bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of ADAM10 and decrease in plaques by a sleep‐inducing supplement
Authors: Pahan Kalipada 
Published: December 2020

AbstractBackgroundOne of the pathologic hallmarks of Alzheimer’s disease (AD) is the presence of extracellular amyloid plaques containing Aβ peptides, which originate from the amyloidogenic proteolytic processing of amyloid precursor protein (APP), through the sequential action of β‐ and γ‐secretases. On the other hand, APP can also be cleaved by a non‐amyloidogenic pathway by α‐secretase “a disintegrin and metalloproteinase” 10 (ADAM10), precluding the formation of Aβ peptides. Therefore, delineating drugs and pathways for stimulating non‐amyloidogenic metabolism of APP and lowering plaques is an important area of research. We have seen that oleamide, a sleep‐inducing supplement in human, is present in hippocampal nuclei as a ligand of peroxisome proliferator‐activated receptor alpha (PPARα).MethodWe monitored ADAM10 and ADAM17 in cultured neurons as well as in vivo in the hippocampus of 5xFAD mice by Western blot and immunohistochemistry. Amyloid plaque was monitored in the hippocampus of oleamide‐fed and unfed 5xFAD mice by Western blot and immunostaining. We also recorded cognitive activities by Barnes maze, T maze and novel object recognition test.ResultThis study underlines the importance of oleamide in increasing the expression of ADAM10 in neurons via PPARα. Moreover, the level of oleamide was less in the hippocampus of 5xFAD mice as compared to non‐Tg mice. Oral administration of oleamide increased the level of this molecule in the hippocampus to stimulate ADAM10, reduce plaques and improve memory and learning in 5xFAD mice. However, oral oleamide remained unable to upregulate ADAM10, lower cerebral plaque load and improve cognitive behaviors in 5xFAD mice lacking PPARα.ConclusionThese results indicate an essential role of PPARα in oleamide‐mediated stimulation of non‐amyloidogenic pathway and suggest that this sleep‐inducing supplement may have therapeutic importance for AD. Supported by Zenith Fellows Award (ZEN‐17‐ 438829) and a grant from NIH (AG050431).
A pilot study on the positive rate of multi‐time point and multiple domain evaluation in cerebrospinal fluid tap test of patients with normal pressure hydrocephalus
Authors: Liu Caiyan , Li Jie , Huang Xinying , Dong Liling , Mao Chenhui , Wei Junji , Hou Bo , Feng Feng , Cui Liying , Gao Jing 
Published: December 2020

AbstractBackgroundThe CSF tap test evaluation vary a lot in different medical center, which result in the wide range of sensitivity. Our study aimed to explore the effect of multi time point and multiple domain evaluation on the determination of CSF tap test results in patients with normal pressure hydrocephalus.MethodA total of 150 outpatients with NPH 2013‐2018 from the Department of Neurology of Peking Union Medical College Hospital were enrolled in this study. All patients underwent detailed neuropsychological (MMSE, MOCA, Trail Making Test , Digital Symbol, Stroop‐c test, Grooved pegboard test) and walking ability (10 meter walking test, 5 meter up and go test), and head MRI examination. Patients who did not complete the four time point’s evaluation of CSF tap test to eliminate severe dementia and various reasons. The positive criteria were that the performance of either time or steps in walking test was 20% higher than the baseline level, or both were 10% higher. In the cognitive test, the score of any test is 20% higher than the baseline as a positive criterion. According to this standard, the positive rates of each evaluation test and three evaluation time points were calculated and compared.ResultThe positive rate of 5 meter up and go test on 8 hours, 24 hours and 72 hours after CSF tap test was 40.6%, 42.0%, 48.9%, the positive rate of 10‐meter walking test was 35.8%, 30.9%, 40.7% respectively; the positive rate of Digital Symbol was 23.8%, 38.1%, 42.9% respectively; the positive rate of Trail Making T test was 38.7%, 45%, 57.9%; the positive rates of Stroop‐c performance were 27.0%, 39.3% and 49.1% respectively; the positive rates of Grooved pegboard test on 8 hours, 24 hours and 72 hours after CSF tap test were 25%, 27.9% and 39.7%.ConclusionThe positive rate of 5 meter up and go test is higher than that of 10 meter walking test, and the positive rate of 24‐hour and 72 hour comprehensive evaluation combined with walk and cognitive evaluation is higher.
