bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline characteristics in Japan‐multimodal intervention trial for prevention of dementia (J‐MINT) Tamba study
Authors: Ono Rei , Kowa Hisatomo , Oki Yutaro , Osaki Tohmi , Murata Shunsuke , Kumagai Ryoko , Uchida Kazuaki , Yasuda Hisafumi , Kido Yoshiaki 
Published: December 2021

AbstractBackgroundTo prevent Alzheimer’s disease, a multimodal intervention has been tried in world wide. J‐MINT is a trial in Japan and is studied in three different areas. J‐MINT Tamba, one of substudies of J‐MINT, has begun in September, 2020 in a Japanese rural area (UMIN000041938). The aim of this study is to report the characteristics of participants at the baseline, especially focusing on APOE subtypes and their cognitive functions.MethodThis study was cross‐sectional design. The inclusion criteria in this study were as follows; 1) Tamba citizen aged 65‐85 at the time of enrollment, 2) 24 or higher in the Mini‐Mental State Examination, and 3) having at least 1 of the following vascular risks (Treating hypertension or having systolic BP >=140 mm Hg or diastolic BP >= 85 mm Hg and treating diabetes or HbA1c >=6.0%). Cognitive functions were evaluated by following tests; the Trail Making Test (TMT) part A and part B, forward digit span, backward digit span, the Digit Symbol Substitution Test (DSST), the logical memory test from WMS‐R (immediate and delayed recall), and the Free and Cued Selective Reminding Test (FCSRT). The APOE epsilon 4 carrier or noncarrier were identified by serum blood test. Additionally, life‐related factors and number of drug use and type were assessed by self‐reported questionnaire. We performed statistical analyses using multiple regression, with each cognitive function as the dependent variables, the APOE epsilon 4 carrier and the other factors (and interaction) as the independent variable, and age and sex as confounding variables.ResultTotal 203 elderly were registered (mean age: 73.9 ± 4.8 years, females: 71.4%). The number of participants of APOE epsilon 4 carrier were 18.6% and that of participants with polypharmacy were 35.8%. Although the cognitive functions were not related with the APOE epsilon 4 carrier, TMT part A and DSST were observed the interaction between the APOE epsilon 4 carrier and polypharmacy (coefficient: 16.2, p values < 0.01; ‐10.1, 0.03).ConclusionCoexistence of APOE epsilon 4 and polypharmacy showed lower cognitive functions in spite of the community‐dwelling elderly with normal cognition. These elderlies might develop cognitive decline in early phase.
Task‐free functional networks related to emotion processing in frontotemporal lobar degeneration
Authors: Canu Elisa , Calderaro Davide , Castelnovo Veronica , Leocadi Michela , Basaia Silvia , Filippi Massimo , Agosta Federica 
Published: December 2021

AbstractBackgroundNonverbal communication is a crucial aspect of interpersonal relationships, and defective emotion recognition can lead to altered social interactions. The aim of our study was to investigate the relationship between emotion processing and resting‐state functional connectivity (RS‐FC) in frontotemporal lobar degeneration (FTLD).Method80 FTLD patients and 65 age‐matched healthy controls underwent brain 3.0 Tesla MRI [3DT1‐weighted and RS‐functional MRI (RS‐fMRI)] and neuropsychological assessment, including the Comprehensive Affect Testing System (CATS). FLAME models in FSL were performed between each emotion construct and RS‐FC changes within crucial networks.ResultFTLD patients performed worse than controls in all CATS‐subtests. In controls, a high performance at the emotion naming and emotion matching constructs was related with increased RS‐FC within the cerebellar network, and a high performance at the emotion discrimination construct was related with increased RS‐FC of the right occipital face area (OFA) within the visuo‐associative network. In FTLD patients, high performances at the emotion naming construct were related with increased RS‐FC of the bilateral OFA within the visuo‐associative network and the bilateral frontal pole within the default‐mode‐network, whereas high performances at the emotion matching construct were related with increased RS‐FC of the left OFA within the visuo‐associative network. Finally, in FTLD patients, high performances at each emotional construct were related with decreased RS‐FC within the basal ganglia network.ConclusionIn healthy controls and FTLD patients, the RS‐FC within crucial networks is related to different constructs of emotion processing. In FTLD, the RS‐FC associated with emotional performances involved a large number of brain regions, likely due to brain functional specificity loss and compensatory attempts. These findings offer potential markers for detecting functional vulnerability linked to social interactions.
Disclosures. Supported by the Italian Ministry of Health (GR‐2013‐02357415); European Research Council (StG‐2016_714388_NeuroTRACK).
Investigating the impact of scatter correction on Centiloid
Authors: Li Shenpeng , O'Keefe Graeme , Gillman Ashley , Burnham Samantha C , Masters Colin L , Williams Robert , Rowe Christopher C , Fripp Jurgen , Bourgeat Pierrick , Villemagne Victor L , Dore Vincent 
Published: December 2021

