bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical activity reduces the socioeconomic disparity in dementia risk: A UK Biobank cohort study
Authors: Song Suhang , Sun Yitang , Zhang Yuchen , Ye Kaixiong , Shen Ye , Gu Yian 
Published: December 2023

AbstractBackgroundGreater socioeconomic deprivation (SED) has been shown to be associated with a higher risk of dementia. There is an urgent need to investigate whether modifiable lifestyle factors, such as physical activity (PA), can help address the SED disparity in dementia. The current study aims to examine whether PA moderates the association between SED and dementia risk.MethodData were obtained from UK Biobank, a nationwide cohort study with over half a million participants recruited during 2006‐2010. We excluded those diagnosed with dementia at baseline. SED was represented by the Townsend deprivation index (TDI) at recruitment, with a higher TDI score indicating a higher degree of deprivation. PA was assessed by an International Physical Activity Questionnaire, and participants were classified into low, moderate, and high PA groups according to their total amount of PA measured by metabolic equivalents. Dementia was defined from self‐reported verbal interviews, hospital episode records, and death register data. Cox proportional hazard models were used to examine the association of TDI and PA with dementia risk, adjusting for baseline age, sex, ethnicity, self‐reported overall health, and assessment centers.ResultThis study included 399,270 participants (209,358 [52.44%] females, and 363,116 [90.94%] Whites) aged 38‐73 years (mean = 56.32, standard deviation [SD] = 8.12), with a mean follow‐up period of 12.95 years (SD = 1.85). When categorized by TDI tertile, those in the high‐deprivation group (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.24‐1.56, p<0.001) had an elevated risk of dementia, relative to the participants in the low‐deprivation group. Greater PA attenuated the association between TDI and dementia risk (HR[moderate‐PA*TDI] = 0.96, 95% CI = 0.93‐0.99, p = 0.021; HR[high‐PA*TDI] = 0.97, 95% CI = 0.93‐1.00, p = 0.080). In the low PA group, the high TDI group faced 1.46 times (95% CI = 1.13‐1.89, p = 0.004) higher risk of dementia than the low TDI group, while the associations were smaller in moderate (HR = 1.31, 95% CI = 1.10‐1.57, p = 0.003) and high (HR = 1.43, 95% CI = 1.17‐1.74, p<0.001) PA groups.ConclusionGreater PA might, to some extent, help mitigate the detrimental effect of SED disparity in dementia risk, but further research is warranted to explore additional modifiable factors associated with health disparity elimination.
Using plasma ptau181 in Lewy Body Disease spectrum for the identification of Alzheimer’s disease co‐pathology
Authors: Abdelnour Carla , Shahid Marian , Smith Alena , Wilson Edward N. , Vossler Hillary , Plastini Melani J. , Young Christina B. , Winer Joseph R. , Kerchner Geoffrey A. , Andreasson Katrin I. , Henderson Victor , Mormino Elizabeth C. , Poston Kathleen L. 
Published: December 2023

AbstractBackgroundLewy body disease (LBD) patients frequently present with Alzheimer’s disease (AD) co‐pathology, which influences disease progression, cognitive decline, and brain atrophy. AD‐related pathology can be identified with new blood‐based biomarkers like plasma phosphorylated‐tau181 (ptau181).We aimed to determine whether plasma ptau181 helps identify AD‐related co‐pathology in LBD, and whether plasma ptau181 is associated with clinical features, and AD cerebrospinal (CSF) biomarkers.MethodFrom a total of 632 Stanford research participants, we selected 245: 115 cognitively normal (CN), 47 Parkinson’s disease (PD) with normal cognition, 47 on the LBD spectrum (31 MCI and 16 dementia), and 36 on the AD spectrum (14 MCI and 22 dementia). Plasma ptau181 levels were measured with Lumipulse G fully automated platform by Fujirebio with Lumipulse G Assays. A subset of the participants had available AD CSF biomarkers (N = 201) and/or 18F‐Florbetaben PET imaging (N = 73). Diagnostic accuracy was evaluated with area‐under‐the‐curve (AUC) values from receiver‐operating characteristic (ROC) analyses. Linear regression models adjusted for confounding factors were used to analyze effects of baseline plasma ptau181 levels on global cognition (MoCA), global function (CDR‐SOB), motor function (UPDRS Part III), and functional disability (Hoehn and Yahr).ResultPlasma ptau181 levels were higher in the LBD spectrum group compared to CN and PD with normal cognition groups, but lower than in the AD spectrum group.Plasma ptau181 levels predicted CSF ptau181/Aβ42 ratio in LBD spectrum patients with an AUC = 0.87. Including age, sex, years of education, and APOE E4 genotype levels improved the prediction of the model (AUC = 0.94).In the LBD spectrum group, males and females showed similar plasma ptau181 levels, and we found no association between plasma ptau181 levels with age, sex, years of education, MoCA, CDR‐SOB, UPDRS Part III, or Hoehn and Yahr. Nevertheless, plasma ptau181 levels were associated with CSF ptau181 levels and amyloid‐β42/40 after controlling for age and sex.ConclusionPlasma ptau181 levels help identify LBD patients with AD co‐pathology, and are associated with AD CSF biomarkers. These findings support the use of plasma ptau181 as a screening tool for AD co‐pathology in patients with LBD and cognitive impairment.
Sex hormone binding globulin and total testosterone levels are associated with in vivo tau burden differentially between the sexes: findings from the Framingham Study
Authors: Buckley Rachel F. , McGrath Emer R , Scott Matthew R , Coughlan Gillian T , Boyle Rory , Seto Mabel , Ghosh Saptaparni , Jacobs Heidi I.L. , Satizabal Claudia L. , Thibault Emma G. , Vasan Ramachandran S , Murabito Joanne M , Sperling Reisa A. , Johnson Keith A. , Seshadri Sudha , Jasuja Ravi , Bhasin Shalender , Beiser Alexa S. 
Published: December 2023

