bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSF immune activation in Alzheimer’s disease driven by tau‐ and not amyloid pathology
Authors: Nordengen Kaja , Kirsebom Bjørn‐Eivind , Richter Grit , Pålhaugen Lene , Selnes Per , Gisladottir Berglind , Waterloo Knut , Rongve Arvid , Aarsland Dag , Fladby Tormod 
Published: December 2022

AbstractBackgroundGenetic studies suggest involvement of the immune system in Alzheimer’s disease (AD) development, and neuroinflammation has been suggested as a key driver of AD. We here employ cerebrospinal fluid (CSF) markers to study whether immune‐ and glial activation are primary features of early amyloid plaque deposition, or follow significant tau pathology as the disease progresses.MethodWe included n=267 non‐demented cases with repeated CSF samples (1‐6 years). The presence of amyloid pathology (A), tau‐tangle pathology (T) and neurodegeneration (N) using Aß42/40 ratio, p‐tau181 and total‐tau were determined at baseline and follow‐ups. We then selected participants (n=226) that remained stable A‐/T‐/N‐ (n=134), A+/T‐/N‐ (n=33) and A+/T+/N+ (n=34) over time and cases that progressed from A‐/T‐/N‐ to A+/T‐/N‐ (n=14) and A+/T‐/N‐ to A+/T or N+ (n=11). Other A/T/N categories (e.g. A‐/T or N+) were excluded. Mixed Linear Models (MLMs) were used to measure longitudinal changes in CSF sTREM2, YKL‐40, clusterin, fractalkine, MCP‐1, IFN‐γ, IL‐6, IL‐18 and IL‐10 between groups with stable A‐/T‐/N‐ group as the reference. All models included age, sex and number of APOEε4 alleles as covariates.ResultCompared to stable A‐/T‐/N‐, cases progressing from A‐/T‐/N‐ to A+/T‐/N‐ had lower sTREM2 levels (p=.022) over time, and both fractalkine (p=.053), IFN‐γ (p=.055) and clusterin levels (p=.068) showed trend levels towards lower levels. In stable A+/T‐/N‐ cases, YKL‐40 (p=.007) and fractalkine (p=.043) were lower than stable A‐/T‐/N‐ over time. A+/T+/N+ cases had markedly higher sTREM2, fractalkine and clusterin levels (all p<.001) that remained high over time. In this group the YKL‐40 levels were also higher at baseline (p<.001) and increased slightly over time (p=.032). There were no between‐group differences at neither baseline or over time in the CSF levels of MCP‐1, IL‐6, IL‐18 and IL‐10.ConclusionAmyloid pathology alone was not associated with increased immune and glial activation in our cohort, and several of the CSF immune markers were lower in both those progressing to A+/T‐/N‐ and the stable A+/T‐/N‐. An increase in activation markers was only shown in cases with tau‐pathology at baseline, or in cases that developed tau pathology during the follow‐up period, suggesting immune activation in response to tau pathology.
Changing views of old age and dementia for children in elementary schools in The Netherlands
Authors: Bormans Kasper , Zwakhalen Sandra ,   The department of Health Services Research is part of the Care and Public Health Research Institute (CAPHRI) of the Faculty of Health, Medicine and Life Sciences
Published: December 2022

AbstractBackgroundChildren have negative stereotypes about aging and dementia from a very young age. These mental images are harmful to their own well‐being in later life and toxic to their approaching behavior of elderly people. There is an urgent need for positive interventions that give children a more constructive image of old age and dementia.MethodWe organized an innovative 14‐week educational trajectory about positive aging for two school classes of Dutch pupils of 10 years old. The young participants (n = 40) received communicational training to interact in a meaningful way with grandparents and unfamiliar people with dementia. Before and after the intervention, the children made four drawings of elderly people (unfamiliar, healthy & happy, unhealthy & unhappy, grandparent). The evolution of the drawings will be analyzed with an emphasis on the appearance, the location, the activity and the social network of the elderly.Result
[Data will be collected in March – June 2022] We predict that the positive interventions will be visible in the evolution of the children’s drawings. We hypothesize the post‐test drawings to depict more social interactions between generations and showing a wider range of activities that differ from unhealthy and sedentary lifestyles.ConclusionThe negative perceptions about old age and dementia arise at a young age and are detrimental later in life. Positive interventions are able to alter these internalized representations by changing the perspective on old age and dementia in children.
Digitally enabled Cognitive Assessments in the Identification and Intervention for Dementia in Elderly Africans (IDEA) Study
Authors: Urasa Sarah , Boshe Judith , Paddick Stella‐Maria , Mushi Declare 
Published: December 2022