AbstractBackgroundCentiloid (CL) is a semiquantitative measure of amyloid‐β burden based on the ratio between neo‐cortical target region and the whole cerebellum. Photon scatter is one of the major sources of noise in PET data. Scatter correction methods are very different across PET cameras. In this study, we investigate how scatter correction affects the CL for inter/intra‐cameras by comparing PET images with/without scatter correction.Method203 subjects (Siemens mCT Biography (N=109), Philips Gemini TF 64 (N=94)) from the AIBL study were scanned with 18F‐NAV6240. All PET images were reconstructed off‐line with scatter correction enabled and then disabled. All images were processed by CapAIBL to generate CL values. The ΔCL, which was calculated as the difference between the scatter corrected CL and non‐scatter corrected CL, was investigated to quantify the impact of scatter correction. For the intra‐camera comparison, all subjects were categorised in three groups based on the head tilt along anteroposterior axis compared to the MNI‐152 template. For inter‐camera comparison, the head tilt angle was included as covariate into an ANOVA. Hierarchical linear regressions that included head tilt and camera models were used as covariates to investigate their effect on CL.ResultFigure 1 shows that scatter correction has a larger impact on the cerebellum cortex than in neocortex. Figure 2 shows that scatter correction depends on the head position, and it has more impact on subjects with higher CL for both cameras. Figure 3 presents that scatter corrections from two different cameras have different impact on CL values. Both head tilt and camera model had an impact on the scatter correction with (F=19.5, p=1.67e‐5) and (F=109.4, p=1.1e‐20), respectively. The b coefficients were 0.38CL/degree for head tilt and 8.2CL for the camera model, where more scatter is corrected on the Siemens CT than on the Philips Gemini TF.ConclusionOur results show that difference in scatter correction from different cameras have a significant impact on CL, it is yet to be known whether it is caused by hardware difference or software difference. Additional investigations using test‐retest data is needed to further characterize the real impact of scatter correction on Centiloid.
Developing a blood‐derived gene expression biomarker specific for Alzheimer’s disease
Authors: Korukonda Anuradha , Dutkowski Janusz , Ronen Roy , Sachdev Pallavi 
Published: December 2021

