bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linguistic markers of Alzheimer’s in Spanish speakers: Automated metrics for free speech and verbal fluency tasks
Authors: Garcia Adolfo M 
Published: June 2023

AbstractBackgroundAutomated speech analysis can reveal objective, scalable markers of Alzheimer’s disease (AD). Yet, few studies have targeted Spanish, the most spoken language in Latin America, where AD is quickly escalating. Also, most research presents low interpretability, targeting linguistic features unrelated to the disorder’s core neuropsychological profile. Working with Hispanics, we have validated novel automated metrics capturing critical lexico‐semantic targets for AD: semantic granularity (coarseness of concepts) and ongoing semantic variability (conceptual closeness of successive words) –Figure 1A. I aim to describe and illustrate these metrics via two experiments comparing AD patients and healthy controls (HCs) on free speech and verbal fluency tasks. To test for specificity, replications were conducted in Parkinson’s disease (PD) and behavioral variant frontotemporal dementia cohorts.MethodIn Experiment‐1, 21 AD patients, 16 HCs, and 18 PD patients performed spontaneous and semi‐spontaneous speech tasks. In Experiment‐2, 32 AD patients, 27 HCs, 19 PD patients, and 32 bvFTD patients performed phonological and semantic fluency tasks. In both studies, responses were transcribed and lemmatized. Semantic granularity scores were computed on Python’s NLTK library to access WordNet, a lexical taxonomy leading from hypernyms (top node: ‘entity’) to hyponyms (e.g., ‘dog’). Each word’s granularity is defined as the distance between its node and ‘entity’ (Figure 1B). Ongoing semantic variability was analyzed with a FastText model pre‐trained with Spanish corpora. Each unique word in the vocabulary was assigned a vector, and the distance between words was quantified with the cosine of the angle between their assigned vectors (Figure 1C). Extracted features from both dimensions were analyzed through ANOVAs and XGBoost classifiers.ResultsIn Experiment‐1, relative to HCs, AD (but not PD) patients used more unspecific and fewer specific concepts, alongside more discontinuous conceptual choices. These features robustly classified between AD patients and HCs, but not between PD patients and HCs. In Experiment‐2, only AD patients exhibited reduced semantic granularity, which contributed to robust subject‐level classification. Ongoing semantic variability failed to distinguish among groups.ConclusionThese novel digital metrics can reveal objective, interpretable, and specific markers of AD in Spanish speakers, providing culture‐specific data for a vast but understudied linguistic community.
AT(N) Biomarker profiles and Alzheimer’s Disease clinical status and memory in adults with down syndrome
Authors: Hartley Sigan L , Tudorascu Dana L. , Lee Laise , Petersen Melissa , Cohen Ann D. , Klunk William E , Laymon Charles M , Zaman Shahid , Christian Bradley T. , Handen Benjamin L. 
Published: June 2023

AbstractBackgroundDown syndrome (DS) is seen as a genetic form of Alzheimer’s disease (AD). The National Institute on Aging and the Alzheimer’s Association proposed the AT(N) model for classifying AD biomarkers of amyloid (A), tau (T), and neurodegeneration or neuronal injury ([N]) in non‐DS populations. It is not yet known how the AT(N) classification system maps onto AD pathology and symptomology in DS. The goals of the present study were to: 1) examine AT(N) profiles in DS based on PET amyloid‐beta (Aβ) (A), tau PET (T), and hippocampal volume ([N]); and 2) evaluate potential differences in clinical AD status and memory performance by AT(N) profile in DS.MethodAnalyses included 138 adults with DS (age: M = 39.1, SD = 8.0) enrolled in the Alzheimer’s Biomarker Consortium‐ Down Syndrome study. PET Aβ and tau were assessed using [11C]PiB and [18F]AV‐1451. Structural MRI data was used to index hippocampal volume and adjusted for intracranial volume. Thresholds for elevated (+ vs. ‐) A (Aβ CL >19), T (tau composite SUVr >1.21) and (N) (hippocampal volume < 1 SD from sample mean) were based on prior studies. Clinical AD status (cognitively stable, mild cognitive impairment [MCI‐DS], dementia, and unable to determine) were based on direct measures and caregiver‐report but blind to imaging and biofluid data. The Cued Recall Test was used to assess episodic memory.ResultOverall, 66% of participants were A‐/T‐/(N)‐, 14% were A+/T‐/(N)‐, 9% were A+/T+/(N)‐, and 5% were A+/T+/(N)+. The remaining 6% had an alternative profile (e.g. A‐/T‐/(N)+). One‐way analyses of variance indicated a significant difference in age and clinical AD status by A/T/N profile. General linear models controlling for age and premorbid intellectual disability level indicated differences in memory by A/T/(N) profile.ConclusionThis study adds to the understanding of AT(N) biomarker profiles in DS and their association with AD symptomology. Clinical AD status of MCI‐DS and dementia and worse memory performance were associated with elevated T and (N), in line with non‐DS populations. The unable to determine status paralleled the MCI and dementia status groups. Findings inform models that predict the transition to AD in DS.aging after age 90.
Development and validation of a dementia risk index for use with administrative healthcare data in Canada
Authors: Chowdhury Mohammad Z I , Seitz Dallas , Jafari Behnaz 
Published: June 2023