AbstractBackgroundThe Alzheimer’s Disease International (ADI) reports that the Sub‐Saharan African population age 65+ will double in less than 25 years. That compares to high income countries whose doubling of this same age group took between 45‐115 years. ADI estimates 7.2% dementia prevalence rate in those 60+ years old. Incidence rates have been estimated to be lower, 4.1/1000 person years for those ages 60‐64, which is lower than that of high income countries, but these data come from only 5 studies involving 6 cohorts; total n=9,494). The paucity of AD related research in Sub‐Saharian Africa is alarming given the aging demographics and requires an immediate and rapid response to drastically increase research efforts. The Tanzanian community‐based Identification and Intervention for Dementia in Elderly Africans (IDEA) Study is testing whether digitally enabled cognitive assessment methods will provide a framework from which to accelerate expanded AD related research in Sub‐Saharan African countries.MethodsThe IDEA study was initiatied in 2014. It has been longitudinally assessing participants (n=437), age 65 years and older through biennial examinations that includes dementia related risk factors including Sociodemographics, cognitive tests, medical history, blood pressure, and grip strength. To this protocol, and in collaboration with the Davos Alzheimer’s Collaborative Global Cohort Development program, will be added the collection of longitudinal AD‐related digital phenotypes through the use of a tablet in the clinic and through smartphone applications that can be self‐administered on a more frequent basis from the person’s place of residence.ResultsWe will present demographic and clinical characterization of the cohort to date. We will further discuss both the challenges and the opportunities provided through the added digital phenotyping protocol. We will also examine how being part of the DAC international network of research will help accelerate expansion of research not just within Tanzania, but potentially to other Sub‐Saharan countries.ConclusionsDigital assessments offer a feasible and cost effective method for expanding dementia research in lower income regions who are facing near term realities of an aging population, but are still lagging in research that can inform healthcare preparedness.
Association of plasma inflammatory and metabolic biomarkers with plasma ADRD biomarkers in community‐dwelling older adults
Authors: Parker Daniel C , Kraus William E. , Huffman Kim M. , Morey Miriam C. , Hall Katherine S. , Cohen Harvey Jay 
Published: December 2022

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) are associated with changes in inflammatory and metabolic biomarkers. Here, we evaluated associations among inflammatory and metabolic biomarkers previously‐associated with age related‐morbidity and plasma p‐Tau181, Aβ‐42/Aβ‐40 ratio, neurofilament light (NfL), and glial fibrillary acid protein (GFAP) in community‐dwelling older adults.MethodWe evaluated cross‐sectional associations of a panel of inflammatory and metabolic biomarkers with plasma ADRD biomarkers – quantified using the Quanterix SIMOA platform – in a subset of older adults from the Duke Performance Across the Lifespan (PALS) study (N=317; Age=75±8.6; MoCA=25±3.4). Inflammatory and metabolic biomarkers included TNF‐α, TNFR‐I, TNFR‐II, d‐dimer, IL‐6, VCAM‐1, G‐CSF, RANTES, MMP3, paraoxonase activity, adiponectin, uric acid, 11 free amino acids, and 45 acylcarnitines. We applied principal components analysis (PCA) separately to the inflammatory biomarkers, amino acids, and acylcarnitines. We used multivariate multiple regression to associate biomarker PCs with ADRD biomarkers, adjusting for age and sex.ResultBiomarkers were not normally‐distributed and were log‐transformed prior to PCA. We identified 3 inflammatory principal components (PCs), 5 acylcarnitine PCs, and 2 amino acid PCs. Of these, two inflammatory PCs, one acylcarnitine PC, and one amino acid PC were associated with plasma ADRD biomarkers (all Wilk’s Λ p<0.01). On univariate analyses, one inflammatory PC loading positively on G‐CSF and RANTES associated with lesser concentrations of p‐Tau181, NfL, and GFAP (all p<0.05). An amino acid biomarker PC loading positively on hydrophobic amino acids associated with lesser concentrations of NfL and GFAP (all p<0.001). An inflammatory PC loading positively on TNF‐α, TNFR‐I, TNFR‐II and IL‐6, and d‐dimer associated with greater concentrations of p‐Tau181 and NfL (all p<0.01). An acylcarnitine PC loading positively on short‐chain acylcarnitines was associated with greater concentrations of NfL (p<0.001). None of the biomarker PCs significantly associated with the Aβ‐42/Aβ‐40 ratio.ConclusionIn community‐dwelling older adults, biomarker PCs loading on G‐CSF, RANTES, and hydrophobic amino acids were associated with lesser concentrations of some plasma ADRD biomarkers, while an inflammatory PC loading on TNF‐α, TNFR‐I, TNFR‐II, and VCAM‐1 was associated with greater concentrations. Our findings provide insight into the association of inflammatory and metabolic biomarkers with plasma biomarkers of ADRD pathology.
The effects of 12‐week mobile phone based cognitive intervention on brain function in patients with mild cognitive impairment
Authors: Kim Bori. R. , Jeong Jee Hyang , Kim Geon Ha 
Published: December 2022