Improving the Experience of Dementia and Enhancing Active Life (IDEAL): Investigating the perspectives of people from ethnic minority communities
Authors: van den Heuvel Eleanor , Victor Christina R , Clare Linda 
Published: December 2020

AbstractBackgroundPeople from African Caribbean and South Asian backgrounds come to the attention of memory services at a much later stage in the dementia process than the majority population in the UK, often as a result of a crisis (1,2,3). We aim to discover barriers to service use as well as factors that are important maintaining a good quality of life for people and families affected by dementia.MethodTwenty‐two semi‐structured interviews were conducted with community leaders, older people with memory problems (with and without a dementia diagnosis) and family caregivers from the target communities. Interviews were audio recorded, transcribed and thematically analysed.ResultBarriers to service use included acceptance of cognitive decline as normal ageing, stigma associated with metal health, a perceived lack of culturally‐appropriate services and for some communities a profound distrust of UK services and institutions. Important factors for ageing well with memory problems and dementia included the availability of family support, religion and support from the faith community, and recognition of specific dietary and personal care requirements and preferences.ConclusionImproving the experience of living with dementia for Britain’s ethnic minority communities will depend on educating service providers about community members’needs and aspirations and increasing community awareness of dementia and the help that is available. 1. Botsford, J., Clarke, C.L. and Gibb, C.E. (2012) 'Dementia and relationships: experiences of partners in minority ethnic communities', Journal of Advanced Nursing, 68(10), pp. 2207‐2217. 2. Johl, N., Patterson, T. and Pearson, L. (2016) 'What do we know about the attitudes, experiences and needs of Black and minority ethnic carers of people with dementia in the United Kingdom? A systematic review of empirical research findings', Dementia, 15(4), pp. 721‐742. 3. Mukadam, N., Waugh, A., Cooper, C. and Livingston, G. (2015) 'What would encourage help‐seeking for memory problems among UK‐based South Asians? A qualitative study', BMJ open, 5(9), pp. e007990.
Efficacy of cognitive‐behavioral interventions for caregivers of individuals with a neurocognitive disorder: A systematic review and meta‐analysis
Authors: Verreault Phylicia , Turcotte Valérie , Ouellet Marie‐Christine , Hudon Carol 
Published: December 2020

AbstractBackgroundBy 2025, 34 millions of people worldwide will be living with Alzheimer's disease or other form of dementia (i.e., neurocognitive disorders). Symptoms of cognitive disorders non‐exclusively include memory deficits and executive deficits, but also functional repercussions in activities of daily living such as doing chores, taking medication and preparing meals. People with neurocognitive disorders often rely on a caregiver to alleviate the impact of their symptoms, but this helps is not without consequences on the caregiver. Indeed, caregivers report subjective burden, depressive symptoms, stress and anxiety, and report a lower quality of life than non‐caregivers. Multiple cognitive‐behavioral therapy (CBT) trials have been conducted to reduce these symptoms, and two meta‐analyses suggest that this method could be beneficial to reduce depressive symptoms. However, no meta‐analysis has been conducted to evaluate the efficacy of this type of intervention on subjective burden.MethodEligibility criteria for the individual studies were determined using the PICOS strategy recommended by the PRISMA statement. Articles were selected from PsychNet, MedLine, AgeLine, and ProQuest Dissertation and Theses for the period of 2000 to 2017. Article's selection, data extraction and analysis of bias for individual studies were completed by two independent authors using a consensus procedure when discrepancy occurred. The statistics Q, df, p value and I‐square, and Tau‐square were computed. Standardized effect sizes (Hedge's g) were also computed for all studies.ResultA total of 20 articles were included in the systematic review. Statistics suggested no significant heterogeneity and a fixed‐effect model was used. Ten studies (N = 200 caregivers) evaluated the efficacy of CBT on subjective burden and the meta‐analysis suggested a significant reduction of subjective burden following CBT. Additionally, 17 studies (N = 437 caregivers) evaluated the efficacy on depressive symptoms and the meta‐analysis revealed a significant reduction following CBT for these caregivers.ConclusionCBT for caregivers of individuals with a neurocognitive disorder are beneficial in reducing subjective burden and depressive symptoms, but had no impact on stress, anxiety and quality of life.