AbstractBackgroundIdentification of individuals at high risk for dementia is important for planning health services and targeting prevention strategies. While dementia risk indices are available with clinical data, few have been created for use with population‐based administrative data in Canada. The purpose of this study was to establish a dementia risk index for people aged 50 years and older in Alberta, Canada, utilizing routinely gathered administrative healthcare databases. Using population‐based data, we can better understand the risk of dementia to identify individuals and populations at greatest risk.MethodThe study population included all individuals in Alberta, Canada, aged 50 years or older and free of diagnosed dementia on April 1, 2013. Participants were followed for up to 5 years to assess new diagnoses of dementia using a validated algorithm. A total of 59 known measurable dementia risk factors were assessed as potential predictors of dementia. At a 3:2 ratio, the sample was randomly divided into derivation and validation sets. The risk prediction model was created using a Cox proportional hazard model from a list of candidate variables in the derivation sample, and its performance to predict dementia was evaluated in the validation sample.ResultOne million participants aged 50 years and older without dementia were included in the study sample (mean age 62.95 years, 50.52% female), and 41,834 (3.86%) individuals developed dementia during follow‐up (mean duration 4.78 years). Out of 59 candidate variables, 17 variables were identified as independent risk factors for dementia, including advanced age, female gender, increased overall medical comorbidity, neighborhood measures of socioeconomic deprivation, specific medical conditions, mental health diagnoses, and measures of health service utilization. The final multivariate Cox proportional hazards model demonstrated good discriminative ability (Harrel’s C‐statistic = 0.87).ConclusionThis risk prediction index, derived using population‐based data, can reliably identify Canadian adults at increased risk of dementia. This risk index may assist clinicians, and the general public in assessing their risks for dementia and facilitate discussions on the most effective ways to reduce this risk. Understanding individual or population‐based dementia risk differences can help design dementia prevention and health promotion programs.
Mild behavioral impairment as an indicator of early dementia neurodegeneration: Evidence from structural neuroimaging
Authors: Guan Dylan X. , Rehman Tanaeem , Nathan Santhosh , Durrani Romella , Smith Eric E. , Ismail Zahinoor 
Published: June 2023

