bluuebunny/crossref_metadata_2025_split huggingface dataset:
Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG) study and Tata Longitudinal Study on Aging (TLSA): Study protocols
Authors: Sundarakumar Jonas , Chauhan Ganesh , Rao Girish N , Sivakumar Palanimuthu T , Rao Naren P , Ravindranath Vijayalakshmi ,   SANSCOG and TLSA Investigators
Published: December 2020

AbstractBackgroundPopulation‐based, prospective, longitudinal, aging and cognition studies are an important approach to understand the pathophysiology of normal and pathological cognitive aging. However, till date there are no comprehensive cohort studies from the Indian population, examining clinical, cognitive phenotypes and associated genetic and neuroimaging correlates.MethodThe Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG) study and the Tata Longitudinal Study on Aging (TLSA) are envisioned as parallel and synchronized, prospective, community‐based cohort studies in India – rural and urban, respectively – with long term follow‐up over many years, for comprehensive evaluation of risk and protective factors associated with cognitive changes due to normal ageing, dementia and other related disorders (n=10,000 for SANSCOG and n=1,000 for TLSA). Both the study cohorts comprise of cognitively healthy individuals aged ≥ 45 years. However, they have distinct population characteristics. Participants in the SANSCOG study are recruited from the villages of Srinivaspur Taluk in Kolar District in southern India, through an area sampling strategy, whereas, those in TLSA are recruited through convenience sampling, from urban Bangalore. Participants are evaluated with detailed clinical, neurocognitive, lifestyle, anthropometric, biochemical and genetic assessments in the baseline visit and during periodic follow‐up visits. End‐to‐end digitization has been done for all the assessments. GWAS, Whole Genome Sequencing & MRI (resting fMRI, structural MRI, DTI & MRS) is being done in a subset of the SANSCOG study cohort (n=1,000) and the entire TLSA cohort (n=1,000).ResultThese parallel cohort studies will generate a database comprising of genetic, biochemical, clinical, neuroimaging and neurocognitive data that can help in further exploration of the pathophysiology of normal and pathological cognitive aging using systems biology‐based approaches. Though these two cohorts are contrasting with respect to socio‐economic status, migration, literacy and lifestyle, the harmonization in the assessments across the two studies offers a unique opportunity to compare outcome measures across these two groups.ConclusionSANSCOG and TLSA studies are landmark cohort studies in India, which employ a combined multi‐level approach, spanning genotype to phenotype and will be able to provide reliable biomarkers to predict the risk factors for development of dementia in the Indian population.
Altered serum levels of proteins involved in beta‐amyloid clearance in the aftermath of the Kumamoto magnitude 7.3 earthquake
Authors: Uchida Kazuhiko , Sato Tadashi , Tanaka Motomi , Oniki Kentaro , Saruwatari Junji , Itai Yaeko , Takahashi Noriaki , Matsuda Hiroshi , Osame Mitsuhiro 
Published: December 2020

AbstractBackgroundOur previous studies revealed that apoA‐I, transthyretin, and complement component 3 (C3) in serum were associated with cognitive decline, and that atrophy of atrophy of the medial temporal structures was associated with decreased levels of apoA‐I1,2). Increased risk of dementia was observed in the aftermath of disaster like earthquake and tsunami. The 2016 Kumamoto Earthquake, which was featured twice strong earthquakes of seismic intensity 7 and aftershock activities in the long period, produced house damaging and persistent and strong stress in people. In present study, we analyzed the levels of the blood‐based biomarker and hippocampal atrophy in the aftermath of the earthquake.MethodWe obtained the data of serum biomarker levels and MRI imaging at every 6 month during the 3 years after the 2016 Kumamoto Earthquake and also those at 6 months before the earthquake. In total, 111 serum marker‐test results were obtained from 6 months before to 42 months after the earthquake. Atrophy of the medial temporal structures was measured by the semi‐quantified VSRAD score in about 1,000 subjects.ResultSerum transthyretin and C3 levels were decreased at 6 months after the earthquake, and continue lower levels until 12 months. We calculated values of composite makers of these 3 proteins and determined cut‐off level which discriminated MCI from non‐demented control. The positive rate using cut‐off value before the earthquake was increased to 44% at 6 months, and it reduced to 10% at 18 months after the earthquake. Significant reduction of the hippocampal volume in male at 24 and 36 months was observed, on the other hand, there is no significant change in hippocampal volume in female. Interstingly, seum ApoA‐I levels were decreased in male and increased in female after the earthquake, and significant relationship between apoA‐I levels and hippocampal volume.ConclusionBlood‐based biomarkers related to Aβ clearance might be useful to grasp cognitive decline prior to neuroimaging changes in progression of cognitive impairment. Resources: 1) Lui S, et al. Alzheimers Dement (Amst), published online Dec 18 (2018); 2) Uchida K, et al. Alzheimers Dement (Amst) 1:270‐280 (2015).
Association between visceral fat amount and brain cortical thinning in the community‐dwelling elderly population
Authors: Noh Young , Cho Jaelim , Seo Seongho , Kim Woo‐Ram , Park Kee Hyung , Kim Changsoo 
Published: December 2020