AbstractBackgroundCognitive intervention (CI) has been known to improve cognition and to delay cognitive decline in patients with mild cognitive impairment (MCI). The purpose of this study was whether our newly developed, mobile‐phone based CI with a chat bot for 12 weeks changed brain function and cognitive performance in patients with MCI.MethodsA single‐blind randomized controlled trial was conducted in 60 older adults with patients with amnestic MCI. Participants were randomized into the two groups: the mobile phone based CI with chat bot (CI) (n=30) group and waitlist control group without CI (Control) (n=30) groups. A total of 13 mobile‐phone based CI programs were developed targeting for attention, memory, visuospatial, calculation, language and frontal executive functions. The CI comprised 60‐min‐session per day for 12 weeks. The primary outcome was the changes in brain function measured by resting state electroencephalogram (EEG), which was measured in eyes open and eyes closed conditions for 3 minutes each, with a 19‐channel wireless EEG device. The secondary outcome was the changes of cognitive function measured using the Cambridge Neuropsychological Test Automated Battery.ResultsThere were no baseline demographic and clinical differences between the CI and the control groups. EEG analysis after 12‐week showed increased beta wave on the frontal areas in the CI group, while decreased beta wave on the frontal areas in the control group. In addition, CI group also demonstrated improvement in attention domain compared to the control group.ConclusionConsidering that increased beta wave is associated with attention performance, our results suggest that the 12 week mobile‐phone based CI with chat bot could help improve brain function in patient with MCI.
The Relationship of Perceived Health Literacy and Vaccination Hesitancy in People with Dementia Associated Disorders
Authors: Kaczmarek Olivia , Baek Steven , Peraza‐Bonilla Sophia , Teng Ellie , Sethi Avtej , Bumstead Barbara , Zarif Myassar , Gudesblatt Mark 
Published: December 2022

AbstractBackgroundDementia associated disorders (DAD) refers to clinical conditions that are typically characterized by progressive cognitive impairment (CI) that interferes with an individual’s ability to function independently. In routine care CI in DAD may be poorly recognized and can vary considerably in degree and combination across multiple cognitive domains. Therefore, clinical judgement may be insufficient alone to identify CI across these varied types/degrees, and how CI may directly affect both patient quality of life and decision‐making. Patient reported outcomes (PRO) are used to survey patient perception of their disease across varied real world impact. The BRIEF Health Literacy (HL) survey (BHL), Electronic health literacy (eHealth Literacy Scale, EHL) and the psychological antecedents of vaccinations (Vaccine 5C, V5C), vaccine hesitancy, have not been explored across these areas in people with DAD (PwDAD).MethodRetrospective cross‐sectional analysis of PwDAD who completed the following PRO’s V5C, EHL, and BHL in routine care.Results146 PwDAD, average age of 72+/‐15 years. Linear regression statistics were used to analyze trends between individual V5C questions with the BHL and EHL. Significant correlations were found as follows (p<0.01): V5C‐2 (the need for vaccination)vs BHL (r = .2), V5C‐3 (everyday stress interfering with vaccination) vs BHL (r = .2), V5C‐4 (I personally weight risks/benefits of vaccination) vs BHL (r = .3), V5C‐2 vs EHL (r = .2), V5C‐3 vs EHL (r = .1), V5C‐4 vs EHL (r = .2).ConclusionLower perception health literacy ability (BHL) and lower ability to use electronic sources to gain information regarding their health literacy (EHL)in PwDAD impact decision and feelings regarding vaccination (i.e. the necessity of vaccination, stress as a barrier to vaccination, and risk‐benefit analysis respectively). Further investigation beyond perceptions to quantitative measures of CI across multiple cognitive domains (degrees/combinations) between the V5C, BHL, and EHL would prove useful in exploring these relationships and defining a path to enhance education to reduce vaccine hesitancy.
Relationships between metabolic activity in the brain and circulating metabolites vary by sex
Authors: Vu Michael M , Zammit Matthew D , Bansal Shivani , Gross Thomas J , Cheema Amrita K , Christian Bradley T , Mapstone Mark 
Published: December 2022