AbstractBackgroundMild behavioral impairment (MBI) refers to the de novo emergence of persistent neuropsychiatric symptoms in older adults and has been associated with cognitive decline and incident dementia. The purpose of this study was to identify the structural neural correlates of MBI using a hypothesis‐driven region‐of‐interest (ROI) approach.MethodThe study cohort consisted of 744 participants (60.3% female; mean and SD of age = 71.0 ± 9.7 years; mean and SD of education: 15.8 ± 5.3 years) without dementia from the National Alzheimer’s Coordinating Centre dataset. Structural T1‐weighted images for each participant were processed and segmented using FreeSurfer and then normalized by age, sex, intracranial volume, scanner characteristics, and image quality to generate adjusted measures of grey matter volume (GMV) for each ROI. Our primary ROIs included five regions, each representing one Braak stage: entorhinal cortex (stage I), hippocampus (stage II), fusiform gyrus (stage III), inferior temporal cortex (stage IV), and frontal pole (stage V). We also included three hippocampal subfields (CA1, CA3, CA4) and four ROIs commonly associated with various psychiatric disorders (amygdala, insula, anterior cingulate, prefrontal cortex) as a secondary analysis. All ROIs are anatomically highlighted in Figure 1. Participants were classified as MBI+ if they presented with MBI symptoms derived from the Neuropsychiatric Inventory Questionnaire for two consecutive visits one year apart. Logistic regressions adjusting for cognitive diagnosis (cognitively normal, n = 568; mild cognitive impairment, n = 176) were used to model the relationship between ROI GMV (predictor) and MBI status (outcome).ResultAs shown in Table 1, lower GMV in early Braak stage ROIs (entorhinal cortex and hippocampus) was associated with MBI+ status. This trend was maintained for all hippocampal subfield ROIs. However, mid‐late Braak stage ROI (fusiform gyrus, inferior temporal cortex, frontal pole) GMVs were not associated with MBI status. For psychiatric disorder ROIs, lower GMV in only the amygdala was associated with MBI+ status.ConclusionOur findings demonstrate that the presence of MBI may implicate neurodegeneration in regions linked to early‐stage dementia. Furthermore, this explicitly identifies MBI as a neurodegenerative marker sharing few neuroanatomical correlates with psychiatric disorders, despite their clinical manifestations.aging after age 90.
Alzheimer’s disease and other dementias in China: Secular trend in disease burden from 1990 to 2019 and projections to 2030
Authors: Geng Jiawei , Hesketh Therese 
Published: June 2023

AbstractBackgroundAlzheimer’s disease and other dementias (ADOD) inflict substantial burden on the individual, family and society. China has the world’s highest number of people living with dementia, but the national‐level secular trends have not been well‐characterized.MethodDrawing on data from the Global Burden of Disease Study 2019, we explored the burden of ADOD in China from 1990 to 2019, including its prevalence, incidence, mortality, years of lost (YLLs), years of life lived with disability (YLDs), disability adjusted life years (DALYs), and attributable specific risk factors. Temporal trends in disease burden were calculated by average annual percentage changes (AAPCs) using log‐linear regression in age‐standardized rates. We utilized Bayesian age‐period‐cohort models with integrated nested Laplace approximations to predict the age‐sex‐specific number of new cases and deaths from 2020 to 2030.ResultThe age‐standardized prevalence, incidence, deaths, YLLs, YLDs and DALYs for ADOD were 788.28, 103.83, 23.32, 254.42, 114.07 and 368.49 per 100,000 population in 2019 respectively, with increasing trends observed (AAPC [95% Confidence Interval]: 0.66% [0.57 to 0.75], 0.33% [0.27 to 0.40], 0.15% [0.07 to 0.23], 0.10% [0.01 to 0.20], 0.65% [0.56 to 0.75], and 0.26% [0.21 to 0.31]) during the past three decades. Although ADOD is more prevalent in females, AAPCs in all indicators were more pronounced in males. More dementia cases were attributable to smoking in males than in females. Proportions of DALYs attributable to high BMI increased over time in both sexes, and the cases attributable to high fasting glucose were comparable in both sexes. Incidence and mortality from ADOD are projected to be 2,967,059 and 527,960 cases in 2030, representing a 1.65‐fold increase.ConclusionIncreasing incidence and mortality due to ADOD will continue in coming years due to population aging, although age‐standardized mortality rates showed a slight decrease. Further research on modifiable risk factors and targeted prevention strategies are warranted.
Investigating the Regulatory Role of PKR in Systemic Inflammation Triggered Neuroinflammation and its Role in Cholinergic Neurons in Modulating Cognitive Functions
Authors: Cheng Wai‐Yin , Ho Yuen‐Shan , Chang Raymond Chuen‐Chung 
Published: June 2023

