bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma biomarkers of Alzheimer’s disease in dementia with Lewy bodies
Authors: Bolsewig Katharina , Gonzalez Maria Camila , Ashton Nicholas J. , van Unnik Annemartijn A. J. M. , Blujdea Elena R. , Aarsland Dag , Zetterberg Henrik , Padovani Alessandro , Bonanni Laura , Mollenhauer Brit , Schade Sebastian , Vandenberghe Rik , Poesen Koen , Kramberger Milica G. , Paquet Claire , Bousiges Olivier , Cretin Benjamin , Willemse Eline A.J. , Teunissen Charlotte E. , Lemstra Afina W. ,   European‐Dementia with Lewy Bodies (E‐DLB) Consortium
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) co‐pathology is a common feature in dementia with Lewy bodies (DLB) and associated with a more rapid decline. Here, we aimed to evaluate plasma biomarkers as alternatives for CSF biomarkers for the detection of amyloid pathology, and for their diagnostic and prognostic value in DLB.MethodPlasma Aβ42/40, GFAP, NfL, pTau181 and pTau231, were measured by SIMOA in patients with DLB (n = 342), AD (n = 131), and healthy controls (n = 89) from the E‐DLB consortium cohort. Associations of biomarkers with CSF Aβ42 status were assessed with ANCOVA corrected for age and sex. ROC analyses were performed to assess biomarker’s performance for amyloid detection and differential diagnosis. Associations of biomarkers with cognitive impairment and decline were determined by linear regression and mixed effects models.ResultAltered Aβ42/40 (β = ‐0.0076, 95%CI:‐0.0137 to ‐0.0016, p<.05), pTau181 (β = 0.2503, 95%CI: 0.0555 to 0.4451, p<.05) and pTau231 levels (β = 0.2269, 95%CI:0.0347 to 0.4191, p<.05) were associated with amyloid pathology in DLB, as assessed by CSF Aβ42. The combination of these biomarkers differentiated amyloid normal from abnormal DLB patients with an AUC of 0.728 (sensitivity = 64.6%, specificity = 75.0%). pTau181 best differentiated these groups as a single marker (AUC = 0.700, sensitivity = 62.5%, specificity = 73.1%). The combination of Aβ42/40, NfL and pTau231 differentiated DLB from AD with an AUC of 0.726 (sensitivity = 73.3%, specificity = 68.8%). In DLB, increased GFAP (β = ‐8.9, 95%CI:‐11.7 to ‐6.1, p<.001), NfL (β = ‐7.2, 95%CI:‐10.0 to ‐4.4, p<.001), pTau181 (β = ‐2.6, 95%CI:‐4.0 to ‐1.2, p<.001) and pTau231 (β = ‐2.4, 95%CI:‐3.7 to ‐1.2, p<.001) were associated with lower baseline MMSE scores and increased GFAP (annual change of ‐2.1 MMSE points (95%CI:‐2.9 to ‐1.3, p<.001) and NfL (annual change of ‐2.1 MMSE points (95%CI:‐3.0 to ‐1.3, p<.001) predicted faster cognitive decline.ConclusionPlasma Aβ42/40, pTau181 and pTau231 were associated with amyloid abnormality in DLB. Their utility for differential diagnosis and identifying amyloid pathology in DLB was modest. Our findings suggest a prognostic value of GFAP and NfL for cognitive decline in DLB.
What does ‘super‐ageing’ mean to high‐functioning Australian older adults?
Authors: Powell Alice , Page Zara A , Close Jacqueline CT , Sachdev Perminder S. , Brodaty Henry 
Published: December 2023

AbstractBackground‘Super‐ageing’ has been used to refer to older adults who maintain high level cognitive abilities into advanced age. However, there is no universally accepted definition of this phenomenon and it is unclear what older adults think of the term, how it is defined and what benefits studying such individuals may bring.MethodInterviews and focus groups were conducted using a combination of in‐person meetings and online video conferencing with 8 overtly high‐functioning older community members aged between 81 and 101 living in Australia. Interviews were transcribed and thematically analysed.ResultKey themes were independence, having enough cognitive ability to ‘manage yourself’ and ‘do all the things you want to do’ (such things would be different for each individual), contributing meaningfully to society and remaining engaged particularly with younger members of the community. For this group, it was important to not be physically incapacitated or in chronic pain but physical challenges could be coped with if cognition was intact. Longevity in itself was not important. Some elders emphasised broader concepts of valuing older individuals in society, the necessity of individuals and societies to prepare for the challenges of ageing and the notion of being a role model to younger adults.ConclusionSuper‐ageing is a highly individual construct to this small sample of high‐functioning older adults. Functional independence is central but lacking in most research definitions. Some elements that are very important for these older people, such as living a meaningful life or being socially engaged, have not been considered in existing definitions.
