bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can plasma amyloid‐beta levels be considered as a potential biomarker to discriminate preclinical Alzheimer’s disease?
Authors: Wang Xiaoni , Jiang Jiehui , Han Ying 
Published: December 2020

AbstractBackgroundWe investigated plasma amyloid‐beta (Aβ) levels across Alzheimer’s spectrum from normal control (NC) to cognitive impairment (CI) vis preclinical AD (PreAD) as well as their association with central biomarkers to explore their potential as a pre‐screening tool for identifying early AD.MethodOne hundred and thirty‐nine participants (50 NC, 34 PreAD and 55 CI) from SILCODE project and memory clinic in Xuanwu Hospital were included. Preclinical AD patients were defined as cognitively normal subjects with positive amyloid‐PET. Cognitive impairment patients were defined as objective cognitive impairment due to AD. Plasma Aβ40 and Aβ42 were measured using Meso Scale Discovery technology. Analysis of covariance (ANCOVA) was used to examine the plasma Aβ levels across the three groups. A general linear model analysis was used to test for association between plasma Aβ levels and amyloid burden, gray matter volume (GM) and amplitude of low frequency fluctuation (ALFF). Further, mediating effect of amyloid burden on association between plasma Aβ levels and neurodegeneration biomarkers were tested.ResultThe levels of plasma Aβ42/Aβ40 and Aβ42 levels were different among three groups (for Aβ42 [pg/ml]: 12.27(4.35) in NC, 10.93(3.00) in PreAD, and 10.08(2.73) in CI [P=.045 adjusted for carrier of ApoE ε4 allele, age, sex, and education]; for Aβ42/Aβ40: 0.017(0.005) in NC, 0.014(0.003) in PreAD, and 0.013(0.004) in CI [P <. 001]) (Figure 1). Globally, Plasma Aβ42 and Aβ42/Aβ40 ratio negatively correlated with global SUVR (p=0.007 and p=0.001) and positively correlated with gray matter volume (p=0.011 and p<0.001). Plasma Aβ40 showed significantly positive correlation with ALFF (p=0.008) and Aβ42/Aβ40 ratio showed an opposite correlation with ALFF (p=0.019) (Figure 2). Global SUVR significantly mediates the relationship between plasma Aβ42/Aβ40 ratio and gray matter volume (average causal mediation effects 95%CI: 13.912‐86.439).ConclusionThe present data show plasma Aβ42/Aβ40 ratio were lower in patients with cognitive impairment than preclinical AD than normal controls. Plasma Aβ were correlated with brain amyloid deposition, structural atrophy and functional alteration. These results suggest the potential for plasma Aβ serving as a more cost‐effective prescreening tool in clinical practice.
Season of birth and the risk of dementia in the general population: A long‐term, prospective cohort study
Authors: Mooldijk Sanne S , Licher Silvan , Vinke Elisabeth J , Vernooij Meike W , Ikram M. Kamran , Ikram M. Arfan 
Published: December 2020

AbstractBackgroundEnvironmental exposures early in life are important for shaping brain development. Season of birth as a proxy for these exposures has been associated with the risk of brain diseases in adolescence and mid‐life, such as schizophrenia and depression. We investigated the link between season of birth and risk of dementia. We further explored underlying structural pathways by studying the link with brain changes on MRI.MethodWithin the Dutch prospective population‐based Rotterdam Study, we assessed dementia incidence in 12,964 persons born between 1887 and 1960. We used Cox proportional hazard models to determine the relationship between season of birth with incident dementia, and Alzheimer’s disease (AD), with summer births as reference. In addition, we compared dementia incidence among participants born in a cold winter compared to those born in a normal winter. All models were adjusted for age and sex, and additionally for education, ethnicity, income, APOE‐ε4 genotype, cardiovascular risk factors and depressive symptoms. Furthermore, we examined the association between season of birth with volumetric and microstructural integrity markers on brain MRI in 5,436 dementia‐free participants.ResultDuring 26 years of follow up, 1,633 participants developed dementia, of whom 1,282 had AD. The risk of dementia in both winter and fall born participants was higher than those born in summer (Figure 1, age and sex adjusted hazard ratio (HR) 1.14 [95% confidence interval (CI) 1.00‐1.40] and 1.17 [1.02‐1.34], respectively), with stronger effect sizes for AD (1.24 [1.06‐1.45] and 1.23 [1.05‐1.45], respectively). In addition, we found a higher risk for participants born in a cold or very cold winter HR 1.08 [0.88‐1.34] and 1.14 [0.87‐1.48], respectively, compared to those born in a normal winter. Further adjustment did not change these associations. We did not find an association between season of birth and any of the brain imaging markers measured in late life.ConclusionIn this western European population of community‐dwelling individuals, winter and fall births are associated with a higher incidence of dementia, especially of AD. We did not find evidence for changes in structural and microstructural brain markers as an underlying mechanism.
