bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between cerebral microbleeds, ventricular enlargement and white matter hyperintensities in Alzheimer’s disease
Authors: Kuroda Takeshi , Honma Motoyasu , Mori Yukiko , Futamura Akinori , Sugimoto Azusa , Yano Satoshi , Kinnno Ryuta , Murakami Hidetomo , Ono Kenjiro 
Published: December 2020

AbstractBackgroundTo investigate whether the number of cerebral microbleeds (CMB) could be a useful indicator to predict glymphatic system dysfunction in Alzheimer’s disease (AD) patients, by comparing the degree of cerebral spinal fluid (CSF) and interstitial fluid (ISF) stasis.MethodForty probable AD patients were included, with those exhibiting two or more CMB were included in the multiple CMB group (mCMB, n = 21, mean = 11.1), and none or one CMB included in the non‐multiple CMB group (nmCMB, n = 19, mean = 0.84). CMB were defined in axial gradient recalled echo (GRE) T2*‐weighted images. Evans index (EI) was calculated to measure lateral ventricle enlargement, Voxel‐based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) software was used to determine the extent of gray and white matter atrophy, and Fazekas scale (FS) was used to determine white matter hyperintensities (WMH).ResultEI was significantly larger in mCMB than in nmCMB, while the gray and white matter volume was not different between groups. Thus, the difference in lateral ventricle enlargement between AD with and without multiple CMB reflects a combination of the degree of brain atrophy and the extent of CSF stasis. FS was higher in mCMB than in the nmCMB, suggesting the failure of ISF elimination was more severe in mCMB cases.ConclusionThe difference in lateral ventricle enlargement and WMH between AD with or without multiple CMB may reflect a difference in the degree of CSF/ISF stagnation.
Self‐reported and informant‐reported assessments of neuropsychological conditions in a Lebanese sample of community‐dwelling older adults in Lebanon
Authors: Elbejjani Martine , El Hachem Rita , Chaaya Monique 
Published: December 2020

AbstractBackgroundAccumulated data highlight a significant role for mental health in influencing and exacerbating the risk, detection, and progression of cognitive decline and aging‐related disorders. In parallel, several findings suggest cultural and contextual differences in the manifestation and recognition of mental health problems. In Lebanon, data on mental and cognitive health and on their assessments are scarce. We examined the agreement between self‐reported and informant‐reported assessments of depressive and anxiety symptoms in a Lebanese community‐based sample of older adults.MethodData come from a Lebanese cohort of older adults (n=502, age=75.5 (SD=7.2); 56.2% women). Depressive and anxiety symptoms were self‐rated using the Geriatric Mental State (GMS) AGECAT and informant‐rated using the Neuropsychiatric Inventory Questionnaire (NPI‐Q). We estimated Cohen’s Kappa and investigated factors related to mismatch in reports using logistic regression models; explanatory factors included participants’ cognitive functioning and participants’ and informants’ demographic and socioeconomic indicators. Data processing is still ongoing to include more participants.ResultPreliminary results showed that 10.6% and 1.6% of participants self‐reported depression and anxiety symptoms and 4.6% and 2% had depression and anxiety symptoms based on informant’s reports, respectively. Cohen’s Kappa was 0.38 for depression and 0.32 for anxiety symptoms; 69.8% and 62.5% of those reporting depressive and anxious symptoms were not reported to have these symptoms by their informants and 30% and 70.4% of informant‐reported depression and anxiety were not reported by participants. Men and participants with higher educational attainment had lower odds of mismatch between self‐ and informant‐reports (OR=0.46 (95% CI=0.24, 0.88) and OR=0.54 (95% CI=0.28, 1.04)); current employment of both participants and informants was associated with lower mismatch (OR=0.19 (95% CI=0.07, 0.54) and OR=0.58 (95% CI=0.32, 1.1). Higher cognitive scores were associated with lower mismatch (OR=0.90 (95% CI=0.81, 0.99).ConclusionResults indicate a weak agreement between self‐reported and informant‐reported neuropsychological symptoms and that the majority of older adults with symptoms were not identified by their informants. More work is needed to improve assessments of neuropsychological symptoms and identify mechanisms underlying discrepancies in assessments in the Lebanese population to better track neurocognitive and health changes at older age.
Relationship between genetic risk for Alzheimer's, cognition and neuropsychiatric symptoms: A case study of DNA sampling and analysis through digital platform cohort studies
Authors: Creese Byron , Brooker Helen , Aarsland Dag , Corbett Anne , Ballard Clive , Ismail Zahinoor 
Published: December 2020