AbstractBackgroundIn men and women, sex steroid hormones are associated with increased risk of Alzheimer’s disease (AD) dementia. In older men, lower levels of testosterone are associated with higher rates of AD dementia. The relationship between estradiol levels on AD dementia risk in post‐menopausal women, however, is less clear, with studies reporting protective, deleterious and no effects. Finally, higher levels of sex hormone binding globulin (SHBG), a glycoprotein that regulates, and actively influences sex hormones, has been consistently linked with increased risk for AD dementia. Studies have yet to examine mid‐life hormonal levels in association with later‐life in vivo AD biomarkers in cognitively healthy adults.Method175 women and 159 men from the Framingham Study 3rd Generation cohort underwent blood (hormones) collection in 2002‐2005, and 18F‐Flortaucipir (FTP)‐PET and 11C‐PiB‐PET scans in 2016‐2020 (Table1). We examined FTP‐PET signal (referenced to cerebellar grey) in six a priori regions that previously demonstrated sex differences (entorhinal, inferior temporal, rostral middle frontal, inf/sup parietal and lateral occipital). Linear regressions examined sex‐stratified analyses of free/total testosterone, estradiol, and SHBG in each region, adjusting for age, age2, PET camera and plasma‐PET date‐difference (mean = 15(±2)yrs). Separate models examined interactions with a neocortical PiB‐PET composite and APOEε4.ResultIn men, elevated SHBG was associated with lower FTP‐PET in entorhinal (p = 0.007), inferior temporal (p = 0.04) and rostral middle frontal regions (p = 0.02; Table2). Higher total testosterone was marginally associated with lower FTP‐PET signal in the latter region (p = 0.06), but other relationships were apparent. In women, higher total testosterone associated with lower FTP‐PET signal in inferior temporal (p = 0.05) and parietal regions (p = 0.04). Women APOEε4 carriers with higher estradiol showed higher levels of entorhinal FTP‐PET signal (p = 0.03;Table3).ConclusionHigher levels of SHBG are associated with lower risk of AD‐related comorbidities, such as osteoporosis, diabetes, and visceral weight gain. A strong link between higher SHBG levels and higher HDL‐cholesterol may suggest a potential protective cardiovascular pathway for men against higher tau burden later in life. A lack of protective effect of pre‐menopausal estradiol in female APOEε4 carriers supports the notion that the role of estrogen in AD risk is centered around timing of decline.
Impact of COVID‐19 infection on the cognition and emotion of Peruvians: analysis after 6‐12 months post‐infection
Authors: Zegarra‐Valdivia Jonathan Adrian , Arana‐Nombera Harold Alessandro , Perez‐Fernandez Leandro Aron , Matallana‐Sanchez Maribel Jesus , Alamo‐Medina Reyna Elizabeth , Rocio Casimiro‐Arana Milagros , Bustamante‐Delgado Diana Lisseth , Gallegos‐Manayay Viviana Nayelli , Álvarez‐Bravo Elizabeth Killasumac , Arteaga‐Cancino Tihany Liliana , Abanto‐Saldaña Eduardo Sebastián , Rosario Oliva‐Piscoya María , Ordinola Maria Celinda Cruz , Chavarry Patricia , Chino‐Vilca Brenda Nadia ,   Group of Neuroscience and Mental Health, Universidad Señor de Sipán, Chiclayo, Perú
Published: December 2023