AbstractBackgroundGlucose hypometabolism in the brain measured by [F‐18] fluorodeoxyglucose (FDG) positron emission tomography has been observed in a number of neurological disorders. In both Down syndrome (DS) and non‐DS populations, it is associated with higher amyloid load and lower cognitive performance.MethodWe obtained plasma samples, FDG PET and [C‐11] Pittsburgh compound B (PiB) from a sample of 89 adults with DS (mean age [standard deviation] = 38.9[8.3] years). We measured levels of metabolites using targeted mass spectrometry. We calculated correlation constants between glucose uptake in discrete brain regions, global amyloid load, and plasma metabolite levels. We examined the effect of sex and age on these correlations.ResultWe found significant correlations between plasma metabolites, primarily lipids, and FDG PET signal in the brain with regional specificity. Additionally, metabolites which were positively associated with FDG PET signal in a specific brain region were negatively associated with amyloid load and vice versa. While FDG PET signal in each region were not significantly different between males and females, their correlation with metabolites did. When examining females only, we find primarily lipid correlates again. The lipid metabolites negatively associated with FDG PET signal were distinguished from those lipids positively correlated with FDG PET signal by lipid class and not fatty acid length. In males, a completely distinct set of associations between brain regions and metabolites were observed. The number of FDR significant correlations decrease dramatically, however the magnitudes of these correlation constants are higher than those observed in females and there is very little overlap between any of the brain regions correlated with each metabolite.ConclusionThe levels of brain amyloid and regional brain glucose metabolism in adults with DS are both reflected in the concentration of certain metabolites measured in blood plasma. Surprisingly, each brain region has its own orthogonal metabolic correlate. Moreover, these relationships are distinct in males and females. It will be important to explore the basis for these differences and determine if they are present in the general population. Future metabolic analysis of neurological diseases could also benefit from separate analysis in males and females so as not to obscure these differences.
Cohort Profile: The Community‐based Cohort of Functional Decline in Subjective Cognitive Complaint elderly study of the Geroscience Center for Brain Health and Metabolisms (GERO)
Authors: Slachevsky Andrea , Peters Anne , Zitko Pedro , Lillo Patricia , Thumala Daniela , Demanet Michele , Villagra Roque , Cerda Mauricio , Ibáñez Agustin , Gonzalez Christian 
Published: December 2022

AbstractBackgroundDementia worldwide is one of the most important causes of disability in the elderly and the most rapidly growing cause of death in the last 20 years in Chile. Cognitive complaint is considered a predictor for cognitive and functional decline (FD), incident mild cognitive impairment, and incident dementia. The GERO cohort aims to determine multidimensional risks factors associated with the prognosis of elderly with cognitive complaint on DF.MethodThe GERO cohort is a prospective cohort study of community‐dwelling elderly with cognitive complaint, without dementia, aged 70 or older living in 4 municipalities in Santiago, Chile. Participants were identified by a household census and information on demographics, biomedical, psychosocial, neuropsychological, neuropsychiatric, and motor function were collected by means of questionnaires and evaluations. Neuroimaging, blood, and stool samples were also obtained. FD was measured by the Pfeffer (score range 0‐33), Technology Activities of Daily Living Questionnaire (T‐ADLQ, score range 0‐100), and Everyday Cognition (ECOG, score range 0‐36) questionnaires.ResultA total of 17,759 households were successfully approached, identifying 2,533 eligible subjects, accepting to participate 299 (59 men; 240 women). The mean age was 76.8±5.1, 25% older than 79. The average years of schooling was 8.9± 4.8. None of participants showed underweight. The average score for the Mini‐mental State Exam (MMSE) was 27.1± 2.4, with 5.3% of the sample scoring less than 23. The mean values for Pfeffer, T‐ADLQ, and ECOG were 0.8±1.3, were 11.9± 10.3, and 0.4±0.4 respectively. In the multivariate analysis MMSE was inversely correlated with the ECOG score (regression coefficient: ‐0.03 [95%CI ‐0.07; ‐0.002]. Pfeffer also was associated, but its statistical significance was lost after the multivariate adjustment.ConclusionFew other studies addressed cognitive complaint and functionality in elderly recruited at home. Elderly in the GERO‐cohort with cognitive complaint, without dementia, show a good level of functioning at the first assessment. Cognitive function measured by the MMSE seems to be associated to a subtle decline in general functioning as everyday cognition. Future multidimensional and prospective analysis of this cohort could bring more information about this association.
Is rs242561 a regulator of tau expression in adult mice?
Authors: DAS Rueben G , Choi Eirene , Sgourdou Paraskevi , Bernard Tia , Dombroski Beth A. , Schellenberg Gerard D. 
Published: December 2022