AbstractBackgroundWith the evolution of technologies to extract DNA and undertake analysis from saliva samples, it is now feasible to collect postal samples for genetic analysis as part of cohort studies run on digital platforms. Ethics and engagement will be discussed and Mild Behavioral Impairment (MBI) is presented as an example of where this approach has delivered a substantial and cost‐effective study.MBI, a late‐life neuropsychiatric syndrome, is associated with faster progression to dementia and Aβ deposition even in healthy adults. MBI screening may enrich samples with individuals at risk for dementia, with benefits to clinical studies and possibly trials.Method25,000 participants from the PROTECT digital platform were invited to provide a saliva sample by post. Ethics approval was underpinned by an on‐line consent process, genotypes were not disclosed to participants. Polygenic scores (PRS) for Alzheimer’s disease (AD) were calculated and split by tertile (representing low, medium and high AD genetic risk). Data were analysed as a whole sample then stratified by the presence of MBI.Result87% of PROTECT participants agreed to provide genetic samples by post. 10,000 of these have been genotyped. 75% of the sample were women and the mean age was 62 (range: 50‐100). At the time of data freeze, genetic, MBI and cognitive data were available for 3,126. AD genetic risk was associated with a lower cognitive score (F(2,3119)=3.93, p=0.02; mean difference between low and high genetic risk: ‐15, p=0.02, Cohen’s d=0.13). In stratified analysis, genetic risk for AD was associated with worse cognition but only in the MBI group (MBI: F(2,1746)=4.95, p=0.007; no MBI: F(2,1366)=0.72, p=0.49). There was a significant difference between the high and low genetic risk groups (mean difference: ‐0.22, p=0.005); the effect size was stronger than in the whole sample analysis (Cohen’s d increase from 0.13 to 0.19).ConclusionHigh degrees of engagement can be achieved to obtain DNA samples from participants in online cohort studies. With respect to MBI, these findings demonstrate that neuropsychiatric symptoms may modify the relationship between genetic risk for AD and cognitive impairment. MBI screening may represent a useful sample enrichment strategy for clinical studies and trials.
Quantitative mass spectrometry suggests beta‐synuclein as promising blood marker for synaptic degeneration in Alzheimer's disease
Authors: Oeckl Patrick , Halbgebauer Steffen , Straub Sarah , von Arnim Christine , Diehl‐Schmid Janine , Frölich Lutz , Grimmer Timo , Hausner Lucrezia , Denk Johannes , Jahn Holger , Weishaupt Jochen H. , Ludolph Albert , Otto Markus 
Published: December 2020