Impact of bioinformatic pipelines and reference databases on 16S rRNA gene sequencing in patients with cognitive impairment
Authors: Marizzoni Moira , Gurry Thomas , Lopizzo Nicola , Salvatore Marco , Franzese Monica , Mirabelli Peppino , Frisoni Giovanni B , Cattaneo Annamaria 
Published: December 2020

AbstractBackground
Sequencing of 16S ribosomal RNA (rRNA) gene is the most used technique for the identification of Alzheimer’s specific differences in the relative abundance of specific organisms. Several bioinformatic pipelines have been developed so far to characterize complex gut microbial communities. This study aims at evaluating the effect of bioinformatic pipelines and reference databases on the taxonomic classification of bacteria in the stools of patients with cognitive impairment.MethodDNA from frozen stool samples of 40 subjects was extracted using QIAamp Fast DNA stool kit after mechanical disruption (bead‐beating) and amplified using primers targeting the V3‐V4 region of the bacterial 16S rRNA gene. Sequencing was performed according to the 16S‐protocol on MiSeq (Illumina). Sequence read files were analysed using 4 commonly used pipelines run on a Linux workstation: QIIME2 (Bokulich, Microbiome, 2018), Bioconductor (Callahan, F1000Research 2016, version 29 oct 2018), UPARSE (Edgar, Nat Methods, 2013) and mothur (Kozich, Applied and Environmental Microbiology, 2013). SILVA 132 and RDP v16 reference databases were used in all analyses. For UPARSE and mothur, sequences were clustered into OTUs at 99% identity threshold. Differences of relative abundances of phyla and genera were evaluated across pipelines using Friedman rank sum test.ResultThe identification of phyla but not their quantification was consistent among all the pipelines using both databases (p<0.001). At genus level, all pipelines identified Bacteroidetes, Alistipes, Faecalibacterium and Ruminococcus as the most abundant genera, regardless of the database applied for taxonomic assignment. Again, their relative abundance was different across pipelines and databases (p<0.001).ConclusionThe comparison between different studies should take analytical pipeline and database used for taxonomic assignation into account. To overcome these limitations, the scientific community should quickly converge towards a consensus pipeline for guarantee research reproducibility.