AbstractBackgroundCOVID‐19 pandemic significantly impacted different systems and organs (cardiovascular, metabolic, immune, brain, and others). More than two years after the first wave of COVID‐19 in Peru, we still do not know the consequences on cognition and emotion, and nowadays, different studies suggest the impact of COVID‐19 might trigger mild cognitive impairment, dementia, and neuropsychiatric syndromes in the future.MethodsAn ex‐post facto study was carried out with two groups, considering a neurocognitive evaluation (general cognition, verbal fluency, attention, and executive function) and emotion (depression, anxiety, and stress) and performed between 6 and 18 months after the first confirmed diagnosis of COVID‐19 in Peruvians (by PCR or antigen test). The mean age was 37.03 ± 15.57 (age range between 17 and 86 years old), and 60.5% were Female. We use the following instruments: INECO Frontal screening, Addenbrooke’s Cognitive Examination‐Revisado (ACE‐R), Verbal Fluency, TMT A/B, and DASS‐21.ResultsNo specific differences in general cognition were found. However, we found an effect in the INECO Frontal Screening (IFS) and the DASS‐21 (Anxiety scale). Patients diagnosed with COVID‐19 by PCR or antigen test have a slightly reduced frontal function (executive function).ConclusionsCOVID‐19 impacted high hierarchical frontal functions, but these effects are not well identified with general cognitive testing. Similarly, an increase in anxiety was found. More specific evaluation and sensitive techniques are needed to elucidate future COVID‐19 consequences on brain function.
Frailty and behavioral and psychological symptoms of dementia: a single center study
Authors: Calsolaro Valeria , Rogani Sara , Coppini Giulia , Lemmi Bianca , Taverni Irene , Bianchi Elena , Pullia Rosanna , Carlo Ludovica Di , Okoye Chukwuma , Virdis Agostino , Monzani Fabio 
Published: December 2023

AbstractBackgrounddementia is a clinical syndrome characterized by progressive cognitive decline and loss of independence in activities of daily living. Alongside the cognitive symptoms, Behavioral and Psychological Symptoms of Dementia (BPSD) may arise, causing considerable distress to both patients and caregiversMethodaim of this retrospective study was to evaluate the correlation between frailty and BPSD in a population of older patients with dementia. BPSD were classified in three clusters: “mood/apathy”, “psychosis” and “hyperactivity”. Using the Clinical Frailty Scale (CFS), patients were categorized as “severely frail”, “mild/moderately frail” and “robust” (CFS ≥ 7, 4‐6 and ≤ 3, respectively). In order to better understand the complex pattern of relationships between the different factors, we performed a network analysis.Result209 patients (71.3% women, mean age 83.24±4.98 years) with a clinical diagnosis of dementia were enrolled. The most represented group was the mild/moderately frail one (n = 155, 74%); lower numbers were seen in the robust (n = 18, 9%) and severely frail (n = 36, 17%) ones. Among the “severely frail” the percentage of BPSD was higher compared to the “mild/moderate” and “robust” groups. A significant correlation between frailty and “hyperactivity” cluster emerged, both at baseline and follow up visits (p<0.001, p = 0.022, p = 0.028 respectively). At the network analysis, the degree of frailty related to behavioral and psychological symptoms of the hyperactivity cluster, such as agitation and motor aberrant activity; the relationship was still positive although not so strong with other symptoms like apathy and hallucinations.Conclusionin this study an association between frailty and the number of neuropsychiatric symptoms of the “hyperactivity” cluster was found; however, whether the loss of independence is a possible cause of frailty or viceversa is still to be determined. The assessment of frailty may help identifying patients at risk of developing behavioral and psychological symptoms of dementia, and could provide the clinicians with a time‐window to target intervention in the earliest phases of both frail condition and BPSD.
Effect of Age Range on Power for a Clinical Trial Investigating the Effect of Intensive Systolic Blood Pressure Control on White Matter Hyperintensity Volume Accumulation
Authors: Pruzin Jeremy J. , Chen Yinghua , Chen Kewei , Koijs Daniel , Newby Danielle , Winchester Laura M , Thomas Ronald G. , McGrath Emer R , Su Yi , Reboussin David M. , Pajewski Nicholas M. , Beiser Alexa S. , Seshadri Sudha , Tariot Pierre N. 
Published: December 2023