Impacts of depression, apathy, and anxiety on cognitive function in older adults with subjective cognitive decline
Authors: Makino Taeko , Umegaki Hiroyuki , Kuzuya Masafumi , Taki Yasuyuki 
Published: December 2023

AbstractBackgroundAlthough previous studies showed that neuropsychiatric symptoms are associated with cognitive decline, the results are controversial. We investigated the impacts of depression, apathy, and anxiety on cognitive function in older adults with subjective cognitive decline (SCD).MethodAltogether, 464 subjects aged 65‐85 years who had SCD were enrolled in this study. All participants were evaluated with the short version of Geriatric Depression Scale (GDS15), Starkstein’s Apathy Scale (AS), the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), and 9 cognitive tasks assessed using the Mini‐Mental State Examination, Logical Memory and Visual Reproduction subtests of the Wechsler Memory Scale‐Revised, Verbal Fluency Test, Digit Span, Visual Memory Span and Digit‐Symbol subtests of the Wechsler Adult Intelligence Scale‐III, Stroop Test, and Trail Making Test. We performed a Pearson correlation analysis to examine the associations between depression, apathy, and anxiety, and a multiple linear regression analysis, adjusted for age, sex, educational level, and global cognitive state to determine the impacts of depression, apathy, and anxiety on cognitive function.ResultPearson correlation analysis revealed a low‐ to moderate‐grade relationship among depression, apathy, and anxiety, as shown by the correlation between GDS15 and AS (r = 0.49, p < 0.01), GDS15 and HADS (r = 0.36, p < 0.01), and AS and HADS (r = 0.18, p < 0.01). The multiple linear regression analysis, with each cognitive task score as dependent variable, indicated a significant association of the HADS with lower scores on Logical Memory I (beta = −0.18, p < 0.001) and II (beta = −0.14, p = 0.002), after adjusting for the subjects’ age, sex, educational level, and global cognitive state.ConclusionOur results suggest that anxiety may be associated with immediate and delayed memory functions in older adults with SCD.
Feasibility of ADappt: towards personalized communication and prediction in early Alzheimer’s disease in memory clinics
Authors: Hendriksen Heleen M.A. , de Rijke Tanja J. , van Gils Aniek M. , de Beer Marlijn , Bouwman Femke H. , Hempenius Liesbeth , van Maurik Ingrid S. , Pel‐Littel Ruth , Meester Hanneke F.M. Rhodius‐ , Roks Gerwin , Smets Ellen M.A. , van der Flier Wiesje M. , Visser Leonie N.C. 