Adaptive and maladaptive behaviors of persons diagnosed with mild cognitive impairment
Authors: Gibson Allison , Bardach Shoshana H , Jicha Gregory A 
Published: December 2020

AbstractBackgroundMild cognitive impairment (MCI) can disrupt an individual’s lifestyle. The biopsychosocial model serves as a promising clinical framework to understand the impact of MCI on the individual. Receiving a MCI diagnosis can result in behavioral responses that are either adaptive or maladaptive. Maladaptive behavior refers to types of behaviors that inhibit a person’s ability to adjust to particular situations. For many, an MCI diagnosis leads to maladaptive behaviors, stemming from emotional turmoil and lack of clarity about the future. Developing strategies to circumvent the development of such behaviors could significantly reduce morbidity and mortality in patients with MCI.MethodsThe Aging and Memory Quality of Life (AMQoL) Survey assesses aspects of a biopsychosocial assessment in order to determine the attitudes and behaviors of persons diagnosed with MCI (38 items). The tool was utilized to identify adaptive and maladaptive behaviors. Data were collected on the impact of MCI from 45 individuals diagnosed with MCI and 45 cognitively normal participants serving as control subjects matched for age, gender, and education to distinguish responses to MCI from regular age‐related adaptations (n=90).ResultsGiven the categorical nature of the survey, non‐parametric tests were conducted using the Mann‐Whitney u‐test. Subject groups’ mean ranks and p‐values are reported. MCI subjects were less confident, less interested in learning new things and less excited about the future (p‐values 0.027, <0.0001, and 0.016) compared to the cognitively normal respondents. MCI subjects were more likely to want help managing financial affairs (p=0.009) than their cognitively normal counterparts. Subjects scoring high on maladaptive behaviors or MCI were younger, healthier, and scored lower on category fluency, Trailmaking A&B, and Wais digit‐symbol tests (p‐values 0.03, 0.003, 0.008, 0.001, 0.03, 0.04). Further, less than half of individuals with MCI were on medications for cognition.ConclusionAnalyses of the data demonstrate a significant potential for maladaptive responses to an MCI diagnosis. Developing strategies to circumvent the development of such behaviors could significantly reduce morbidity and mortality. Interventions to counter the negative biopsychosocial effects of MCI diagnosis could improve the quality of life of individuals diagnosed with MCI.