AbstractBackgroundEpidemiological evidence has repeatedly demonstrated elevated systolic blood pressure (SBP) in midlife as a modifiable risk factor for Alzheimer’s Disease and Related Dementia (ADRD) later in life. Despite SBP being readily treatable with safe and inexpensive medications, no clinical intervention implementing a lower SBP goal (<120 mm Hg) in midlife to lower future ADRD risk has ever been attempted. Clinical outcomes are not practical in the age range of interest (45‐65 or 45‐70) during an initial trial period of 5 years however robust evidence demonstrates white matter hyperintensity volume (WMHV) as an MRI finding associated with and predictive of incident ADRD.MethodWe used four data sets (SPRINT, Wisconsin Registry for Alzheimer’s Prevention, Framingham, and UK Biobank) with longitudinal MRI data to examine the effect of age range on power for a clinical trial proposal investigating the effect of intensive SBP control on annualized rates of WMHV accumulation in persons starting in middle age. Analyses were conducted separately in each data set. We calculated mean, standard deviations, and annualized rates of WMHV accumulation (derived from T2 FLAIR MRI), using the linear rate of change for accumulation rate, first stratifying by SBP (≥132 mm Hg vs <132mm Hg except in SPRINT where groups were stratified by goal SBP group) and then by various age ranges. Next, we examined the effect of age range on necessary sample size with 80% power and two‐tailed alpha of 0.05 for a prospective clinical trial.ResultAs expected, annualized WMHV accumulation rate is lower with younger age in all data sets. However, variability decreased (all four data sets) and the percent reduction achieved at lower SBPs is higher at younger ages (3/4 data sets), thus increasing power when excluding older individuals (e.g., >65 years old, Table 1).ConclusionRestricting age to individuals to ≤65 years‐old may unexpectedly increase power in a clinical trial designed to investigate the effect of goal SBP<120 mm Hg on annualized WMHV accumulation rate. 45‐65 years‐old is a practical age range for the first ever clinical trial intended to investigate the effects of a lower SBP goal in middle age to reduce future ADRD risk.
Optimising speech‐testing to predict prodromal Alzheimer’s disease: head‐to‐head comparison study of tasks and analysis methods
Authors: Meepegama Udeepa , Skirrow Caroline , Weston Jack , Ropacki Michael T. , Fristed Emil 
Published: December 2023

AbstractBackgroundChanges in speech occur in early‐stage Alzheimer’s disease. A range of approaches have been used for eliciting and automatically analysing speech, but limited research has directly compared these methods.MethodParticipants from the AMYPRED‐UK (NCT04828122) and AMYPRED‐US (NCT04928976) studies completed four speech‐elicitation tasks: the Automatic Story Recall Task (ASRT), the Logical Memory Test (LMT), Semantic (Animals, Vegetables, Fruit) and Phonemic Verbal Fluency (F, A, S) Tasks. Responses were recorded and automatically transcribed. Analyses were completed with Novoic’s speech analysis software, using four key approaches: (1) feature extraction, (2) representations from large language models (LLM), (3) text‐similarity evaluation, and (4) autoscoring. Together, these evaluated audio, linguistic, and temporal speech domains. Outputs were entered into logistic regression models predicting Mild Cognitive Impairment (MCI)/mild AD and Amyloid positivity in MCI/mild AD. Area under the ROC curves (AUC) were evaluated via 5‐fold cross‐validation.Result165 older adults (including N = 74 MCI and 9 mild AD; of which N = 38 MCI/mild AD and amyloid beta positive) provided data for all tasks. Strength of model predictions varied by task, analytic approach and domain (Fig 1). AUCs predicting MCI/mild AD were generally higher for ASRTs compared to other tasks (Fig 1A). Text‐similarity approaches (G‐match: similarity of word embeddings between the source text and retelling, and V‐match: string‐based matching), produced the highest AUC for ASRTs (G‐match AUC = 0.87‐0.88), and the LMT (V‐match AUC = 0.83‐85). Autoscoring tasks produced the strongest predictor for the semantic fluency (AUC = 0.85), and also one of the strongest for phonemic fluency (AUC = 0.72). Changes in linguistic and temporal characteristics were more sensitive to MCI/mild AD, compared to audio‐only metrics. Amyloid in MCI/mild AD predictions were overall less strong (Fig 1B), with the most consistent pattern being better performance of text‐similarity approaches on story recall tasks (up to AUC = 0.77 for ASRTs, 0.73 for LMT).ConclusionSelection of task and analytic approach is important for developing more sensitive speech‐based testing. The best performing tasks (ASRT, Semantic Fluency) and metrics (text‐similarity metrics and autoscoring) have been incorporated in Novoic’s Storyteller automated remote speech‐based test.
Gait and balance measures and tools for early detection of dementias: A systematic review
Authors: Cepukaityte Giedre , Newton Coco , Chan Dennis 
Published: December 2023