AbstractBackgroundDespite emerging evidence suggesting that visceral fat may play a major role in the neurotoxic effect of obesity, no study has investigated the association between visceral fat amount and cortical thickness in the elderly. We examined the association of abdominal fat amount with cortical thickness and subcortical structures in the elderly.MethodCommunity‐dwelling individuals (≥60 years of age) without known neurological diseases (n=316) were included. Areas of subcutaneous fat and visceral fat were estimated from computed tomography scan. Regional cortical thicknesses and subcortical volumes were obtained by analyzing brain 3T magnetic resonance imaging. A generalized additive model was built to explore non‐linearity between abdominal fat amount and cortical thickness. A generalized linear model was used to explore the brain imaging markers associated with an increase in abdominal fat amount (quintiles used for cortical thickness).ResultThere were inverted U‐shape relationships of visceral fat amount with global (p=0.02), frontal (p=0.02), temporal (p=0.02), and parietal thicknesses (p<0.001). The quintile 5 (the highest) group had significantly thinner cortices compared with the quintile 3 group in the global (β=‐0.04, p=0.004), parietal (β=‐0.04, p=0.01), temporal lobes (β=‐0.05, p=0.002), cingulate (β=‐0.06, p=0.01), and insula (β=‐0.06, p=0.02). The higher amount of visceral fat was significantly associated with the smaller volume of the pallium (β=‐0.66, p=0.01) and putamen (β=‐1.36, p=0.03). Most of the associations between subcutaneous fat amount and the brain imaging markers were not significant.ConclusionWe found an inverted U shaped relationship between visceral fat amount and cortical thickness in elderly individuals. Future studies are needed to elucidate causal relationships and explore other factors which may be confounders.
Stroke memory rehabilitation (SMaRT) programme for mild ischemic stroke: Preliminary findings
Authors: Ong Angeline , Wong Fennie , Ng Sheng Chun , Leong Man Qing , Chua Esther Vanessa , Kandiah Nagaendran 
Published: December 2020

AbstractBackgroundThere are 6000‐7000 stroke survivors yearly in Singapore with about 40% being at risk for post‐stroke cognitive impairment (PSCI). Stroke Memory Rehabilitation (SMaRT) programme was designed to reduce the incidence of PSCI, facilitate transition back to the community, improve the mood and quality of life of patients with mild ischemic strokes. We report the preliminary outcomes of the program.MethodParticipants who attended the programme from April 2018 to Dec 2019 were included in this study. Each patient attended 8 two‐hour sessions over 8 weeks, focusing on cognitive processes (episodic memory, executive function and visuospatial function); healthy lifestyle habits, relaxation techniques and goal setting. All patients were administered neuropsychological assessments and questionnaires pre‐programme, 8 weeks and 6 months post‐programme. Paired sample t‐tests were applied to evaluate the changes in scores over the four time points on each outcome measure, subject to Bonferroni correction for family‐wise errors.Result156 participants (mean age=63.53 years, SD=9.63; mean education=9.95 years SD=4.18, 65.4 % male). Significant improvements in all outcome measures were observed from pre‐programme to all other time points. Cognitive scores significantly improved from pre to post‐programme and pre to 6 months post‐programme on the Montreal Cognitive Assessment (24.52 to 25.36; p<.001 and 25.05 to 25.98; p<.001 respectively); Visual Cognitive Assessment Test (VCAT) Score (22.67 to 24.14; p<.001 and 22.63 to 24.92; p<.001). Scores for Trail Making Test‐A only significantly shortened from pre‐ to 6 months post‐programme (52.00 to 45.52; p<.001). Depression levels significantly reduced on the Geriatric Depression Scale (4.01 to 3.29; p=.001 and 3.46 to 2.33; p<.001). Activities of daily living measured on the NEADL significantly improved (52.24 to 55.15; p<.001 and 52.48 to 56.27; p<.001). Quality of life (DemQOL) also significantly improved (88.77 to 91.88; p=.006 and 91.83 to 95.52; p<.001).ConclusionPreliminary findings demonstrate encouraging improvement in global cognition, executive function, quality of life, depression and activities of daily living from pre‐programme to 8 weeks and 6 months post‐programme. A multi‐approach structured cognitive rehabilitation programme for stroke survivors may thus be useful in preventing post‐stroke dementia.
Greater than the sum: Federated analyses in Alzheimer’s disease using the Human Brain Project Medical Informatics Platform (MIP)
Authors: Sokolov Arseny A. , Phenix Thierry , Chaptinel Jérôme , Leroy Melanie , Kherif Ferath , Redolfi Alberto , Pasquier Florence , Démonet Jean‐François , Ryvlin Philippe 
Published: December 2020