AbstractBackgroundSynaptic degeneration is a major hallmark of Alzheimer's disease (AD) and the best pathological correlate of cognitive dysfunction. Synaptic markers are therefore a highly desired read‐out for patient diagnosis and possible follow‐up in clinical trials in the mainly unsuccessful AD drug development. Several synaptic markers for AD are described in cerebrospinal fluid (CSF) but studies in blood were not successful so far.MethodWe used quantitative mass spectrometry (IP‐MS, MRM) to measure the presynaptic protein beta‐synuclein in CSF and blood from 363 patients: AD (n=64), Creutzfeldt‐Jakob disease (CJD, n=25), behavioural variant frontotemporal dementia (bvFTD, n=16), dementia with Lewy bodies/Parkinson´s disease dementia, (DLB/PDD, n=13), Parkinson´s disease (PD, n=25), amyotrophic lateral sclerosis (ALS, n=30) and non‐neurodegenerative controls (Con, n=45). Changes in AD were validated in two independent validation cohorts from other clinical centers (AD: n=40 and n=49, Con: n=44 and n=25). Group differences were compared by non‐parametric tests and data correlated with clinical scores (MMSE, CDR).ResultWe observed increased concentrations of beta‐synuclein in CSF and blood of AD patients (CSF: median 979pg/mL, IQR: 738‐1223pg/mL vs. 659pg/mL, IQR: 521‐860pg/mL in controls; Serum: 12.9pg/mL, IQR: 10.6‐16.4pg/mL vs. 8.9pg/mL, IQR: 7.1‐10.4pg/mL in controls, p<0.01) and confirmed this finding in the two validation cohorts. Beta‐synuclein was already increased in patients with mild cognitive impairment due to AD (p<0.01). CSF and serum beta‐synuclein was also markedly increased in CJD (CSF: 19324pg/mL, IQR: 10560‐42570pg/mL; Serum: 479pg/mL, IQR: 259‐843pg/mL, p<0.001) but not bvFTD, DLB/PDD, PD or ALS. The diagnostic sensitivity and specificity for CJD versus other neurodegenerative diseases was ³96%.ConclusionThese findings suggest beta‐synuclein as a candidate blood marker for synaptic degeneration which might be used in clinical AD trials and patient follow‐up as part of the recently suggested ATN biomarker panel. It can also serve in the differential diagnosis of CJD.
Potential synergistic effect between Fortasyn Connect and cholinesterase inhibitors in patients with early stages (very mild and mild) of dementia due to Alzheimer disease in common medical practice: An observational, non‐interventional study
Authors: Fernandez Felix Vinuela , Crespo Angeles Barro 
Published: December 2020

AbstractBackgroundDetails implementation of an innovative care program or practice: Fortasyn connect medical food, approved for early stages of Alzheimer dementia, can have a synergistic effect with cholinesterase inhibitors drugs.ObjectivesTo analyse the possible synergistic effect between Fortasyn Connect medical food and Cholinesterase Inhibitors drugs in Alzheimer disease patients in a common medical practice.Patients and Methods60 patients at early stages of dementia due to Alzheimer disease were followed. CDR (Clinical Dementia Rating) scale was administered at the beginning and at the end of the follow‐up period. The rate of change of CDR‐SB (sum of Blocks) was chosen as a efficacy criteria. Informed Consent was aquired. An approval of the Ethical Committee of the protocol was obtained. SSPS (v20) was used as a Statistical Software.ResultsThe combination therapy with Fortasyn Connect and Cholinesterase inhibitors was well tolerated. There were no significative advers effect. The patients were distribute at the final visit in 4 groups: Those who had taken both Fortasyn Connect and Cholinesterase inhibitors (Group 1), those who had taken Fortasyn Connect and no Cholinesterase inhibitors (Group 2), those who had taken Cholinesterase inhibitors and non Fortasyn Connect (Group 3), those who had not taken neither Fortasyn Connect nor Cholinesterase inhibitors (Group 4). There was a statistical difference between the Group 1 with the Group 3 and Group 4, indicating a potential synergistic effect between both therapies.ConclusionsThe combination therapy with Fortasyn Connect medical food and Cholinesterase inhibitors was well tolerated. It seem to be a potential synergistic efect between Fortasyn Connect medical food and Cholinesterase inhibitors Drugs. An statistical difference between the Group 1 (Fortasyn Connect medical food and Cholinesterase inhibitors therapy) with the Group 3 (Cholinesterase Inhibitor alone) and Group 4 (Fortasyn Connect medical food and Cholinesterase inhibitors therapy), indicating a potential synergistic effect between both therapies. Due to the limitations of this preliminary study (non‐blinded, non randomized, small sample of patients, non placebo control), more studies are needed.
Risk and protective factors affecting the quality of life of family carers of people with dementia
Authors: Contreras Milena L , Mioshi Eneida , Kishita Naoko 
Published: December 2020

