bluuebunny/crossref_metadata_2025_split huggingface dataset:
QEEG: The tentative biomarker for early screening of preclinical Alzheimer’s disease or progressiveness of subjective cognitive decline
Authors: Ho SeongHee , Yang Dong Won , Hong Yun Jeong , Jeong Jee Hyang , Park Kee Hyung , Kim SangYun , Wang Minjung , Choi Seong Hye , Han SeungHyun , Kang Seung Wan , Lee Hannah , Kim Seon Myeong 
Published: December 2020

AbstractBackgroundEarly screening biomarker has been required to discriminate higher risk of progressive subgroup in subjective cognitive decline(SCD) at preclinical stage. Study purpose was to identify quantitative EEG patterns among different condition of amnestic SCDMethodFrom 6 dementia clinics in Korea, we enrolled participants aged over 60 years with complaining of persistent cognitive decline, performance range of 7% to 50% of the verbal memory tests and over 7% of the rest subtests of comprehensive neuropsychological battery. Both 18F‐Florbetaben brain amyloid‐beta PET and genetic test for APOE ε4 allele were conducted. EEG was measured at 19 channels of international 10‐20 system under resting state, and spectrum power and power ratio were calculated. Source cortical activity was mathematically estimated by standardized low resolution brain electromagnetic tomography(sLORETA)Result120 SCD subjects (male 53, female 67) were included. Amyloid PET(+) was 25 (20.8%) and APOE ε4 allele (+) was 26(21.6%) independently. Amyloid PET (+) SCD had higher frequency of APOE e4 (48%) compared to amyloid PET (‐) SCD (14%). We selected 67 amyloid PET (‐) SCD older than 65 years to escape age differences between 2 groups. Amyloid PET (+) SCD showed significant increase of relative theta power at left frontotemporal(Fp1, F7, T5), both occipital(O1,2) and right parietal(P4) channels. Similarly, significant enhancement of theta was observed at left superior and transverse temporal, fusiform and cuneus at sLORETA in amyloid PET (+) SCD. Among amyloid PET (+) SCD, APOE ε4 (+) subgroup showed significant increase of theta/beta ratio at both superior frontal and anterior cingulate, right parietal and occipital areaConclusionAmnestic SCD with amyloid (+) showed relative enhancement of slow wave in resting EEG, which have been similarly reported about amnestic MCI or AD dementia. QEEG could be tentative biomarker to screen AD or to predict progressiveness of SCD at preclinical stage. Longitudinal study and development of single quantitative index of QEEG to evaluate individual subject will be needed to confirm its clinical significance.
Effectiveness of lifestyle and psychosocial interventions in reducing cognitive decline in older people: Systematic review
Authors: Mansour Hassan , Whitty Emma , Aguirre Elisa , Palomo Marina , Charlesworth Georgina , Ramjee Serena , Poppe Michaela , Brodaty Henry , Kales Helen C , Morgan‐Trimmer Sarah , Nyman Samuel , Lang Iain A , Walters Kate , Petersen Irene , Wenborn Jennifer , Minihane Anne‐Maire , Ritchie Karen , Huntley Jonathan D , Walker Zuzana , Cooper Claudia 
Published: December 2020

AbstractBackgroundObservational findings suggest that a third of dementia cases are attributable to modifiable risk factors (Livingston et al, 2017). However, we are still unclear on what non‐pharmacological interventions should look like or what a manualised dementia prevention programme might include.MethodPubMed, EMBASE (Ovid), PsycINFO, CINAHL, Web of Science, and reference lists of included studies were systematically searched and screened by two independent reviewers. We included lifestyle and psychosocial interventions that aimed to reduce cognitive decline in healthy people aged 50+, and people of any age with Subjective Cognitive Decline or Mild Cognitive Impairment. We narratively synthesised evidence, prioritising results from studies rated at lower Risk of Bias (ROB) and used Centre for Evidence Based Medicine guidelines to grade levels of evidence. These findings were used to inform co‐production of an internationally collaborated APPLE‐Tree (Active Prevention in People at risk of dementia: Lifestyle, bEhaviour change and Technology to REducE cognitive and functional decline) programme.ResultA total of 64 studies were included describing psychosocial (n=12), multi‐domain (n=10), exercise (n=36) and dietary (n=6) interventions. We found Grade A evidence that 4+ months of aerobic exercise twice weekly had a moderate effect on global cognition. With interventions that integrate, cognitive and motor challenges (e.ge. dance or dumb bell training) had small to moderate effects on memory or global cognition. We also found Grade B evidence that 4+ months of creative art or storytelling groups; 6 months of resistance training and a two‐year, dietary, exercise, cognitive training and social intervention had small but positive effect on global cognition. Conflicting evidence was observed for interventions solely focusing on increasing Mediterranean diet adherence. With effects for some interventions remaining up to a year beyond facilitated sessions. Only two lower ROB studies measured impact of non‐pharmacological interventions onto dementia incidence with neither finding significant effects.ConclusionBased on current published findings an evidence‐based intervention strategy to improve global cognition, memory and executive functioning should include group therapy carried out for 4+ months, promoting engagement in regular (at least weekly) activity, involving aerobic or resistance exercise, and cognitively demanding (visuospatial/memory) or creative tasks.
Long‐term treatment with cholinesterase inhibitors in Alzheimer's disease is associated with modest but persisting benefits on cognition and reduced mortality
Authors: Eriksdotter Maria , Xu Hong , Jönsson Linus , Wimo Anders , Nordström Peter , Garcia‐Ptacek Sara 
Published: December 2020