AbstractBackgroundDouble‐stranded RNA‐dependent protein kinase (PKR) is a key signaling molecule that regulates immune responses by regulating macrophage activation, various inflammatory pathways, and the formation of inflammasomes. Meanwhile, PKR in neurons helps mediate stress responses of Aß to trigger apoptosis and affects cognitive functions. This study aims at investigating whether PKR can be a pharmacological target to prevent systemic inflammation‐triggered neuroinflammation and cognitive dysfunctions.MethodThe experimental model of laparotomy is adopted to address the systemic inflammation initiated by surgery. Male C57BL/6J and PKR‐KO mice were divided into two groups: control group under sevoflurane anesthesia and laparotomy group under sevoflurane anesthesia. Cytokine mRNA expression in tissues was examined by quantitative RT‐PCR. Behavioral tests were performed to examine the effects of laparotomy on cognitive functions. Furthermore, to examine the role of PKR in cholinergic neurons, stereotaxic injection of dominant negative AAV‐DIO‐PKR‐K296R into the right lateral ventricle of the Rosa‐ChAT‐IRES‐Cre mice was performed to inhibit PKR in cholinergic neurons.ResultOur preliminary study showed that laparotomy induced systemic and neural inflammation in male C57BL/6J mice. At 4 h and one day after laparotomy, genetic knockout of PKR in mice potently downregulated the elevated IL‐1ß expression generated by laparotomy in both the liver and frontal brain. Additonally, cognitive impairment was observed in wild type mice following laparotomy in terms of the decline in problem‐solving abilities, impaired short‐term and long term memory in the puzzle box test; reduced recognition memory in the novel object recognition test; and impaired spatial working memory in the spontaneous Y‐maze; while for PKR‐KO mice, cognitive flexibility, short‐term and long term memory recognition memory remained intact after laparotomy. Furthermore, at 4 weeks after stereotaxic injection of AAV‐DIO‐PKR‐K296R, a significant reduction of p‐PKR level was observed in cholinergic neurons. It implies that the AAVcan inhibit the phosphorylation of PKR in cholinergic neurons.ConclusionThis study reveals that genetic knockout of PKR in mice could attenuate laparotomy induced systemic inflammation, neuroinflammation, and cognitive impairment.Further studies will be performed to examine the effect of knockout of PKR in cholinergic neurons on cognitive functions.Acknowledgement:The study is supported by General Research Fund (17123217) to RCCC.
Plasma Aβ42/Aβ40 and p‐tau181 are associated with clinical progression in amnestic mild cognitive impairment: An 8‐year longitudinal study
Authors: Xiao Zhenxu , Wu Wanqing , Ma Xiaoxi , Liang Xiaoniu , Zheng Li , Ding Saineng , Lei Qiqi , Chen Ke‐Liang , Zhao Qianhua , Ding Ding 
Published: June 2023

AbstractBackgroundPrevious studies indicated that blood‐based biomarkers could predict cognitive decline in Alzheimer’s disease (AD) continuum.MethodTwo hundred and fifty‐one participants with amnestic mild cognitive impairment (aMCI) from the Shanghai Memory Study were followed up for a maximum of 8 years. Baseline blood biomarkers were measured with the single‐molecule array (Simoa) platform. Multipoint clinical diagnosis and domain‐specific cognitive functions were assessed to investigate the longitudinal relationship between blood biomarkers and clinical AD progression.ResultParticipants with high‐risk plasma Aβ42/Aβ40 (A) and p‐tau181 (T) level demonstrated the highest probability of incident AD (HR 5.54, 95% CI 2.99‐10.27), and the most dramatic decline in global cognition, attention, executive function, visuospatial function, and language. Comparing to young‐old participants, the old‐old ones with low‐ and moderate‐risk AT showed higher AD risks (HR 3.70, 95% CI 1.16‐11.81; HR 3.15, 95% CI 1.37‐7.26), and faster cognitive deterioration.ConclusionThe results supported the use of plasma Aβ42/Aβ40 and p‐tau181 as accessible and feasible indicators of AD progression and the long‐term cognitive deterioration, especially in patients with older age.
Codesign methods when developing a decision guide for eating and drinking problems among hospital patients with severe dementia
Authors: Anantapong Kanthee , Bruun Andrea , Walford Anne , Smith Christina , Manthorpe Jill , Sampson Elizabeth , Davies Nathan 
Published: June 2023