Characterization of monomeric and soluble aggregated Aβ in Down’s syndrome and Alzheimer’s disease brains
Authors: Gkanatsiou Eleni , Sahlin Charlotte , Portelius Erik , Johannesson Malin , Söderberg Linda , Fälting Johanna , Basun Hans , Möller Christer , Odergren Tomas , Zetterberg Henrik , Blennow Kaj , Lannfelt Lars , Brinkmalm Gunnar 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is the most common form of dementia and is characterized by the two hallmarks, amyloid plaques and neurofibrillary tangles in the brain. The plaques consist of aggregated beta amyloid (Aβ) peptides, formed by proteolytic cleavages of amyloid precursor protein (APP). Down’s syndrome (DS) is a genetic disease with an extra copy of chromosome 21, harbouring the APP gene. DS individuals are at increased risk to develop amyloid pathology. Most DS have substantial amyloid pathology at their 40s, with clinical signs of deterioration before the age of 60. Our aim was to compare the Aβ peptide pattern in DS and AD brains, to better understand the difference between them.MethodsImmunoprecipitation (IP) in combination with mass spectrometry was used to identify both soluble and insoluble Aβ peptides, as well as to characterise the composition of Aβ oligomers/protofibrils. Two different antibody combinations were used; 6E10+4G8 to identify total Aβ peptide contents and the Aβ protofibril selective antibody mAb158 to identify the Aβ peptides present in oligomers/protofibrils. Before IP, cortical tissue from patients with DS (with amyloid pathology), sporadic AD and controls were homogenized and fractionated into TBS (TBS soluble) and formic acid (insoluble) fractions.ResultsFrom IP with 6E10+4G8 several truncated Aβ peptides were identified in all groups, including: 1‐X, 2‐X, 3‐X, 4‐X, 5‐X, 11‐X and –X to 15 as well as post‐translationally modified peptides with oxidation and pyroglutamation. Similarities were observed when comparing the Aβ peptide processing in AD and DS, with the exception of –X to 15 Aβ peptides for which the pattern is different. By using mAb158, Aβ1‐40, Aβ1‐42 and Aβ4‐42 were identified. Higher relative AβX‐42 signals were obtained compared to samples IP’d with 6E10+4G8, indicating that the protofibrils/oligomers were enriched with peptides ending at aa42.ConclusionAll Aβ peptides found in AD are also present in DS (with amyloid pathology) indicating a generally similar pathway of Aβ peptide production, apart from –X to 15. Likewise, the Aβ peptides forming protofibrils/oligomers in both AD and DS were similar, implying the possibility to exploit the potential utility of a treatment with clinical benefit in sporadic AD for subjects with DS.
Plasma phospho‐tau217 is a potential early diagnostic and prognostic biomarker of Alzheimer’s disease
Authors: Janelidze Shorena , Mattsson Niklas , Smith Ruben , Stomrud Erik , Palmqvist Sebastian , Dage Jeffrey L. , Hansson Oskar 
Published: December 2020

AbstractBackgroundThere is an urgent need for inexpensive and minimally invasive blood biomarkers of Alzheimer’s disease (AD) that could be used to detect early disease changes.MethodWe measured plasma levels of tau phosphorylated at threonine 217 (P‐tau217) in the prospective Swedish BioFINDER (BF) I and II studies (n=1057). BF‐II included cognitively unimpaired individuals (CU, n=275) and patients with mild cognitive impairment (MCI, n=161), AD dementia (n=114) and non‐AD neurodegenerative diseases (n=91) who underwent tau‐PET imaging using [18F]RO948. A subcohort of 157 participants had two or three tau‐PET scans on average 1.0 years apart (range 0.1‐1.6 years). In BF‐I, 264 CU and 152 MCI were followed longitudinally with clinical examinations to determine conversion to AD dementia (mean follow‐up 4.9 years, range 1.0‐8.6 years).ResultPlasma P‐tau217 levels were increased in CU individuals with abnormal amyloid‐β (Aβ)‐PET but still normal tau‐PET in the earliest Braak I‐II (entorhinal) ROI (Aβ‐PETpos/tau‐PETneg group vs Aβ‐PETneg/tau‐PETneg group, p<0.001). Furthermore, when testing the relation to global Aβ load in non‐linear spline models (Figure 1), we found that plasma P‐tau217 started to increase at Aβ‐PET SUVR of 0.39, which preceded the increase in tau‐PET measures (Aβ‐PET SUVR 0.42‐0.62). In line with these data, the majority of cases that were discordant for plasma P‐tau217 and tau‐PET in Braak I‐II were positive for P‐tau217 and negative for tau‐PET (P‐tau217pos/tau‐PETneg, n=68 [72%] and P‐tau217neg/tau‐PETpos, n=27 [ 28%]). Among participants with normal baseline tau‐PET, the rates of longitudinal increase in tau‐PET in the Braak I‐II ROI were higher in cases with abnormal plasma the P‐tau217 at baseline (p=0.017). Finally, in non‐demented individuals, abnormal levels of P‐tau217 were associated with increased risk of future AD dementia (hazard ratio 5.4; 95% confidence interval 3.5‐8.4; p<0.001).ConclusionPlasma P‐tau217 levels increase in early stages of AD when insoluble tau aggregates are not yet detectable by tau‐PET and predict both subsequent increase in tau‐PET as well as conversion to AD dementia. Plasma p‐tau217 holds promise as a marker for early AD‐pathology.