AbstractBackgroundCholinesterase inhibitors (ChEIs) are the mainstay treatment of Alzheimer’s dementia (AD) and are considered symptomatic. However, their long‐term effectiveness is not well studied. This study aims to investigate whether ChEIs are associated with less cognitive decline in AD, and decreased risk of severe dementia or death.MethodAD patients from the Swedish Dementia Registry (SveDem) starting on ChEIs within three months of the dementia diagnosis were included and compared to non‐treated AD patients. In a propensity score matched cohort, the association between ChEI use and cognitive trajectories assessed by MMSE scores were examined with a mixed model, and severe dementia (MMSE<10) or death as outcomes with Cox proportional hazards models.ResultThe matched cohort included 11,652 ChEI‐users and 5,826 non‐users. ChEI use was associated with higher MMSE at each visit (0.13 MMSE points/year; 95% confidence interval‐CI 0.06, 0.20). Moreover, ChEI users had a 27% lower risk of death (0.73; CI 0.69, 0.77) compared with non‐users. Galantamine was associated with lower risk of death (0.71; CI 0.65, 0.76), lower risk of severe dementia (0.69; CI 0.47‐1.00), and had the strongest effect on cognitive decline of all the ChEIs (0.18 MMSE points/year, CI 0.07, 0.28).ConclusionChEIs are associated with cognitive benefits which are modest but persist over time. An association with reduced mortality partly explained by their cognitive effects was found. A significant reduction in the risk of developing severe dementia was demonstrated by the ChEI galantamine.
Gray matter atrophy, but not vascular brain injury is related to cognitive impairment in patients with heart failure
Authors: Leeuwis Anna E. , Amier Raquel P. , Marcks Nick , Nijveldt Robin , Hooghiemstra Astrid M. , Rocca Hans‐Peter Brunner‐La , Roos Albert , de Bresser Jeroen , Bron Esther E. , Niessen Wiro J. , Buijs Mathijs , Barkhof Frederik , van Rossum Albert , van Der Flier Wiesje ,   Heart‐Brain Connection Consortium
Published: December 2020