AbstractBackgroundDecisions about eating and drinking for people with severe dementia in acute hospitals are often difficult. Using a codesign process, we developed a decision guide for family carers and hospital professionals to help everyone making these decisions.MethodWe conducted a systematic review and qualitative interviews with people with mild dementia, family carers and hospital professionals in the UK. We ran four online workshops with family carers and hospital professionals to codesign the decision guide. In parallel with the codesign workshops, a matrix approach was used to synthesise data from all studies, including the workshop data, and to develop a prototype of the decision guide. We refined the prototype through workshops and discussions among the research team and lay people. User testing evaluated the prototype, which finalised the decision guide.ResultMost participants were aware of the limited benefits of artificial nutrition and hydration for people with severe dementia. However, participants often found conversations and decision‐making processes confusing and fragmented in hospitals. The codesign process highlighted the importance of meeting individuals’ needs and preferences. The decision guide aimed not only to help people reach evidence‐based decisions but also to support conversations and decision‐making processes. It was designed to clarify the decision‐making process, provide necessary information about eating and drinking interventions, and elicit the values/preferences of everyone involved. It emphasises person‐centred care, best‐interests decision‐making, and multidisciplinary team approaches. From the user‐testing, family carers and hospital professionals perceived the decision guide to be useful in starting conversations and helping with the decision‐making processes. The final version of the decision guide was widely disseminated and is being used in clinical practice.ConclusionThe codesigned decision guide may facilitate conversations between family carers and hospital professionals and help them reach shared decisions that meet the needs and preferences of people with severe dementia. Further evaluation research of the decision guide is required to test its real‐world impacts.
Sex‐specific associations of dietary iron intake with incident dementia: A prospective cohort study
Authors: Pan Wenfei , Chen Hui , Ni Chunxiao , Zhu Jiayi , Zong Geng , Yuan Changzheng , Yang Min 
Published: June 2023

AbstractBackgroundIron has been associated with age‐related cognitive decline and dementia in middle aged and older adults. Nevertheless, as the major source of iron in the body, whether dietary iron intake is related to incident dementia remains poorly understood.MethodA total of 191,694 dementia‐free participants (55.0% female; mean±SD age, 56.2 ± 7.9 years) from the UK Biobank who completed at least one 24h dietary recall at study baseline (2009‐2012) were followed to 2021 (mean = 9.5 years). Dietary iron intake was calculated using the 24h dietary recalls. Incident dementia was identified through hospital admissions and death registries. Cox proportional hazard models were used to assess the overall and sex‐specific associations of dietary iron intake with incident dementia. Participants with iron intake between the 20th and 80th percentiles were considered as reference group.ResultDuring a total of 1,813,480 person‐years, a total of 918 (650 women and 268 men) participants developed dementia. When adjusted for sociodemographic, lifestyle, and other dietary factors, participants in the lowest quintile of iron intake were at significantly higher dementia risk (hazard ratios [HR], 1.40, 95% confidence interval [CI], 1.10‐1.78), while the highest quintile was not significantly related to incident dementia (HR, 1.22, 95% CI, 0.97‐1.55). We detected a significant sex difference in the relations of dietary iron intake to dementia (P‐interaction < 0.001). We observed a U‐shaped association between dietary iron intake and incident dementia in male participants (HRlow, 1.50, 95% CI, 1.09‐2.07; HRhigh, 1.40, 95% CI, 1.03‐1.91; P‐nonlinearity<0.001). Nevertheless, no significant correlation was seen in women, regardless of their menopause status.ConclusionOur study findings suggested a U‐curve relationship between dietary iron intake and risk of dementia among males, which may be related to the differences in direct iron metabolism between the sexes. Further research is warranted to confirm the findings and to investigate the underlying mechanisms of the observed gender differences.