Published: December 2023

AbstractBackgroundADappt is a Web‐based toolkit (www.ADappt.health) to support personalized communication and prediction in memory clinics. In the context of an iterative development process with professionals, patients, and care partners, we assessed feasibility, satisfaction, and usability of ADappt in the clinical workflow.MethodWe conducted a feasibility pilot in four Dutch memory clinics. Three neurologists, one geriatrician, two specialized nurses and two medical doctors (12±7y clinical experience) participated and recruited 21 patients (69±8yrs, 19%F) and 21 care partners (60±15yrs, 81%F). For professionals, ADappt‐modules comprised a 1) topic list, 2) shared decision‐making conversation guide, 3) overview of diagnostic tests, and 4) risk calculation tool. Prior to their visit, patients and care partners were informed about ADappt‐patient tools: 1) educational video‐animations, and 2) question prompt list. All participants completed questionnaires on feasibility, satisfaction, and usability after the first (n = 17) and/or the disclosure (n = 7) consultation. Professionals were interviewed afterward.ResultProfessionals reported good usability (68±14, range 50‐83, System Usability Scale, 0‐100) and high satisfaction (71±10, range 50‐85, scale 0‐100). They most often used the overview of diagnostic tests (67%) and reported this module as most helpful (3.8±0.4, range 3‐4, scale 1‐5). Patients and care partners were highly satisfied with the clinician‐patient consultations in general (81±14, range 50‐100, Patient Satisfaction Questionnaire, scale 0‐100). Of those who reported to know and have used the patient tools (54%), 97% would recommend them, whereby most used the question prompt list (84%) and a smaller proportion the video‐animations (64%). Recommendations from the interviews to improve feasibility include: 1) the development of more concrete instructions for professionals on how to use ADappt, and 2) a better alignment of patient tools with the patient journey and general information provided by that particular memory clinic.ConclusionStakeholders reported good usability and high satisfaction regarding ADappt. Points of attention to foster feasibility in the clinical workflow are: 1) improved training for professionals and 2) improving the accessibility of patient tools. We take these matters into account while preparing for the next step: a prospective validation study in the memory clinic setting to study the influence of ADappt on patient satisfaction.
Attention‐deficit/hyperactivity disorder in old age and the risk of dementia: A national cohort study in Israel
Authors: Levine Stephen Z , Rotstein Anat , Beeri Michal S , Weinstein Galit , Reichenberg Abraham , Sandin Sven , Kodesh Arad 
Published: December 2023

AbstractBackgroundEvidence of the association between Attention‐Deficit/Hyperactivity Disorder (ADHD) and the risk of dementia is scarce, inconsistent, and subject to potential sources of bias that are as yet unconsidered. Our objective was to examine the association between ADHD and dementia risk.MethodA prospective national cohort study born 1933‐1952, without a dementia diagnosis for two years, were followed up for incident dementia from 2002‐2020. Information was from electronic health records in a healthcare maintenance organization in Israel. ADHD diagnosis was classified as present from the age of the first diagnosis, otherwise absent. Competing risk Cox regression models were fit to quantify the risk of incident dementia with the Hazard Ratio (HR) and their associated 95% Confidence Intervals (CI) with inverse probability weights, age as the underlying time‐scale, unadjusted and, in the primary analysis, adjusted by 18 covariates.ResultOf 110,196 participants aged 50‐70 years in 2002, 56,914 (51.6%) were female. During follow‐up there were a total of 746 (0.7%) cases of ADHD, and 8,339 (7.6%) of incident dementia. The percentage of incident dementia was 13.1% (N = 98) among those with ADHD present and 7.5% (N = 8,241) among those with ADHD absent. In the primary analysis, the group with ADHD was statistically significantly (P<.05) associated with a higher risk of dementia (unadjusted: HR = 3.57, CI = 2.89, 4.42; adjusted HR = 2.73, CI = 2.04, 3.65) compared to the group with ADHD absent. Eight of ten sensitivity analyses replicated the statistically significant association observed in the primary analysis. Psychostimulant medication offset the association between ADHD and dementia risk to null, and evidence of reverse causation was mild.ConclusionADHD is associated with increased dementia risk. Policymakers, caregivers, patients, and clinicians may wish to monitor ADHD in old age reliably.