AbstractBackgroundBrain mechanisms supporting gait and balance are vulnerable to early neurodegenerative changes and identification of alterations in these behaviours has great potential for the detection of different dementia‐causing diseases. This systematic review aimed to identify the most promising gait and balance measures for early detection and technologies suitable for capturing these data and future deployment at scale in clinical practice.MethodWe performed literature searches following PRISMA guidelines across two databases (PubMed and Web of Science). Keywords were designed to capture literature on preclinical and prodromal stages of dementias and high‐risk populations that investigated gait and balance cross‐sectionally and longitudinally. We included studies written in English and published until August 2022. Exclusion criteria included case, intervention, and uncontrolled studies. Studies on established dementia were also excluded.ResultFrom 2086 titles, 182 were screened at full‐text stage, with 95 included in the systematic review. Most investigated gait and balance in association with preclinical or prodromal AD [n = 38], Parkinson’s [n = 18] or Lewy body [n = 17] dementias, with very few on FTD [n = 1] or vascular cognitive impairment [n = 2]. Twenty‐two studies utilised a term “dementia”. Fifty‐one unique metrics were used to characterise gait, with 12 balance metrics identified. The most common differentiative metric was gait speed (n = 44 studies), which declined across populations, and was often measured using a stopwatch. Twenty‐seven studies utilised pressure carpets, force platforms and body‐worn sensors, enabling quantification of finer‐grained metrics of gait and balance, e.g., variability, asymmetry, and movement jerkiness. These metrics were shown to be sensitive, especially under dual‐task conditions, and specific to different pre‐dementia states. Only three studies utilised smartphone‐based assessment, potentially the most scalable platform for at‐scale application.ConclusionGait and balance measures can detect early neurodegenerative diseases but measurement using scalable off‐the‐shelf technologies in real‐world settings is currently limited. These findings will guide the selection of gait‐measuring devices for the next generation EDoN (https://edon‐initiative.org) toolkit for early detection.
Retinal Manifestations of Alzheimer’s Disease: MicroRNAs and Microglial Phenotypes
Authors: Matsubara Joanne A , Wijesinghe Printha , Irani Lyden , Nassrallah Wissam , Li Charles , Yin Phoenix , Bhandol Harjot , Xu Qinyuan (Alis) , Campbell Matthew , To Eleanor , Xi Jeanne , Cui Jing , Pham Wellington , Lee Sieun 
Published: December 2023

AbstractBackgroundAs part of the CNS, retina is a promising site for studying Alzheimer’s disease (AD) and developing potential biomarkers for accessible screening and early diagnosis. Our group has previously investigated retinal amyloid beta (Aβ) deposition, glial cell degeneration, drusen aggregation, microRNA (miRNA) analysis in AD mouse models, and in vivo fluorescence in the retinas from AD donor eyes and AD animal models. We report on our updated work on miRNA expression in mouse models and microglia morphology in the human AD retina.MethodTen candidate miRNAs were investigated in the brain and eye tissues and tear fluids of transgenic APP‐PS1 mice, non‐carrier siblings, and wildtype (WT, C57BL/6J) controls at young (∼3months) and old (∼10months) ages. 3D microglia morphology was quantitatively and qualitatively analysed in Z‐stacks of human donor retinal tissues stained for microglia (IBA1), activated microglia (CD68) and retinal vessels (UEA‐lectin).ResultRelative miRNA expression levels were similar in APP‐PS1 mice and non‐carrier siblings compared with WT, suggesting the miRNAs were mostly intergenic. Relative miRNA expression was lower in neocortex‐hippocampus, eye tissues, and tear fluids compared to other regions in young transgenic mice, but the same regions showed higher relative miRNA expression in old transgenic mice. miRNAs associated with Aβ misfolding (miRNA‐101a, ‐15a and ‐342) and proinflammation (miRNA‐125b, ‐146a, and ‐34a) showed significant upregulation in tear fluids with disease progression tracked by cortical Aβ load and reactive astrogliosis. Custom software analysis suggest distinct populations of microglia in the AD retina vs. age‐matched control human retina based on 1) morphology (e.g., ramified to amoeboid), 2) their activation state and 3) retinal vessel proximity.ConclusionOur results demonstrate the non‐invasive potential for analysis of miRNAs from tear fluids and the in vivo imaging of the retinal microglial for tracking AD progression.