Plasma carotenoids and medial temporal lobe atrophy in older adults
Authors: Thomas Aline , Proust‐Lima Cécile , Baillet Marion , Helmer Catherine , Delcourt Cécile , Foubert‐Samier Alexandra , Catheline Gwenaelle , Féart Catherine , Samieri Cécilia 
Published: December 2020

AbstractBackgroundCarotenoids are vegetable pigments uniquely provided by diet which have antioxidant, immunomodulatory and specific neuroprotective properties. Carotenes (found in orange‐yellow fruits and vegetables) are precursors of retinoids, key signaling molecules for synaptic plasticity. The xanthophylls, lutein and zeaxanthin (found in green vegetables, orange‐yellow fruits and corn) cross the blood‐brain barrier, may decrease lipid peroxidation and stabilize lipid‐protein structures in neuronal membranes. Limited epidemiological studies on dietary carotenoids (assessed by questionnaires) reported inconsistent associations with brain aging using cognitive change as an outcome (and not neuroimaging or clinical dementia or Alzheimer’s disease diagnosis). However, blood carotenoids levels were associated with lower risk of dementia over 10 years, in a large cohort of older adults, the Three‐City (3C) study. Here, we further investigated whether blood carotenoids were also associated with the 10‐year atrophy of the medial temporal lobe (MTL), a central biomarker of neurodegeneration in aging.MethodWe included 461 dementia‐free participants from the 3C study (age ≥65), who had plasma carotenoid (α and β‐carotene, lycopene, lutein, zeaxanthin, β‐cryptoxanthin) measures at baseline and who underwent at least one of the three repeated brain imaging exams performed in the subsequent 10 years. Linear mixed models were used to assess the association between plasma carotenoids and MTL volume change assessed using FreeSurfer 5.1 segmentation software.ResultOver a median follow‐up of 5.1 years (maximum 11.8 years), higher plasma levels of total carotenoids and of β‐carotene were associated with lower decline in MTL volume (P = .04 and P = .008, respectively). The mean differences in MTL volume change for each increase of 1 SD were 0.02 (95% CI, 0.001; 0.04) cm3/year and 0.02 (0.01; 0.04) cm3/year for total carotenoids and β‐carotene, respectively. Other carotenoids were not significantly associated with MTL atrophy.ConclusionThe associations found between plasma total carotenoids and β‐carotene and 10‐year atrophy of the MTL in this large cohort of older adults suggest a beneficial role of carotenoids for the prevention of age‐related neurodegeneration.