AbstractBackgroundEarly detection, monitoring, and treatment of Alzheimer’s disease (AD) will require measurement of easily accessible and reliable fluid biomarkers. We compared brain and blood gene and pathway expression analyses to identify core features for discriminating AD from controls. The brain gene expression profile was generated using a dataset (GSE33000) from post‐mortem dorsolateral prefrontal cortex isolated from 624 AD patients and genotype‐matched control samples, while blood gene expression profiles were generated using GSE63060 (n=329) and GSE63061 (n=388) datasets derived from peripheral blood samples of two case‐controlled studies of the AddNeuroMed consortium.MethodThe gene expression datasets were retrieved from the Gene Expression Omnibus (GEO). Limma linear models were used to compute moderated T‐statistics and identify differentially expressed genes (DEGs) in the AD condition. Gene Set Enrichment Analysis (GSEA, applying the Piano R package to moderated T‐statistics from DEG analysis) was employed to identify significantly differentially regulated REACTOME and KEGG pathways. Comparison of the brain and blood‐derived analyses provided a common set of pathways modulated in AD patients.ResultDEG analysis revealed 680, 116, and 21 upregulated genes and 136, 160, and 45 downregulated genes in GSE33000 (Brain), GSE63060, and GSE63061 (Blood) datasets, respectively (FDR < 0.05; upregulated: FC > 1.15, downregulated: FC < 0.8). Differential pathway expression analysis using GSEA (FDR < 0.05) yielded 218, 196, and 202 REACTOME and 151, 69, and 125 KEGG pathways in GSE33000, GSE63060, and GSE63061 datasets, respectively.Notably, 21/115 and 56/103 up‐ and downregulated REACTOME pathways respectively, in the brain‐derived dataset were shared with the blood‐derived dataset (FDR < 0.05). Strikingly, 52.4% and 23.8% of the upregulated pathways were dominated by immune system and hemostasis, respectively. Meanwhile, 42.9% and 10.7% of the downregulated pathways included cell cycle and signal transduction pathways, respectively.ConclusionSystematic analysis of genes and pathways differentially expressed in AD samples across brain and blood identified common signatures reproducible across studies and showed potential for distinguishing between AD and control patients. Our results suggest the potential of employing a blood‐based gene expression panel for early diagnosis and disease monitoring of AD.
Multicenter reproducibility of quantitative susceptibility mapping of the entorhinal cortex and hippocampal subfields at 7T MRI
Authors: Adeyemi Oluwatobi F , Mougin Olivier , Bowtell Richard , Penny Gowland , Hosseini Akram A. 
Published: December 2021

AbstractBackgroundT2*‐weighted MRI images can be processed to produce quantitative susceptibility maps (QSM). These reflect iron and myelin concentrations, which are disturbed in neurodegenerative cascade and Amyloidb/tau pathological states. Changes in susceptibility have been measured in various regions of the brain in association with ADRD disease severity [Kim, et al.NeuroImage: Clinical. 2017], particularly in the hippocampus, amygdala, precuneus and thalamus, but no study has focused on subfields of the hippocampus in ADRD. As part of the UK7T Network’s “Travelling Heads” study [Clarke, et al. NeuroImage 2020], our aim here was to assess the inter‐subject and inter‐site reproducibility of QSM mapping at 7T in the entorhinal cortex, hippocampal subfields, and dentate gyrus preparing for future multi‐site clinical studies of Alzheimer’s disease and Related Dementias (ADRD).MethodTen healthy volunteers (3 female, 7 males; age 32.0±5.9 years) were scanned using harmonized single‐echo T2*‐weighted gradient echo, T1‐weighted and T2‐weighted sequences, as described in [Clarke, et al. NeuroImage 2020]. Participants were scanned five times at their “home” site on one of the following 7T MRI scanners: 1xPhilips, 2xSiemens Magnetom, 2xSiemens Terra scanners.ASHS [Yushkevich, et al. Human Brain Mapping. 2015] was used to segment the hippocampus from the combination of the high resolution T1 and T2 weighted data and a detailed atlas. The volume of each subfield was obtained from the segmentation using FSL (in CA2 and CA3 sub‐volumes were too small for these regions to be included in the susceptibility analysis.).QSM maps of the whole brain were produced using Multi‐Scale Dipole inversion (MSDI) [Acosta‐Cabronero, et al. NeuroImage. 2018] and the average and standard deviation of the susceptibility in each sub‐field in each scan was extracted.ResultThe median intraclass correlation coefficient (ICC) value for the susceptibility for each subfield was found to be 0.84, 0.48, 0.71, 0.83 and 0.78 for entorhinal cortex (ERC), subiculum (SUB), CA1, dentate gyrus (DG) and Tail, respectively.ConclusionSusceptibility can be measured with good reproducibility for the hippocampal subfields and entorhinal cortex in healthy subjects and this protocol can now be translated to clinical studies of ADRD.
A 13‐year longitudinal study of the impact of air pollution on cognition
Authors: Wu Jing , Grande Giulia , Stafoggia Massimo , Ljungman Petter , Laukka Erika J , Bellander Tom , Rizzuto Debora 
Published: December 2021