AbstractBackgroundContreras conducted a comprehensive meta‐analysis on predictive factors of QoL among family carers. The findings suggested that previous studies exclusively relied on generic QoL measures (e.g., feeling satisfied with own physical health) to assess wellbeing among this population. The level of generic QoL is often considered to largely depend on physical health conditions and level of independence, which could be problematic when used with older populations. To further build the evidence base, the current empirical study aimed to investigate the impact of common risk factors (i.e., care recipient’s neuropsychiatric symptoms, carer depression, anxiety and objective burden) on old age‐specific QoL (e.g., feeling valued in the community) among family carers, considering the increasing age of this population. It also aimed to explore the role of protective factors that have been proved to predict wellbeing in other populations but have not been studied yet in carers such as psychological flexibility and self‐compassion. Other potential protective factors such as carer’s knowledge about dementia and the number of hours of support they receive from other family members were also considered in the model.MethodEighty‐five family carers (Mean age=69.5, SD=12.9; 67.1% female) were recruited in the UK. Most of the participants were looking after a spouse (67.0%) with Alzheimer’s (43.5%) or mixed dementia (18.8%). Two separate multiple regression analyses were conducted with old age‐specific QoL as a dependent variable. First, all risk factors (i.e., neuropsychiatric symptoms, depression, anxiety and objective burden) were entered to the model as independent variables. In the second analysis, psychological flexibility, self‐compassion, knowledge about dementia and the number of hours of support carers receive from other family members were entered as independent variables to assess the impact of protective factors.ResultAnxiety was the only significant risk factor predicting old age‐specific QoL (β=‐.37) and psychological flexibility was the only significant protective factor predicting QoL (β=‐.44).ConclusionThese findings suggested that improving carer’s anxiety and psychological flexibility may be particularly important in promoting their old age‐specific QoL Future interventions should target these key variables to achieve the desired result of improving carer QoL.
CRISPR/Cas9 genome editing of CLU to examine clusterin’s contribution to neurodegeneration and Alzheimer’s disease
Authors: Foster Evangeline M. , Ribe Elena M. , Robbins Jacqueline , Hublitz Philip , Pangalos Menelas , Buckley Noel , Lovestone Simon , Neuroscience Translational , Research Dementia 
Published: December 2020

AbstractBackgroundTraditionally, clusterin is referred to as a secreted protein however, more recent evidence indicates clusterin may exist intracellularly where it may have a pro‐apoptotic role. Previously, our lab observed altered clusterin trafficking in rodent neurons in response to amyloid‐β suggesting it may be a key factor in neurodegeneration. We aim to use CRISPR/Cas9 in human iPSCs to explore the contribution that clusterin plays in cellular vulnerability to amyloid‐β.MethodWe aim to remove exon 2 from CLU since this exon contains the ER‐signal peptide thought to be required for secretion of clusterin protein. So far, we have generated heterozygous exon 2 knockout iPSCs (exon 2+/‐) which have been differentiated into cortical neurons and astrocytes. Clusterin gene and protein expression has been characterised in these iPSCs compared to control iPSCs. Response of control and exon 2+/‐ neurons and astrocytes to amyloid‐β treatment has also been explored.ResultSurprisingly, exon 2+/‐ iPSCs express significantly less intracellular clusterin than control iPSCs. Secreted clusterin expression is unaltered by the edit achieved but glycosylation state is altered. We build on previous findings in rodent neurons, showing that clusterin trafficking is also altered by amyloid‐β in both control iPSC‐neurons and iPSC‐astrocytes. This response is observed in exon 2+/‐ neurons but is absent in exon 2+/‐ astrocytes. Divergence in gene expression changes of DKK1‐signature genes is observed. Here, we describe differences in both gene and protein expression changes in response to amyloid‐β treatment in control and exon 2+/‐ cells.ConclusionCurrently, we are exploring whether differences observed in neuronal and astrocytic responses of exon 2+/‐ cells convey protection or vulnerability to amyloid‐β induced toxicity. To do so, we are using imaging techniques to quantify changes in cell death and neurite projections for both genotypes in response to treatment.
The context effect in facial emotion perception increases with age
Authors: Bartsch Kaja , Jarsch Marianne , Monsch Andreas U. , Kressig Reto W. , Sollberger Marc 
Published: December 2020