AbstractBackgroundThe abundance of patient data collected during clinical routine is rarely harnessed towards progress in neuroscience. However, multimodal real‐life data may provide significant insights into pathophysiology, disease progression and prognosis, in particular in the field of Alzheimer’s disease. The aim of the Medical Informatics Platform (MIP) within the Human Brain Project is to create an intuitive interface that allows remote computational analyses of clinical data stored in the respective medical centers.MethodThe concept of federated analyses refers to the statistical processing of physically separate and non‐aggregated data sets in a single user interface. The MIP interface provides advanced statistical approaches, remote data access and local user regulations. Authorized MIP users are able to test their hypotheses using a flexible portfolio of data sets, modalities and data processing tools.ResultAt the present stage, three memory clinics have contributed to the MIP: the Leenaards Memory Centre at the University Hospital Lausanne, Switzerland; the University Hospital Lille Memory Centre, France; and the IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli di Brescia, Italy. The data sets contain demographic, neuropsychological and volumetric MRI data from 5154 individuals with subjective and mild cognitive impairment or dementia. The data include clinically probable Alzheimer's etiology according to CSF biomarkers. Proof‐of‐concept and validation analyses will be presented. Reference data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which can be downloaded by MIP users in accordance with ADNI rules, can be compared with the clinical data in the MIP.ConclusionFederated analyses such as afforded by the MIP within the Human Brain Project do not only allow novel scientific insights due to a substantial increase in sample size and cross‐validation, but also ensure a high level of data protection. The MIP has a considerable potential for discovery in clinical neuroscience.
Brain beta‐amyloid in twin pairs discordant for episodic memory performance
Authors: Lindgren Noora , Karjalainen Tomi , Ekblad Laura L. , Helin Semi , Karrasch Mira , Teuho Jarmo , Tuisku Jouni , Kaprio Jaakko , Rinne Juha O. , Vuoksimaa Eero 
Published: December 2020

AbstractBackgroundβ‐amyloid pathology (Aβ) and episodic memory (EM) impairment are biological and cognitive hallmarks of Alzheimer’s disease (AD). However, most studies on the Aβ–EM association have been conducted in unrelated individuals and cannot tell if this relationship is confounded by shared genetic and/or environmental effects. We investigated if cortical amyloid pathology‐EM relationship is evident within twin pairs: a design that controls for shared genetic (fully in monozygotic [MZ] and partly in dizygotic [DZ] pairs) and environmental effects.MethodWe studied 45 same‐sex (mean [SD] age = 72.9 [4.0] years; 18 women pairs) twin pairs. EM discordance was based on a mean of two verbal delayed free recall measures: Logical Memory and Word List Learning from CERAD‐NB. We also studied within‐pair differences in 3 continuous EM scores (verbal immediate free recall [VerIFR], verbal delayed free recall [VerDFR], and visual delayed free recall [VisDFR]) in relation to within‐pair differences in cortical amyloid pathology. Cortical amyloid pathology in AD signature regions was measured with carbon‐11‐labelled Pittsburgh compound B ([11C]PiB) and quantified as standardized uptake value ratio (SUVR) with cerebellar cortex as a reference region.ResultA total of 42 pairs were discordant for EM (23DZ/19MZ). Twins with poorer EM had higher cortical [11C]PiB SUVR compared to their co‐twins (1.44 vs 1.36), but this difference was not statistically significant (mean intra‐pair difference of 6% / 0.08 SUVR units [95%CI: ‐0.05; 0.20], P=0.23). Using continuous scores within all pairs, co‐twins with higher SUVR had poorer EM scores (Ps< 0.006): VerIFR (r= ‐0.42), VerDFR (r= ‐0.41) and VisDFR (r= ‐0.46). In DZs, within‐pair differences in EM scores were significantly related to within‐pair differences in SUVR with correlations ranging from ‐0.42 to ‐0.51 (Ps< 0.05, N=24). In MZs, non‐significant within‐twin pair correlations ranged from ‐0.31 to ‐0.36, (Ps= 0.11 – 0.16, N=21).ConclusionBy using case‐control twin design we showed that within twin pairs, a co‐twin with higher amyloid pathology had poorer episodic memory. Results suggest that amyloid‐EM relationship is evident when controlling for shared environmental and genetic effects, but studies with larger samples of MZ and DZ twins in different stages of AD continuum are warranted.
Associations between dietary spermidine intake, cognition and brain volumes
Authors: Tavares Juliana F , Landstra Elvire N , Brunner Julia , Boenniger Meta M , Lohner Valerie , Conrad Johanna , Nöthlings Ute , Breteler Monique MB 
Published: December 2020