Phospho‐tau217 and phospho‐tau181 in plasma and CSF as biomarkers for Alzheimer’s disease
Authors: Janelidze Shorena , Palmqvist Sebastian , Quiroz Yakeel T. , Lopera Francisco , Stomrud Erik , Su Yi , Chen Yinghua , Serrano Geidy E , Leuzy Antoine , Mattsson Niklas , Strandberg Olof , Smith Ruben , Villegas Andres , Sepulveda Diego , Chai Xiyun , Proctor Nicholas , Zetterberg Henrik , Beach Thomas G. , Blennow Kaj , Reiman Eric M. , Dage Jeffrey L. , Hansson Oskar 
Published: December 2020

AbstractBackgroundCerebrospinal fluid (CSF) p‐tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD) reflecting abnormal tau metabolism in the brain. We have recently shown that also plasma p‐tau181 is a promising biomarker for AD (Janelidze et al, Nature Medicine, 2020). We now evaluate whether CSF p‐tau217 or plasma p‐tau217 are even better biomarkers.MethodsWe compared CSF p‐tau217 to CSF p‐tau181 in the Swedish BioFINDER‐1 cohort (n=194). We next evaluated plasma p‐tau217 and plasma p‐tau181 in three cohorts with 1,438 participants: an Arizona‐based neuropathology cohort, including 34 AD and 47 non‐AD participants; the Swedish BioFINDER‐2 cohort, including cognitively unimpaired (n=312) participants, and clinically diagnosed patients with mild cognitive impairment (MCI, n=188), AD dementia (n=126), and other non‐AD neurodegenerative diseases (n=109); a Colombian autosomal‐dominant AD kindred, including 365 PSEN1E280A‐carriers and 257 non‐mutation carriers.ResultsCSF p‐tau217 had stronger correlations with the tau‐PET tracer, and more accurately identified individuals with abnormal tau‐PET scans (AUC=0.93) than CSF P‐tau181. CSF P‐tau217 correlated better than p‐tau181 with CSF and PET measures of neocortical amyloid‐β burden and more accurately distinguished AD dementia from non‐AD neurodegenerative disorders. Antemortem plasma P‐tau217 differentiated individuals with intermediate‐to‐high likelihood of AD according to neuropathology from those without AD (AUC=0.89) and performed significantly better than plasma P‐tau181. Plasma P‐tau217 also differentiated clinical AD dementia from non‐AD neurodegenerative diseases (AUC=0.96) significantly better than plasma P‐tau181, plasma neurofilament light, and established MRI measures, and similar to CSF P‐tau217, CSF P‐tau181, CSF Aβ42/40, and tau‐PET. Increased plasma P‐tau217 was observed already in the pre‐symptomatic stages of AD. In PSEN1 mutation carriers the increase started at age 25, about 20 years prior to estimated onset of MCI. Plasma P‐tau217 correlated with cerebral tau tangle densities in subjects with neuritic plaques (r=0.64). It predicted abnormal tau‐PET scans (AUC=0.95) significantly better than plasma P‐tau181, plasma neurofilament light, CSF P‐tau181 and CSF Aβ42/Aβ40, and similar to CSF P‐tau217.ConclusionsPlasma and CSF P‐tau217 reflect brain tau burden, increases early in AD, and differentiates AD from other neurodegenerative diseases.
Do deficits in mitochondrial spare respiratory capacity contribute to neuropsychological changes seen in Alzheimer’s disease?