Usefulness of cognitive training program using virtual reality and mixed reality
Authors: Park So‐Hee , Baek Joon Hyun , Lee SangHoon , Kang Seung Wan , Jang Jun Seok , Na Hae Ri 
Published: December 2020

AbstractBackgroundNowadays virtual reality (VR) and mixed reality (MR) is used as a psychological and occupational therapeutic option to the patients of depression, phobia, post traumatic stress disorder and stroke patients. VR and MR have a number of advantages because it is entertaining, thus motivating the patient. Therefore VR and MR can be used for cognitive therapy to the elderly cognitive declined people because it can give attention, motivation and stimulation to them. Our previous pilot study showed that cognitive training program using VR and MR improved cognitive function, depressive mood and electrophysiologic brain activity on Mild cognitive impairment (MCI) patients. This is the extensive study to show the usefulness of VR and MR using cognitive training on MCI patients, which added more session, program and enrolled more patient in comparison with previous pilot study.MethodThis study was an 8‐week, single‐blind study of 20 patients with MCI. The cognitive training program included art therapy, aerobic exercises, memory training, including face‐name association, object recall training, and spaced retrieval; visuo‐motor organization using software; similarity and ruled based categorization; and behavior modification and sequencing (e.g., making change, paying bills) using VR and MR and computerized program. Neuropsychological function was assessed using K‐MMSE (Korean Mini‐Mental State Examination), Clinical dementia rating(CDR), Alzheimer`s Disease Assessment Scale‐Cognition(ADAS‐cog), Korean version of short form Geriatric Depression Scale(SGDS‐K) and Neuropsychiatric Inventory(NPI). Quantitative electroencephalogram (EEG) was assessed on cognitive training days before treatment and after each treatment phase. Then EEG was analyzed by using “iSyncbrain” which is cloud‐based, AI‐driven EEG analysis platform.ResultAfter two months (8 sessions) of treatment, cognitive function, neuropsychiatric symptoms and depression, which were assessed by using MMSE, NPI and SGDS respectively, showed significant improvements (p<0.05). Also there were significant increase of the EEG alpha/theta ratio on both dorsolateral prefrontal cortex and right parietal cortex, which may imply improvement of frontal and visuospatial function. However, there were no statistically significant differences except Source ROI Power and connectivity.ConclusionCognitive training program using VR and MR showed improvement of cognitive function, depressive mood and electrophysiologic brain activity.
Preliminary validation of the Brief Assessment of Impaired Cognition (BASIC) and the Brief Assessment of Impaired Cognition Questionnaire (BASIC‐Q) for identification of mild cognitive impairment
Authors: Jørgensen Kasper , Nielsen Rune , Nielsen Ann , Waldorff Frans Boch , Waldemar Gunhild 
Published: December 2020

AbstractBackgroundThe aim of this study was to perform a preliminary validation of the Brief Assessment of Impaired Cognition (BASIC)1 and the Brief Assessment of Impaired Cognition Questionnaire (BASIC‐Q)2 for identification of mild cognitive impairment (MCI).MethodA total of 163 socio‐demographically matched patients (MCI, n = 42, and dementia, n = 121) and control participants (n = 83) were included in the study. BASIC includes the components: self‐report, informant report, and two brief cognitive tests, whereas BASIC‐Q includes the components: self‐report, informant report, and orientation. BASIC takes about 5 minutes to administer and BASIC‐Q a little less.ResultA high discriminative validity for MCI versus control participants was found for both BASIC (sensitivity 0.85, specificity 0.89) and BASIC‐Q (sensitivity 0.88, specificity 0.88). In comparison, the MMSE had low sensitivity (0.61) and moderate specificity (0.72). All components of BASIC and BASIC‐Q contributed significantly to differentiate MCI from control participants. The components of BASIC and BASIC‐Q also contributed significantly to differentiate MCI from dementia except for self‐report, which was identical in the two groups.ConclusionThe results indicate that BASIC and BASIC‐Q are equally efficient and valid instruments for identification of MCI in a memory clinic setting. Self‐report and informant report are equally valid measures of cognitive impairment early in the process of decline, but as dementia sets in the validity of self‐report becomes inferior to informant report, possibly reflecting loss of insight. In contrast, the validity of informant report seems to increase with the progression of cognitive impairment. Further studies are warranted to replicate and expand on these findings. References: 1. Jorgensen K, Nielsen TR, Nielsen A, Waldorff FB, Hogh P, Jakobsen S, et al. Brief Assessment of Impaired Cognition (BASIC)‐Validation of a new dementia case‐finding instrument integrating cognitive assessment with patient and informant report. Int J Geriatr Psychiatry. 2019;34(11):1724‐33. 2. Jorgensen K, Nielsen TR, Nielsen A, Waldorff FB, Waldemar G. Brief Assessment of Impaired Cognition Questionnaire (BASIC‐Q) – development and validation of a new tool for identification of cognitive impairment in community settings (submitted for publication). 2019.
