOVA in Stata/IC 16.1 to analyze differences between patients visited in 2021, 2020 and the period 2016‐2019.ResultWe evaluated 296 patients in 2021, 104 in 2020 and 98 patients/year in 2016‐2019. In 2021, patients had an age at onset (AAO) of 50.1 years, lower than 2020 (53.4) and the period 2016‐2019 (53.0) (p<0.05). The percentage of women in 2021 (69.6%) was higher than 2020 (57.7) and 2016‐2019 (56.0) (p<0.05). Diagnostic delay was lower in 2021 (2.1 years) than 2020 (3.3) and 2016‐2019 (3.0) (p<0.05). No differences were found in Minimental (MMSE) scores (Table 1).In the period 2016‐2021, the number of neurodegenerative diseases (ND) remained steady, the number of subjective cognitive decline (SCD) decreased and the number of non neurodegenerative causes (NNC) experienced a large increase (Table 1), representing 77.7% of visits in 2021.We did not find differences in the type of ND diagnosis in each period (Figure 1A). ND subgroups did not show differences in AAO, sex or MMSE. In 2021, NND presented lower AAO, higher percentage of women, lower diagnostic delay (Figure 1B) and higher MMSE scores than previous years. No differences were found in the SCD group.Cognitive impairment after Covid‐19 accounted for 16.7% of NND in 2020 (n = 8, AAO 50.6 (11.8), 62.5% female, MMSE 26.8(2.3)) and 66.6% of NND in 2021 (n = 153, AAO 49,0 (10.0), 80.1% female, MMSE 27.8 (2.6)).ConclusionIn 2021 we visited approximately three times more patients than in 2016‐2020, among which we observed an increase in NND, mainly patients with cognitive impairment after Covid‐19. On contrast, we found a similar number of ND diagnosis and reduction in SCD.
Altered Metabolic Connectivity within the Limbic Cortico‐Striato‐Thalamo‐Cortical Circuit in Presymptomatic and Symptomatic Behavioral Variant Frontotemporal Dementia
Authors: Liu Li , Wu Liyong 
Published: December 2023

AbstractBackgroundBehavioral variant frontotemporal dementia (bvFTD) is predominantly considered a dysfunction in cortico‐cortical transmission, with limited direct investigation of cortical‐subcortical transmission. Thus, we aimed to characterize the metabolic connectivity between areas of the limbic cortico‐striato‐thalamic‐cortical (CSTC) circuit in presymptomatic and symptomatic bvFTD patients.MethodThirty‐three bvFTD patients and 33 unrelated healthy controls were recruited for this study. Additionally, six asymptomatic carriers of the MAPT P301L mutation were compared with 12 non‐carriers who were all from the same family of bvFTD. Each participant underwent neuropsychological assessment, genetic testing, and a hybrid PET/MRI scan. Seed‐based metabolic connectivity based on [18F]‐fluorodeoxyglucose PET between the main components within the limbic CSTC circuit was explored according to the Oxford‐GSK‐Imanova Striatal Connectivity Atlas.ResultBvFTD patients exhibited reduced metabolic connectivity between the relays in the limbic CSTC circuit, which included the frontal region (ventromedial prefrontal cortex, orbitofrontal cortex, rectus gyrus, and anterior cingulate cortex), the limbic striatum, and thalamus compared to controls. In the bvFTD patients, the involvement of the limbic CSTC circuit was associated with the severity of behavior disruption, as measured by the frontal behavior inventory, the disinhibition subscale, and the apathy subscale. Notably, asymptomatic MAPT carriers had weakened frontostriatal connectivity but enhanced striatothalamus and thalamofrontal connectivity within the limbic CSTC circuit compared with noncarriers.ConclusionThese findings suggested that aberrant metabolic connectivity within the limbic CSTC circuit is present in symptomatic and even asymptomatic stages of bvFTD. Thus, metabolic connectivity patterns could be used as a potential biomarker to detect the presymptomatic stage and track disease progression.
Montreal Cognitive Assessment MoCA‐XpressO: Validation of a Digital Self‐administered Cognitive Pre‐screening Tool for the General Adult Population
Authors: Klil‐Drori Sivan , Bodenstein Katie C , Kojok Lara , Gruber Johanna , Sun Shuo Mila , Ghantous Youssef , Nasreddine Ziad S 
Published: December 2023

AbstractBackgroundThe population is aging worldwide, and the prevalence of Alzheimer’s dementia is expected to increase, adding demand for cognitive screening. A brief pre‐screening tool may allow self‐tracking of cognitive function and identify the “worried well” population, whom if pre‐screened will show no objective cognitive impairment, consequently reduce demand for cognitive screening. Therefore, we developed the MoCA‐XpressO, a brief home‐based cognitive pre‐screening tool. The purpose of this tool is to establish if further cognitive testing is necessary.MethodWe conducted a validation study for MoCA‐XpressO compared to MoCA test (version 8.1) as gold standard. Participants were recruited from MoCA clinic and a family practice. Ethics approval was received, and all participants provided informed consent. A crossover study design was applied to the MoCA‐XpressO and standard MoCA test; participants were randomized for the order of administration. Inclusion criteria included age ≥50, fluency in English and/or French, and minimum 6 years of education. Exclusion criteria included MoCA total score<11, and completion of MoCA during recent 3 months. Logistic regression model was built, and the accuracy of the model was evaluated by the sensitivity, specificity, and area under the Receiver Operating Characteristic (ROC) curve.ResultThe MoCA‐XpressO evaluates 3 cognitive domains: processing speed, executive functions, and memory. Preliminary analysis (n = 44) showed a strong association between (1) MoCA Memory Index Score (MIS) and MoCA‐XpressO memory task score (p‐values<.001); (2) MoCA Executive Index Score and MoCA‐XpressO logical task score (p‐values<.03); and (3) total scores of MoCA test and MoCA‐XpressO (p‐values<.005). The ROC curve of the logistic model has an Area Under the Curve (AUC) around 0.85. With a cutoff probability of 0.45, the sensitivity was 89.2% and the specificity was 62.5%; with a cutoff probability of 0.6, the sensitivity was 71.4% and specificity was 87.5%. Full analysis (n≥80) will be available in July 2023.ConclusionThe high values of AUC (0.85), indicate that MoCA‐XpressO may be strongly predictive of the standard MoCA. This suggests MoCA‐XpressO is a valid home‐based cognitive pre‐screening tool, also allowing self‐tracking of cognition over time. MoCA‐XpressO may differentiate the “worried‐well” from cognitively impaired population, consequently, reduce the high demand for cognitive screening in healthcare systems.