AbstractBackgroundSpermidine is the most abundant polyamine in the human body, but its intracellular concentrations decrease with ageing. Spermidine supplementation reportedly protected against age‐related changes in cognition and brain structures in fruit flies (Gupta et al, 2013), and increased memory performance in older human adults (Wirth et al, 2018). However, the effects of dietary spermidine intake on brain‐related outcomes are unclear. Therefore, we evaluated whether and how dietary spermidine is cross‐sectionally associated with cognitive function and brain structures in a population‐based sample.MethodsWe based our analyses on participants from the Rhineland study with complete nutritional and cognitive assessment (n=2906, age 54.8±13.5 years), and with complete nutritional assessment and T1‐MRI scans (n=2264, age 54.1±13.4 years). Habitual dietary spermidine intake was estimated through a validated food frequency questionnaire. Cognitive performance was measured using eight cognitive tests that assessed performance in multiple domains (processing speed, executive functions, working and episodic verbal memory). These domains were summarized using z‐score averaging, producing a global cognitive function score. Brain volumetric measures (total brain, white and grey matter, cortex and hippocampus) were obtained using Freesurfer (Fischl et al, 2002). We quantified the relation between spermidine intake and the outcomes with multivariate linear models adjusted for age, sex and education. For brain volumes, models were additionally adjusted for estimated total intracranial volume.ResultsThe mean dietary intake of spermidine was 55.1±21.4 μmol/day. Higher spermidine intake (per SD increase) was associated with better global cognitive performance (ß=0.02, 95%CI=0.001 ‐ 0.03), and processing speed (ß=0.03, 95%CI=0.004 ‐ 0.05) and episodic verbal memory (ß=0.03, 95%CI=0.001 ‐ 0.06) domains. Conversely, dietary spermidine intake was not or inversely associated with brain volumetric measures (cortex: ß =‐0.91, 95%CI=‐1.82 – ‐0.02; left hippocampus: ß =‐0.01, 95%CI=‐0.03 – ‐0.002).ConclusionsOur results confirmed a positive association between dietary spermidine intake and better global cognitive function. However, we also found higher dietary spermidine intake to be associated with smaller cortical and left hippocampal volume. These seemingly contradictory results underscore the need for further research to better understand the effects of spermidine in cognition and brain related outcomes as well as the biological mechanisms underlying these associations.
Plasma amyloid‐β oligomerization assay as a screening test for abnormal amyloid status
Authors: Mofrad Rosha Babapour , Scheltens Philip , An Seong Soo , Kang Sungmin , Kim SangYun , Van Berckel Bart N.M. , Visser Pieter Jelle , van Der Flier Wiesje , Teunissen Charlotte E. 
Published: December 2020