AbstractBackgroundCognitive impairment in heart failure (HF) interferes with the capacity to self‐care and is associated with adverse health outcomes. This underlines the importance of detecting the extent and nature of cognitive impairment in HF. We report on the presence and mutual association of neuroimaging markers and cognitive impairment in patients with HF.MethodWe included 147 patients with HF (69±10yrs; 32%F; MMSE 29±1) and 121 reference participants (66±8yrs; 46%F; MMSE 29±1) from the Dutch multicenter Heart‐Brain study. Brain MRI scans were rated for (lacunar) infarcts and microbleeds. Total grey and white matter volume, hippocampal volume and white matter hyperintensity (WMH) volume were calculated. We used a standardized neuropsychological test battery to measure cognition and calculated compound z‐scores for each cognitive domain. Associations between neuroimaging markers and cognitive functioning were investigated using linear regression analyses, with separate models for each cognitive domain. We adjusted for participant group, age, sex and education. To investigate whether associations differed according to participant group, interaction terms were included in our analyses.ResultPatients with HF had lower total grey matter volume and more vascular brain injury compared to the reference group, including WMH (median (interquartile range) 1.7(40) versus 0.6(1.8), p<0.001), (sub‐)cortical infarcts (13% versus 3%, p<0.01) and lacunar infarcts (28% versus 10%, p<0.001). Cognitive impairment was found in 18% of HF, most often in the domains of memory and attention/psychomotor speed. Overall, we found associations between smaller total grey matter volume and worse global cognition, more cortical and lacunar infarcts (standardized beta [stβ]=‐0.14‐0.56, p<0.05). Stratification for participant group showed associations between worse global cognition and smaller total (stβ=0.43, p<0.01) and hippocampal (stβ=0.22, p<0.05) grey matter volumes in HF. We found no association between cognition and vascular brain injury.ConclusionPatients with HF exhibit cognitive deficits more pronounced in the domains of memory and attention/psychomotor speed. Grey matter atrophy, but not vascular brain injury seems to be related to cognitive impairment in HF.
Predicting factors of cognitive progression in preclinical AD: A five‐year follow‐up of the insight‐study
Authors: Bombois Stephanie , Villain Nicolas , Genthon Remy , Younsi Nadjia , Levy Marcel , Houot Marion , Colliot Olivier , Lamari Foudil , Epelbaum Stéphane , Habert Marie‐Odile , Dubois Bruno 
Published: December 2020

AbstractBackgroundAs not all the asymptomatic Alzheimer Disease (AD) subjects will progress to symptomatic stages, targeting those individuals at high risk of progression to prodromal AD is relevant, especially for disease‐modifier therapeutic trials. The aim of this study is to determine markers of progression to prodromal AD in cognitively normal individuals.MethodINSIGHT‐preAD study is a cohort of 318 cognitively normal individuals, over 70 years, with subjective memory complaints, followed‐up for 5 years. Subjects were stratified by brain amyloid status (A(+) or A(‐)) according to the uptake of 18F‐Florbetapir. Demographic, cognitive, ApoE status and imaging (MRI and FDG‐PET) were performed at baseline. Clinical and cognitive assessments were repeated every 6 months, MRI, FDG‐PET and amyloid‐PET scans every 2 years. Definition of progressors: MMSE and FCSRT scores below the threshold for inclusion in the study was indicative of a possible progression to prodromal AD. An independent and blinded committee using adjudicated prodromal AD using the IWG‐2 criteria. Statistical analysis: Comparisons between A(+) progressors and A(+) non‐progressors were performed using Wilcoxon test for continuous variables and Fisher’s exact tests for qualitative variables.ResultAfter 5 years, 13 subjects progress to a mild cognitive impairment: 12 prodromal AD (11 typical phenotype; 1 atypical phenotype with a logopenic presentation) and 1 with a Lewy body phenotype. All the progressors were A(+), with a rate of progression of 14% among A(+) individuals. When compared to A(+) non‐progressors, the progressors had lower performance in each FCRST sub‐scores, lower total hippocampal volume (Median [Q1, Q3]: 2.43 [2.24, 2.56] versus 2.65 [2.45, 2.87]) and higher AV45 SUVr (1.23 [0.99, 1.32] versus 0.95 [0.84, 1.10], for a threshold of 0.79).ConclusionAs expected, the predicting factors from cognitively normal individuals to prodromal AD are the co‐occurrence of amyloid burden and tau pathology (represented by hippocampal volume loss and memory deficit). However, only 14% of A(+) subjects progress to prodromal AD after 5 years follow‐up. This result suggests protective and compensatory mechanisms that should be investigated to open up to innovative treatment.
Automatic detection of Alzheimer’s disease and mild cognitive impairment from spontaneous speech collected during tablet‐based interviews: A preliminary result
Authors: Shinkawa Kaoru , Kosugi Akihiro , Kobayashi Masatomo , Nishimura Masafumi , Nemoto Miyuki , Tsukada Eriko , Ota Miho , Nemoto Kiyotaka , Arai Tetsuaki , Yamada Yasunori 
Published: December 2020