AbstractBackgroundAccumulation of evidence has raised concern regarding the harmful effect of air pollution on cognitive function, but results are inconclusive. We aimed to investigate whether long‐term exposure to air pollutants may have an adverse effect on cognitive function in older adults residing in an urban area.MethodData for this study were obtained from the Swedish National Study on Aging and Care in Kungsholmen. Cognitive impairment, no dementia (CIND) was assessed by a comprehensive neuropsychological battery. We assessed long‐term residential concentrations of particulate matters (PM2.5 and PM10) and nitrogen oxides (NOx) with land use regression. Long‐term air pollution was included as a time‐varying variable. Hazard ratio (HR) and 95% confidence interval (CI) were estimated with Cox proportional hazards. Departures from linearity were presented by fitting models with cubic splines with 3 knots at fixed percentiles (10th, 50th, 90th) of its distribution. We further explored the effect of long‐term air pollution exposure on the progression of CIND cases assessed at baseline to dementia incidence, using Cox hazard models.ResultAmong 2499 participants, 351 individuals developed CIND during the follow‐up. A 1‐μg/m3 increment in PM2.5 exposure was associated with a 63% increased risk of CIND incidence (HR=1.63, 95%CI: 1.44‐1.86). Weaker associations were found for PM10 (HR=1.06, 95%CI: 1.01‐1.11) and NOx (HR=1.01, 95%CI: 1.00‐1.02). Among those CIND cases at baseline (N=607), 118 participants developed dementia during follow‐ups. We observed an increased hazard of dementia for a 1‐μg/m3 increment in PM2.5 exposure in individuals with prevalent CIND at baseline, although non‐statistically significant (HR=1.24, 95%CI: 0.88‐1.74).ConclusionWe found suggestive evidence of an association between ambient air pollutants and incidence of CIND and its progression to dementia in older adults. Further research should focus more on the underlying mechanisms.
Self, insula and dementia with Lewy bodies
Authors: Tisserand Alice , Philippi Nathalie , Botzung Anne , Blanc Frédéric 
Published: December 2021

AbstractBackgroundThe objective is to review in the literature evidence of the relationship between the Self, the insular cortex, and Dementia with Lewy bodies (DLB). The notion of “Self” encompasses a subjective part that integrates the most internal bodily phenomena of self‐awareness, and an objective part that sustains autobiographical memory and its most specific details. Modifications of the Self, such as anosognosia and personal identity, or autobiographical memory deterioration, are frequently reported by relatives and noticed by clinicians, jointly with insular atrophy, which occurs early in the course of the disease.MethodWe performed research on PubMed and Google Scholar, using MeSH subheadings and keywords, limited to papers in English; 226 publications contributed to the review. The terms “Lewy bodies”, “Insula”, “Self” and different aspects related to the self, such as “subjective sense of self”, “self‐concept” and “autobiographical memory” were used to denote the themes of interest.ResultThe evidence suggest that insula is a multiconnected brain region involved in processing varied aspects of the self. On the one hand, insula’s posterior part integrates primary interoceptive representations through sensorimotor processes, and on the other hand insula’s anterior part sustains and integrates viscerosensory responses, socio‐emotional processing and cognitive functions, allowing the emergence of self‐awareness. In addition, changes in personal tastes resulting from insular atrophy have been highlighted in DLB. However, there is, to date, little work exploring the different components of the self (i.e. subjective sense of self; self‐concept; autobiographical memory) in DLB.ConclusionBased on our literature review, it seems that no experimental work have ever been performed on the Self in DLB. Numerous aspects related to the Self, from the most primitive to more elaborated ones are worthy of being studied in this affection, whose anatomic peculiarity sets in early insular damage. We intend to investigate these questionings in DLB, compared to Alzheimer disease – which is characterized by an early deterioration of episodic autobiographical memory – and healthy elderly population, by combining behavioral measures and multimodal neuroimaging, with a particular interest for the insular cortex.
Late‐life depression, allostatic load, and risk of dementia: The AGES‐Reykjavik study
Authors: Twait Emma L , Basten Maartje , Gerritsen Lotte , Gudnason Vilmundur , Launer Lenore J , Geerlings Mirjam I 
Published: December 2021