AbstractBackgroundThe dynamic process of amyloid‐β (Aβ) oligomerization is considered vital for the neurotoxic effects of Aβ in Alzheimer’s disease (AD). Measuring plasma Aβ oligomerization tendency (OAβ) in blood would provide a simple and low‐cost tool for AD diagnosis. Therefore, we assessed the performance of plasma OAβ as a marker for abnormal amyloid status. We additionally evaluated the effect of long‐term storage, as this may influence plasma OAβ levels.MethodWe included 414 subjects regardless of clinical diagnosis from the Amsterdam Dementia Cohort and European Medical Information Framework for AD project (table1). Amyloid status was determined by visual read on Positron Emission Tomography (PET). Plasma OAβ was measured using the Multimer Detection System (MDS). The effect of long‐term storage on plasma MDS‐OAβ was assessed using Generalized Linear Models (GLM) including storage period, amyloid status, and their 2‐way interaction. In case of a significant 2‐way interaction, the cohort was stratified based on the median storage‐period (4 years). Age and Apolipoprotein (APOE)e4 adjusted, plasma MDS‐OAβ levels were evaluated between normal and abnormal amyloid individuals using GLM. Associations between plasma MDS‐OAβ and Aβ‐PET status were assessed using logistic regression analyses and receiver operating characteristics analyses.ResultWe found a 2‐way interaction for amyloid status and storage period on plasma MDS‐OAβ levels. In samples stored ≤4 years, but not >4 years, plasma MDS‐OAβ was higher in abnormal Aβ‐PET individuals, and could identify abnormal amyloid status with an Area Under the Curve (AUC) of 74% (95%CI:67%‐81%). Combining APOEe4 and age with plasma MDS‐OAβ revealed an AUC of 81% (95%CI: 74%‐87%; figure 1), which performed better than age and APOEe4 genotype alone (AUC: 70%, 95% CI: 63‐78, p=0.01). Using the highest Youden cutoff (45, sensitivity=76%, specificity=69%) to identify 100 individuals with abnormal Aβ‐PET status reduced the number of PET scans by 118, and lowered PET costs from 1.490.000 to 900.000 USD (40%).ConclusionPlasma MDS‐OAβ together with APOEe4 and age, has the potential to identify brain amyloidosis. Additionally, plasma MDS‐OAβ as a screener could reduce the costs may reduce the number of PET scans needed to screen for amyloidosis, which is highly relevant for clinical trials.
Optimized regional analysis to detect longitudinal 18F‐RO‐948 tau PET change in early AD
Authors: Klein Gregory , Scott David , Leuzy Antoine , Smith Ruben , Jögi Jonas , Ohlsson Tomas , Stomrud Erik , Borroni Edilio , Hansson Oskar 
Published: December 2020

AbstractBackgroundAnalyses from the Swedish BioFINDER‐2 study have shown that tau burden change seen via 18F‐RO‐948 tau PET tracer replicates the post‐mortem spreading pattern of tau. The greatest longitudinal changes have thus far been seen in Braak regions I/II for amyloid positive (Aβ+) cognitively unimpaired (CU) subjects, and Braak regions III/IV and V/VI for Aβ+ subjects with mild cognitive impairment (MCI) and AD dementia, respectively. In the design of clinical trials, selecting a composite cortical region with the greatest longitudinal effect size (LES) is a key objective in keeping trial sample size practical. In this study, we employed a Lasso optimization method to determine a combination of brain subregions optimized for maximal effect size in the pre‐symptomatic and early AD populations.MethodStudy participants were scanned at baseline and a targeted first follow‐up scan at 12 months with 18F‐RO‐948 tau PET. Annualized change of tau burden for 116 subregions was computed using FreeSurfer v6.0 and an SUVR method with an inferior cerebellar grey reference region. Subjects were analysed separately based Aβ‐status (using CSF Aβ42/Aβ40) and baseline clinical diagnosis: CU, MCI and dementia due to AD. A Lasso optimization with 5‐fold cross validation was used to explore the optimum combination and weighting of ROIs to maximize LES.ResultLongitudinal scans from 14 Aβ+ CU subjects and 18 Aβ+ MCI were included in this analysis. Maximum LES via Lasso for the Aβ+ CU group was 1.01, and 0.81 for the Aβ+ MCI group. Both sets of composite ROIs included three subregions, listed as follows with decreased Lasso weighting: (left‐entorhinal, right‐amygdala, right‐hippocampus) for Aβ+ CU and (left‐fusiform, left‐temporal pole, right‐superiorparietal) for the Aβ+ MCI group. Lasso LES was larger than LES found with Braak staging ROIs: 0.87 for the Aβ+ CU group using Braak I/II, and 0.62 for the Aβ+ MCI group using Braak III/IV.ConclusionA Lasso method determined composite target ROIs with greater effect size than ROIs selected using Braak staging models. Little overlap exists in region sets optimized for pre‐symptomatic and early AD populations, indicating that careful endpoint design is required to detect change in longitudinal studies.