Authors: Bell Simon M. , De Marco Matteo , Barnes Katy , Shaw Pamela , Ferraiuolo Laura , Blackburn Daniel J. , Mortiboys Heather , Venneri Annalena 
Published: December 2020

AbstractBackgroundIn clinical settings, AD is defined by characteristic deficits in neuropsychological testing supported by amyloid and tau biomarkers and neuroimaging abnormalities. The biological cause of neuropsychological changes is not established. Tau deposition correlates with, but does not fully account for all observed neuropsychological impairments. We have shown mitochondrial spare respiratory capacity (MRSC) is lowered in AD patient fibroblasts. This study investigates if fibroblast mitochondrial functional abnormalities correlate with neuropsychological/neuroimaging changes in AD.Method10 AD patient and 10 control fibroblast samples were taken via skin biopsy. Adenosine Triphosphate (ATP) and extracellular lactate were measured using luminescent and fluorescent protocols respectively. Mitochondrial membrane potential (MMP) was measured using tetramethylrhodamine dye. Mitochondrial respiration and glycolytic function were measured using a Seahorse XF Analyzer. In‐depth Neuropsychological profiling, and brain structural MRIs were undertaken on all participants. Correlations were performed between MMP, MRSC and neuropsychological/MRI AD markers.ResultReductions in delayed (p<0.0001) and immediate recall (p<0.0001), semantic fluency (p<0.0001), phonemic fluency (p=0.0033) and MMSE (p=0.0009) scores were seen in AD patients. After controlling for age, education and brain reserve; left hippocampal (p=0.001), left parietal (p=0.002), right parietal (p=0.001) and anterior medial prefrontal cortical (p=0.017) gray matter volumes were reduced in AD patients. Fibroblast metabolic markers showed a reduction in MMP (p=0.001), MRSC (p<0.0001), glycolytic reserve(p=0.05), and extracellular lactate (p<0.05) in AD patients. MRSC and MMP correlated significantly with immediate recall ([MRSC, p=0.0041],[MMP, p=0.0115]), delayed recall ([MRSC, p=0.0013],[MMP, p=0.0138]) and semantic memory ([MRSC, p=0.0039],[MMP, p=0.009]) tests. The correlations between MRSC and neuropsychological measures remained after controlling for age, education and brain reserve. No correlations were seen between grey matter volumes and fibroblast metabolism.ConclusionThis study highlights how in‐depth metabolic analysis of sporadic AD fibroblasts identifies functional abnormalities that correlate with neuropsychological features distinctive to AD. This work may also explain how some of the fundamental biological processes that are affected in Alzheimer’s disease may contribute to the neuropsychological profiles that define the condition.
Associations of white matter hyperintensities with cognitive decline: A longitudinal study
Authors: Wang Yan‐li , Yu Jin‐Tai , Xu Jun , Tan Lan 
Published: December 2020

AbstractBackgroundWhite matter hyperintensities (WMHs), mainly caused by cerebrovascular injury, may lead to cognitive impairment. In order to identify whether the volume of WMHs is associated with cognitive decline over years, this longitudinal study involved 818 individuals from the ADNI‐2 dataset from August 2010 to May 2017.MethodCross‐sectional and longitudinal associations of WMHs with 8 cognitive domains were explored, using Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer Disease Assessment Scale‐Cognitive (ADAS‐Cog13), Rey Auditory Verbal Learning Test (RAVLT), Functional Assessment Questionnaire (FAQ), executive function (ADNI‐EF), and memory function (ADNI‐Mem). The association analyses were performed using multiple linear regression models, linear mixed models, Spearman rank correlation and Kaplan‐Meier survival curves.ResultThe volumes of WMHs were greater in patients with AD dementia compared with controls (p<0.001) and MCI (p=0.006) patients at baseline. The bigger volumes of WMHs correlated with worse performances on ADAS‐Cog13 and ADNI‐EF (p=0.029; p=0.0032) at baseline and MMSE, MoCA, CDRSB, ADAS‐Cog13, FAQ and ADNI‐Mem (overall p<0.05) longitudinally, after adjusting for age, sex, educational level, apolipoprotein E ε4 genotype, hypertension, hyperlipidemia, diabetes, smoking, infarction and diagnosis. And the correlations between the change rate of WMHs and change rates of MMSE, MoCA, CDRSB, FAQ, ADNI‐EF and ADNI‐Mem were statistically significant. Furthermore, patients with high WMH volumes showed an increased likelihood of dementia.ConclusionThe results of the study suggest that WMH volume is associated with cognitive decline, and it contributes to the conversion to AD.
Determining the utility of epigenetic modulators to treat Alzheimer’s disease
Authors: Imm Jennifer L. 