AbstractBackgroundThe biological underpinnings of the relationship between depression and dementia are currently not completely understood. Previous research has highlighted the role of vascular, metabolic, inflammatory, and stress markers in the role of both depression and dementia. Allostatic load has been an all‐encompassing term to describe these biological factors when investigating subgroups in individuals based on health characteristics. The current study aimed to elucidate if depression subtypes exist based on modifiable allostatic load factors using latent class analysis (LCA), and whether these subtypes have differing risk on incident all‐cause dementia, Alzheimer’s disease (AD), and non‐AD diagnosis using Cox regression analyses.MethodThe study included 5343 individuals without dementia at baseline from the AGES‐Reykjavik Study. Vascular factors (systolic blood pressure and pulse pressure), cholesterol (high‐density lipoprotein and low‐density lipoprotein), metabolic factors (abdominal circumference, fasting glucose, and triglycerides), inflammation (c‐reactive protein), and stress factors (salivary morning and evening cortisol) were used to indicate allostatic load. Both allostatic load indicators and depressive symptoms (Geriatric Depression Scale‐15) were assessed at baseline. Incident dementia was assessed after 12‐years follow‐up. Allostatic load indicators as well as each item on the GDS‐15 were used in the LCA.ResultLCA revealed that allostatic load factors, more than the depression questionnaire, grouped the individuals in this cohort. We identified six classes, named based on their most identifying characteristics: ‘Average’ (34% prevalence), ‘Cardiovascular + metabolic risk’ (27% prevalence), ‘Slim’ (16% prevalence), ‘Depressed’ (10% prevalence), ‘Hypertension’ (10% prevalence), and ‘Diabetic’ (4% prevalence). Cox regression analyses found an increased risk for incident all‐cause dementia in the ‘Slim’, ‘Depressed’, and ‘Diabetic’ groups. The ‘Slim’ group had a specific risk for AD, and the ‘Depressed’ group for non‐AD dementias.ConclusionThe findings suggest subgroups exist in older individuals based on allostatic load factors, with differing risk for incident dementia. This highlights the importance of early interventions in diabetes and depression and in monitoring for dementia symptoms.
Resting‐state alpha electroencephalographic rhythms are differently related to gender in cognitively unimpaired seniors and in patients with amnestic mild cognitive impairment due to Alzheimer’s disease
Authors: Lorenzo Ivan , Babiloni Claudio , Noce Giuseppe , Ferri Raffaele , Lizio Roberta , Lopez Susanna , Tucci Federico , Soricelli Andrea , Nobili Flavio Mariano , Arnaldi Dario , Famà Francesco , Giubilei Franco , Marizzoni Moira , Güntekin Bahar , Yener Gorsev , Stocchi Fabrizio , Frisoni Giovanni , Del Percio Claudio 
Published: December 2021

AbstractBackgroundHere we tested the hypothesis that gender may diversely affect resting state eyes‐closed electroencephalographic (rsEEG) alpha (8‐12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer’s disease and mild cognitive impairment (ADMCI).MethodClinical and rsEEG datasets in 69 ADMCI and 57 Nold individuals ‐ matched as demography, education, and gender ‐ were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. Each group was stratified into two subgroups based on gender (i.e., female and male).ResultAs compared to the Nold female subgroup, the male one showed greater reductions in the rsEEG alpha rhythms topographically widespread. In relation to the ADMCI female subgroup, the male one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions. Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions as revealed by neuroimaging, and clinical and neuropsychological scores.ConclusionThe present results suggest that gender may represent a deranging factor for dominant rsEEG alpha rhythms topographically widespread in Nold seniors and topographically posterior in ADMCI patients.