Differential gene expression analysis in individuals with depression in Alzheimer’s disease using RNAseq
Authors: Sinclair Lindsey I , Ballard Clive G , Bennett David A. A 
Published: December 2023

AbstractBackgroundDepression in individuals with Alzheimer’s disease (AD) is common, distressing, difficult to treat, may increase carer burden and is inadequately understood. It occurs more frequently in AD than in older adults without dementia. The underlying biology remains obscure.We aimed to identify patterns of differential gene expression in individuals with depression in AD compared to individuals with AD but no history of depressive illness.MethodWe used data from the Religious Orders Study and the Memory and Aging Project: the ROSMAP cohort. Individuals with other disorders which could have caused cognitive impairment e.g. Parkinson’s disease(n = 122) or clinically significant head trauma (n = 234) were excluded, and those with bipolar disorder(n = 13). Those with neuropathological or consensus clinical evidence of a dementia other than Alzheimer’s disease were also excluded (n = 116).Depression caseness was defined as a highly probable/probable clinical diagnosis of depression made by the assessing clinician at a study visit or a CESD score of >7 at a study visit. Individuals with treated depression (n = 301) who were taking antidepressants but never met depression caseness criteria and 380 individuals with subthreshold depressive symptoms on the CESD but a clinical assessment that depression was “not present” were also excluded.RNAseq data was available from the DLPFC and posterior cingulate. The posterior cingulate analysis is ongoing. Fastq files were quality controlled using fastqc and Picard following HISAT2 alignment to GRCh38. After exclusion of files which failed QC fastq files were aligned to the GRCh38 transcriptome using Salmon. Files with low transcriptome alignment (<28%) were also excluded. Differential gene expression analysis was carried out in Rstudio using DEseq2.ResultAfter exclusions and QC, data was available for 15 individuals with depression & AD and 25 individuals with AD but no depression for the DLPFC. Age, RIN, sex and Braak stage were included in the analysis model. After adjustment of the p value for multiple comparison 64 genes were differentially expressed in depression including Fbox proteins, nucleosome assembly proteins and voltage‐gated channel proteins. KEGG pathway analysis is underwayConclusionWe have identified genes differentially expressed in depression in AD which may allow better understanding of this condition.
Sex‐dependent effects on the association between air pollution and longitudinal changes in CSF and plasma biomarkers of Alzheimer’s disease
Authors: Vilor‐Tejedor Natalia , Escalante Armand González , Rodríguez‐Fernández Blanca , Genius Patricia , Milà‐Alomà Marta , Ortiz‐Romero Paula , Cirach Marta , Nieuwenhuijsen Mark , Sunyer Jordi , Minguillon Carolina , Fauria Karine , Kollmorgen Gwendlyn , Carboni Margherita , Molinuevo Jose Luis , Navarro Arcadi , Zetterberg Henrik , Blennow Kaj , Suarez‐Calvet Marc , Gispert Juan Domingo 
Published: December 2023

AbstractBackgroundA growing body of research links environmental factors with neurodegeneration and premature mortality. However, the biological mechanisms through which the different pollutants may be affecting Alzheimer’s disease (AD) pathology in the early asymptomatic stages of AD and the downstream consequences are unknown. We aimed to evaluate the association between air pollution and longitudinal change rates of cerebrospinal fluid (CSF) and plasma biomarkers of AD in cognitively unimpaired individuals.MethodThe study included 195 middle‐aged cognitively unimpaired participants from the ALFA+ study, many within the Alzheimer’s continuum, with baseline and one follow‐up measurement of biomarkers of primary pathology of AD such as cerebrospinal fluid (CSF) β‐amyloid (Aβ) Aβ42/40 ratio (exploratory Roche NeuroToolKit assays [Roche Diagnostics International Ltd, Rotkreux, Switzerland]), plasma Aβ42/40 (Quanterix Simoa Neurology 4‐Plex E Advantage Kit), and CSF phosphorylated tau181 (p‐tau181) (Roche Elecsys® Phospho‐Tau [181P] CSF assay). Land use regression models were used to estimate individual levels of air pollution, including nitrogen oxide (NO2) and particulate matter (PM2.5, PM10), at the participants’ residential area. General linear models corrected by age, sex, APOE‐ε4 status, and time between measurements were conducted to assess the association between environmental exposures and biomarker changes. Sex‐specific effects were also investigated by including an interaction term.ResultHigher levels of exposure to PM2.5 were significantly associated with greater longitudinal reduction in plasma Aβ42/40 (β = ‐0.188, padjusted = 0.024). In addition, significant interactions between sex and NO2 (padj = 0.016), PM2.5 (padjusted = 0.008), and PM10 (padjusted = 0.007) on longitudinal change rates of plasma Aβ42/40 were found. Results showed that as the level of exposure increased, men presented reductions in plasma Aβ42/40 levels while women did not show significant changes (Figure 1). No significant results were found for longitudinal change rates of CSF biomarkers.ConclusionThese results reinforce the role of air pollution as a sex‐dependent environmental risk factor for AD pathology in asymptomatic individuals. Although more research is needed to elucidate the mechanisms involved in these associations, our results may inform better personalized prediction and prevention practices.