AbstractBackgroundAs the world’s elderly population increases, health monitoring technologies that can automatically detect subtle changes resulting from Alzheimer’s disease (AD) have become increasingly important. In this respect, speech is one of the promising clues due to the expansion of voice‐based interaction systems such as smartphones and tablets. Indeed, previous studies have succeeded in quantifying language dysfunctions and identifying AD and mild cognitive impairment (MCI) from speech data collected during neuropsychological tests conducted by clinicians. Conducting such assessments in an automated fashion by using computer devices would extend opportunities for assessments and help with the early detection of AD. In particular, if we can detect language dysfunctions related to AD from various types of speech data (e.g., question answering and daily conversations), it would extend the scope of application and help improve the current worldwide low‐diagnosis coverage.MethodIn this study, we developed a tablet‐based application and collected spontaneous speech data during interview tasks from 106 Japanese seniors consisting of 48 healthy controls (HC), 33 MCI, and 25 AD.Participants answered nine questions relating to their current condition, yesterday’s dinner, games played as a child, and future travel plans. For comparison, we also collected speech data during neuropsychological tests (e.g., verbal fluency and picture description tasks) using the tablet. We extracted vocal and prosodic features from both speech data and then built binary classification models for differentiating MCI or AD from HC using a support vector machine with a feature selection method. We evaluated the models by leave‐one‐subject‐out cross‐validation.ResultWe found that the models using speech data during neuropsychological tests achieved the accuracy of 86.3% for HC vs. AD and 80.2% for HC vs. MCI. The models using spontaneous speech data from interview tasks achieved comparable accuracies: 87.7% for HC vs. AD and 81.6% for HC vs. MCI.ConclusionWe demonstrated the possibility of using tablet‐based automatic assessments for detecting patients with both MCI and AD. In addition, our results suggest that speech data from not only neuropsychological tasks but also when answering everyday questions might contain useful information to help early detection of AD.
Unfolded P53 as a novel lead biomarker for Alzheimer’s disease diagnosis
Authors: Abate Giulia , Fowler Christopher J , Martins Ralph N , Memo Maurizio , Uberti Daniela 
Published: December 2020

AbstractBackgroundBlood‐based biomarkers represent a promising choice for early Alzheimer’s disease (AD) diagnosis and for evaluating the efficacy of novel disease‐modifying therapeutics.The complexity of the disease, where multiple pathogenetic mechanisms are involved, would require a pragmatic approach that includes a biomarkers panel for an individually‐tailored AD diagnosis. Oxidative stress, reactive oxygen and nitrogen species have been well documented in AD, however the potential use in the clinic of the metalloprotein p53 as a lead biomarker for this devastating neurodegenerative disorder has not yet been thoroughly investigated. Thus, the aim of this study was to evaluate the role of a conformational variant of p53 as a lead biomarker (Up532D3A8+) in plasma samples from AD at the pre‐clinical and prodromal stages.MethodPlasma samples from Australian Imaging, Biomarkers and Lifestyle cohort (AIBL) biobank were used to evaluate the concentration of Up532D3A8+ through immunoprecipitation with the 2D3A8 antibody followed by SRM‐MS. A total of 102 plasma samples was studied, which includes at baseline samples from (a) AD patients, (b) Mild Cognitive Impairments (MCI) patients and (c) cognitive normal (CN) individuals, in addition to samples at a later time‐point from (d) individuals that converted to AD in a period of 18‐72 months, (e) MCI patients that converted to AD in a period of 18‐36 months and (f) MCI patients at baseline that have not declined to AD for a period of 36 months. Through using a standard heavy isotype labelled peptide spiked into clinical sample before the assay such as plasma, the absolute abundance of Up532D3A8+ protein isoform or its partial degradation products was measured accurately with a high sensitivity.ResultA specific peptide of Up532D3A8+ as signature of clinical AD progression was detected by 2D3A8 immunoprecipitation and quantified by SRM‐MS. This peptide showed a prognostic value with a sensitivity >90%, specificity >85%, PPV around 80%, NPV >95%.ConclusionThe study presented here strongly supports Up532D3A8+ as a promising lead AD biomarker, in particular for disease prognosis in its asymptomatic stage. Consequently it may become an indispensable tool for patient stratification for clinical trials that aim for the prevention of dementia stage in AD progression.
A co‐creation approach to design the implementation of a multimodal intervention in patients with subjective cognitive decline (PENSA study)
Authors: Forcano Laura , Soldevila‐Domenech Natalia , Rodriguez‐Arjona Maria Dolores , Puig‐Pijoan Albert , Pizarro Nieves , Knezevic Iva , Fauria Karine , Minguillón Carolina , Molinuevo Jose Luis ,   PENSA Study Group
Published: December 2020