AbstractBackground
Microtubule associated protein tau (MAPT) is a major risk gene for multiple neurodegenerative diseases including Progressive supranuclear palsy (PSP), Corticobasal degeneration (CBD) and Alzheimer’s disease (AD) where disease specific imbalance in 3R: 4R tau isoforms is noted. Since pathogenic mutations in the coding region of MAPT is minimal in these diseases, it is likely that the deviation from the normal equimolar concentration of 3R: 4R tau is due to altered regulation through its regulatory elements. One such potential regulator is suspected to be MAPT intronic SNP, rs242561. This SNP lies within NRF2‐bound anti‐oxidant response element and is actively transcribed in hippocampus but repressed in most non‐brain tissues. It is also a chromHMM enhancer in substantia nigra. However, expression studies on this SNP are discordant and inconclusive. In the present study we investigate whether rs242561 has any role in tau regulation in mice.MethodWe deleted 756 bp sequence encompassing the syntenic base of rs242561 in mouse by CRISPR‐Cas9 genome editing. Brain tissues from cortex, cerebellum and hippocampus were dissected from adult wild type, heterozygous and homozygogus mice with the deletion to study expression of tau.ResultWe observed reduced level of tau in cortical tissues of adult heterozygous and homozygous mice (heterozygote< homozygote) than the wild type but not in hippocampus and cortex.ConclusionOur preliminary study suggests rs242561 might have a role in regulating the expression of tau in adult mice cortex.
Vascular and Microstructural Markers of Cognitive Pathology
Authors: Coffin Claudia Ashlyn , Suerken Cynthia , Bateman James R. , Whitlow Christopher T. , Williams Benjamin J. , Espeland Mark A. , Sachs Bonnie C. , Cleveland Maryjo , Yang Mia , Rogers Samantha D. , Hayden Kathleen M. , Baker Laura D. , Williamson Jeff D. , Craft Suzanne , Hughes Tim M. , Lockhart Samuel N. 
Published: December 2022

AbstractBackgroundArterial stiffness may play a role in the development of dementia, presumably through its effects on white matter integrity and hyperintensities (WMH). However, relationships among arterial stiffness, white matter microstructure, and WMH volumes remain poorly understood. Arterial stiffness increases monotonically with age and its increase is accelerated by cardiometabolic disorders (e.g., hypertension , metabolic syndrome, diabetes). Further exploration of these relationships is key to the development of targeted therapies, early management, and detection.MethodArterial stiffness was measured using carotid‐femoral pulse wave velocity (cfPWV) in ADRC participants with baseline systolic blood pressure (SBP) measurements, detailed cognitive testing, cognitive adjudication, and brain MRI. We examined associations of cfPWV and SBP with cognitive function (Montreal Cognitive Assessment [MoCA], Preclinical Alzheimer’s Cognitive Composite [PACC5], and domain measures of memory and executive function) and brain MRI measures of: macrostructure (volume of gray matter [GM] and WMH from T1‐weighted and FLAIR imaging), white matter microstructure (neurite orientation dispersion and density imaging [NODDI] free water [FW] and diffusion tensor imaging [DTI] fractional anisotropy [FA]), and cerebral blood flow (CBF) in white matter (WM) and GM. Age, race, gender, education, and APOE‐4 status were included as covariates and in interaction terms in linear regression analyses.ResultAmong 458 participants with a mean age 70±8 years and cognitive adjudication (44 dementia, 157 MCI, 257 normal cognition; Table 1), higher cfPWV was associated with worse cognitive performance (MoCA, PACC5), as was SBP (MoCA, PACC5, executive domain, language domain; Table 2). Higher cfPWV was associated with differences in WM microstructure (higher FW, lower FA) and higher WMH volume. While no overall associations between cfPWV and CBF were detected, cfPWV had stronger associations with FW, FA, and WMH in men. Higher SBP was associated with higher FW, higher WMH volume, and lower WM and GM CBF (Table 3). SBP had stronger associations with WMH in younger participants (<70y) and GM CBF in Black/AA participants and participants with impaired fasting glucose. No other interactions were detected.ConclusionsArterial stiffness is associated with microstructural and macrostructural differences and poorer global and executive cognitive function.