Published: December 2020

AbstractBackgroundIt has been previously demonstrated that there are robust and reproducible changes in DNA methylation in Alzheimer’s disease (AD). As these epigenetic changes mediate long lasting alterations in the brain they are attractive drugs targets to reverse disease effects which are precipitated or propagated by epigenetic aberrations. The Oxford drug discovery institute have available a panel of modulators that are known to target proteins involved in epigenetic mechanisms, however, we have little understanding of the cellular effects of these modulators in brain cells. Through this project we aim to identify the target epigenetic pathways of the chemical probes and to try and relate these to the pathways known to be dysregulated in AD.MethodHuman induced pluripotent stem cell (iPSC)‐derived neurons and microglia were differentiated and treated with 30 different epigenetic modulators (at 3µM) for 24 hours. DNA was extracted, bisulfite treated before being run on the Illumina Infinium EPIC BeadChip array to assess DNA methylation. After quality control checks and normalization, we identified differentially methylated positions being altered upon treatment and subsequent cellular pathways using network‐based and pathway analysis.ResultsThis study has identified methylomic variation associated with treatment. We have also shown that there are differences in the epigenetic age and mitotic age caused by cell type.ConclusionWe have shown that there are epigenetic changes upon neuronal and microglial treatment with drugs known to alter epigenetic processes. In the future it would be interesting to test these compounds in iPSC‐derived neurons and glia from patients bearing AD‐associated genetic mutations.
Long‐term effects of work‐related sleep disruption on cognitive function and brain amyloid‐β load
Authors: Thomas Jana , Mentink Lara J. , Booij Jan , Olde‐Rikkert Marcel , Overeem Sebastiaan , Kessels Roy P.C. , Claassen Jurgen A.H.R. 
Published: December 2020

AbstractBackgroundRecent evidence indicates that disrupted sleep could contribute to the development of Alzheimer’s disease (AD) by influencing the production and/or clearance of the amyloid‐β protein. Studies however are limited to acute, short‐term effects. Therefore, we investigated the association between long‐term work‐induced sleep disruption, cognition, and brain amyloid‐β accumulation in a case‐control setting.MethodA sample of 25 middle‐aged male maritime pilots was recruited through the national organization of Dutch maritime pilots, with an exposure of >15 years to work‐induced sleep disruption. Men with a normal sleep pattern served as controls. Participants completed 10 days of actigraphy (Actiwatch 2, Philips Respironics) combined with a sleep‐wake diary, and 20 days of at‐home EEG sleep measurements. They underwent one night of polysomnography (PSG), followed by comprehensive assessment of cognitive function. Additionally, participants underwent amyloid PET‐CT (Positron Emission Tomography‐ Computed Tomography) to measure brain amyloid accumulation.Results19 male maritime pilots (mean age=53±3.4) and 19 male controls (mean age=57±2.9) completed the study. Maritime pilots reported significantly worse sleep quality (Pittsburgh Sleep Quality Index (PSQI)=8.8±2.9) in a workweek, compared to controls (PSQI=3.2±1.4; 95% CI 0.01 to 2.57; P=.049). This was confirmed with actigraphy‐based measures of sleep efficiency (controls: 89.3% ±4.3; pilots: 86% ±3.8; 95% CI 0.43 to 6.03; P=.03). Home EEG recordings in maritime pilots showed significantly reduced total sleep during work weeks compared to rest weeks (318.6 min (250.21–352.93) vs. 406.17 (340–425.98); P=.001), with reduced slow wave sleep (36.75 (32.30–58.58) vs. 51.34 (48.37–69.30); P=.005). There were no differences between maritime pilots and controls in any of the cognitive domains. Mean global cortical standard uptake value ratios for 18 F‐flutemetamol PET‐CT in maritime pilots was 1.009 (±0.059; 95% CI 0.980 to 1.037) indicating no evidence of abnormal amyloid‐β accumulation, which was confirmed by visual reads.ConclusionIn this study population, long‐term intermittent week‐long sleep disruption did not result in significant brain amyloid accumulation nor in cognitive decline. This may indicate that amyloid accumulation during periods with sleep disruption can be reduced in periods with normal sleep, this hypothesis must be tested in future investigations.