AbstractBackgroundIn recent years, there has been a growing concern about the hierarchical relationship between researchers and patients. A change of paradigm has been promoted by recent initiatives supporting an active citizenship involvement in research. The combination of patients’ views together with the expertise of clinicians and researchers may lead to a change on how research actions are identified, designed, conducted and disseminated. Following this approach, we introduced a co‐creation action in the intervention design process of the project Prevention of cognitive decline in APOE‐ɛ4 carriers with SCD after epigallocatechin‐gallate and a multimodal intervention (PENSA study). We aimed to assess participants’ opinion about the multimodal intervention and its viability, and to identify aspects of improvement.MethodsWe performed a qualitative descriptive study in a focus group composed by 10 participants (5 women and 5 men) between 60 and 80 years. Two researchers and a qualitative methodology specialist planned the content of a 2‐hour group session, that was guided by the specialist and audio recorded. Subsequently, an analysis of the thematic content was performed to extract the participants’ global comprehension of the phenomenon.ResultsThe qualitative analysis revealed that participants positively rated the intervention and found it as a useful tool to implement a healthy lifestyle. Facilitators and barriers for the implementation of the multimodal intervention were identified. The former related to the great support received by the health professionals and the opportunity of acquiring reliable knowledge about Alzheimer’s disease and its management. The later were mostly related with time availability and a general worry about the return and dissemination of the study results. Moreover, alternatives and changes were proposed to improve the intervention, such as the possibility of adapting the proposed activities to participants’ preferences. The research team has implemented a number of actions to adequate the multimodal intervention to the participants needs.ConclusionsOur study shows that co‐creation actions considering patients experience represents a rich source of information for designing effective health interventions. The co‐creation process represents an exercise of public commitment in responsible research and innovation.
25‐Hydroxycholesterol amplifies microglial IL‐1beta production in an APOE isoform‐dependent manner
Authors: Wong Man Ying , Lewis Michael , Doherty Jim , Shi Yang , Gong Shiaoching , Qian Mingxing , Cashikar Anil G. , Sullivan Patrick M. , Petsko Gregory A. , Covey Douglas , Gan Li , Holtzman David M. , Paul Steven M. , Luo Wenjie 
Published: December 2020

AbstractBackgroundGenome‐wide association studies of Alzheimer’s disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular and chemical mediators of neuroinflammation in AD remain poorly understood. The oxysterol 25‐hydroxycholesterol (25‐HC) is an important immunomodulator produced by peripheral macrophages with wide‐ranging effects on cell signaling and innate immunity. Genetic variants of the enzyme responsible for 25‐HC production, cholesterol 25‐hydroxylase (CH25H), have been found to be associated with AD.MethodIn the present study, we measured CH25H expression in human AD brain and AD transgenic mouse brains. We also investigated the activity of 25‐HC in LPS‐induced innate immune responses including cytokine production in primary mouse microglia and human iPSC‐derived microglia‐like cells.Resultswe found that CH25H expression is upregulated in human AD brain tissue and in transgenic mouse brain tissue bearing amyloid‐bplaques or tau pathology. Treatment with the toll‐like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) markedly upregulates CH25H expression in the mouse brain and stimulates CH25H expression and 25‐HC secretion in mouse primary microglia. We found that LPS‐induced microglial production of the pro‐inflammatory cytokine IL‐1bis markedly potentiated by 25‐HC and attenuated by deletion of CH25H.The upregulation of LPS‐induced IL‐1bby 25‐HC was validated in human microglia‐like cells derived from iPSCs. Through a 42‐multiplex human cytokine assay, we further found that 25‐HC specifically induces IL‐1beta and IL‐1alpha, with little effects on other cytokines in human microglia‐like cells. Interestingly, microglia expressing apolipoprotein E4 (apoE4), a genetic risk factor for AD, produce greater amounts of 25‐HC than apoE3‐expressing microglia following treatment with LPS. Remarkably, 25‐HC treatment results in a greater level of IL‐1bsecretion in LPS‐activated apoE4‐expressing microglia than in apoE2‐ or apoE3‐expressing microglia. Blocking potassium efflux or inhibiting caspase‐1 prevents 25‐HC‐potentiated IL‐1brelease in apoE4‐expressing microglia, indicating the involvement of caspase‐1/NLRP3 inflammasome activity.Conclusion25‐HC may function as a microglial secreted inflammatory mediator in brain, promoting IL‐1b‐mediated neuroinflammation in an apoE isoform‐dependent manner (E4>>E2/E3) and thus may be an important mediator of neuroinflammation in AD.