Can the proposed research criteria for prodromal behavioural variant FTD be a bridge between neurologists and psychiatrists for early diagnosis?
Authors: El‐Jaafary Shaimaa Ibrahim , Ortuño Roman Romero 
Published: December 2023

AbstractBackgroundThe early diagnosis of the behavioural variant of frontotemporal dementia (FTD) is very challenging to clinicians. This type of dementia has a wide range of clinical variability, and the psychiatric presentation adds to the complexity of the differential diagnosis. The need for early precise diagnosis of FTD in the prodromal phase is increasing for tailored interventional strategies, better guidance, early counselling, and enrolment in clinical trials. However, its application in clinical practice needs good collaboration between psychiatrists and neurologists. We aimed to review the literature for studies highlighting the need for such collaboration.MethodWe performed a scoping literature review on early diagnosis of FTD, including suggested new biomarkers and psychometric studies supporting the diagnosis.ResultThe search identified a recent publication on proposed research criteria for prodromal bvFTD. These criteria were developed and validated by the ALLFTD Consortium. For the early detection of FTD, the investigators stressed the need to refine the definitions of neuropsychiatric disorders in neurodegenerative diseases differentiating them from primary psychiatric disorders, to conduct psychometric assessment to detect executive dysfunctions in patients presented with psychiatric disorders, lowering the threshold of suspicion, applying some tests for social cognition, and to use plasma and CSF biomarkers to support the diagnosis. It was considered important to use culturally adapted psychometric batteries for assessment of executive function and social cognition.ConclusionCollaboration between neurologists and psychiatrists will be needed to translate research criteria into clinical practice for the early diagnosis of patients with FTD. The current search for feasible biomarkers to improve the diagnostic utility is important and should be encouraged among psychiatrists as well as neurologists.
Multi‐omic profiling of isogenic ApoE3/3 and ApoE4/4 iPSC‐derived astrocytes uncovers altered lipid metabolism and mitochondrial function of ApoE4 astrocytes
Authors: Koppes Sascha , Feringa Femke M , Robert Aiko , Kruijff Iris Daphne , Olivier‐Jimenez Damien , Erlebach Lena , Thompson Leslie M. , Kronenberg‐Versteeg Deborah , Ori Alessandro , Mohammed Yassene , Giera Martin , van der Kant Rik 
Published: December 2023

AbstractBackgroundAs the main genetic risk factor for AD, glial ApoE4 has been implicated in a number of early disease relevant processes, such as lipid dyshomeostasis, mitochondrial dysfunction and altered immune function. This ApoE4 glial phenotype is not yet well characterized and this hampers the rationale design of ApoE4‐targeting interventions.MethodWe characterize the phenotypes of ApoE3/3 and ApoE4/4 iPSC‐derived astrocytes by multi‐omic profiling. In addition, we use lipidomic and metabolic profiling of interventions in ApoE4 astrocytes to define compounds that normalize lipid counts and metabolic function.ResultIn the ApoE4 astrocytes we observe strong accumulation of cholesterol esters (storage product of cholesterol) and triglycerides (storage products of fatty acids), in comparison to the ApoE3 astrocytes. Interestingly, our proteomic and transcriptomic profiling of these cells reveal an increase in cholesterol synthesis, despite the already high levels of cholesterol esters in the cell. Moreover, our proteomic and transcriptomic results display an increase in mitochondrial pathways, such as beta‐oxidation, TCA cycle and oxidative phosphorylation and a decrease in glycolysis. Not only mitochondrial function is altered but also mitochondrial organization, as we see an upregulation of the most relevant proteins for mitochondrial fusion, MFN1, MFN2 and OPA1. Our lipidomic and metabolic profiling of ApoE4 astrocytes after treatment with a number of different interventions reveals new insights into these altered lipid metabolic pathways.ConclusionOur multi‐omic profiling of iPSC‐derived ApoE3/3 and ApoE4/4 astrocytes uncovers that ApoE4 astrocytes have altered lipid metabolism, mitochondrial function and mitochondrial organization. Treatment with interventions reveals new insights into these altered pathways.