Patients’ versus caregivers’ reports of quality of life in elderly patients with cognitive impairment
Authors: Shin Il‐Seon , Kim Sung‐Wan , Kim Jae‐Min 
Published: December 2020

AbstractBackgroundA few studies have examined the differences between patient and caregiver reported Quality of Life (QOL) in patients with dementia. The purpose of this study was to investigate the differences between patient and caregiver ratings on QOL in elderly patients with cognitive impairment and assessed the relationship of patient QOL and cognitive function, and depression.MethodForty‐seven elderly patients with cognitive impairment and their caregivers participated. Patient QOL was assessed using by the Korean version of Quality of Life‐Alzheimer's Disease (KQOL‐AD) scale. Each patient and caregiver rated the patient QOL. Korean Mini Mental Status Exam in the Korean version of the CERAD assessment packet(MMSE‐KC) and Short form of the Geriatric Depression Scale(SGDS) were also assessed.ResultThere were no significant differences between patient and caregiver ratings on all QOL items except marriage. There were significant correlations between patient and caregiver reports of patient on all QOL items except marriage and total KQOL‐AD scores. Total KQOL‐AD Scores of patient QOL were positively significant correlated with MMSE‐KC scores and were negatively significant correlated with SGDS scores.ConclusionPatient and caregiver reported QOL in elderly patients with cognitive impairment did not differ. Elderly patients seem to be able to assess their own QOL properly although they have impairment in cognitive function. Depression of elderly patients with cognitive impairment adversely affects patient QOL.
Cognitive evolution of Alzheimer’s disease patients according to the serverity of obstructive sleep apnea
Authors: Carnes Anna , Piñol Gerard , Dakterzada Faride , Targa Adriano , Benitez Ivan David , Huerto Raquel , Barbe Ferran 
Published: December 2020

AbstractBackgroundTo investigate the effect of OSA on the cognitive evolution of patients with AD.MethodIn this prospective, single‐center study (NCT02814045), patients with mild‐moderate AD with and without untreated OSA were evaluated at the baseline and after 12, 24 and 36 months of follow‐up. OSA was defined as an apnea‐hypopnea index (AHI) >15/h. The primary outcome was measured by the cognitive scores on the Alzheimer’s Disease Assessment Scale‐Cognitive subscale (ADAS‐cog) and Mini‐Mental State Examination (MMSE).ResultThe cohort included 146 patients with 125 validated PSGs, from which 40 patients were diagnosed as non‐OSA (32%) and 85 as OSA (68%). The median [IQR] age of the eligible individuals was 75.0 [72.0;80.0] years and the majority was composed of women (57.25%). In addition, the mean (SD) MMSE score at the baseline was 23.53 (2.23). In the ADAS‐cog score, the mean (SD) change at the 12 months of follow‐up was 2.97 (5.73) and 0.29 (5.65) for the non‐OSA and OSA group, respectively. The estimated mean (95%) difference between the groups was ‐2.76 (0.12 to 0.16) (p=0.033). No cognitive changes were observed at several cognitive domains evaluated. There was a cognitive decline along the 3 years of follow‐up according to the MMSE score (p<0.001) (Figure 1), but no differences between the groups were observed.ConclusionOSA was not associated with a worse cognitive evolution after 36 months of follow‐up. Further studies will be necessary to improve the understanding of the OSA impact on the cognitive evolution of AD patients.