AbstractBackgroundThere is evidence that age and context (e.g. stimuli presentation) influence the way we perceive emotions (Barrett, Mesquita & Gendron, 2011; Stanley & Isaacowitz, 2015). We investigated whether there is an age‐dependent context effect on the perception of static facial emotions.MethodIn this cross‐sectional study, 240 cognitively and psychically healthy subjects (50% female), evenly distributed between 34 and 90 years old, participated. Two facial emotion intensity perception tasks (Chiu et al., 2016; Chui et al., 2018) comprising different stimuli presentations, were administered: In the congruent context, facial emotions (i.e., anger, fear, disgust, happiness and sadness) were rated on a seven point Likert scale in terms of intensity from 'not perceived' to 'very strongly perceived'. In the incongruent context each facial stimulus was shown consecutively five times and had to be rated not only on the congruent emotion, but also on the other four incongruent emotions (e.g., rating on happiness, anger, disgust, fear and sadness when a happy face was shown). Congruent scores of the two tasks were used to investigate the potential context effect on emotion perception.We performed a linear mixed effects analysis of each emotion, entering the interaction term age x context, sex and gender of the stimulus as fixed effects; subjects were treated as random effects.ResultWith increasing age, subjects perceived happiness (t(345) = 3.04, p < 0.01), disgust (t(717) = ‐6.42, p < 0.001, sadness (t(717) = ‐2.81, p < 0.001) and fear (t(717) = ‐2.13, p< 0.05) less intensely in the incongruent compared to the congruent context. In contrast, we found no age‐dependent context effect in the perception of anger.ConclusionWe found a significant age‐dependent context effect in the perception of happiness, disgust, sadness and fear. Older subjects were more prone to context in terms of varying stimuli presentation than younger subjects, possibly also due to a decrease of cognitive functions in older age e.g., mental flexibility (Mather, 2016). Our results contribute to a better understanding of influential factors on emotion perception, which is critical when interpreting patients’ scores on an emotion perception task.
Amygdalar nuclei and hippocampal subfields on MRI: Test‐retest reliability of automated segmentation in old and young healthy volunteers
Authors: Quattrini Giulia , Pievani Michela , Jovicich Jorge , Aiello Marco , Bargalló Nuria , Barkhof Frederik , Bartrés‐Faz David , Beltramello Alberto , Pizzini Francesca B , Blin Olivier , Bordet Régis , Caulo Massimo , Constantinides Manos , Didic Mira , Drevelegas Antonios , Ferretti Antonio , Fiedler Ute , Floridi Piero , Gros‐Dagnac Helene , Hensch Tilman , Hoffmann Karl‐Titus , Kuijer Joost , Lopes Renaud , Marra Camillo , Müller Bernhard W. , Nobili Flavio , Parnetti Lucilla , Payoux Pierre , Picco Agnese , Ranjeva Jean‐Philippe , Roccatagliata Luca , Rossini Paolo Maria , Salvatore Marco , Schonknecht Peter , Schott Björn H , Sein Julien , Soricelli Andrea , Tarducci Roberto , Tsolaki Magda , Visser Pieter Jelle , Wiltfang Jens , Richardson Jill , Frisoni Giovanni B , Marizzoni Moira , Consortium PharmaCog 
Published: December 2020

AbstractBackgroundThe amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behaviour but their small size hampers their manual segmentation in multicenter datasets. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors. We applied a new high‐resolution atlas in two independent cohorts of older and younger healthy adults.MethodSixty‐four older (PharmaCog study; age range: 50‐78 years) and 67 younger subjects (CoRR consortium; age range: 18‐43 years) underwent repeated 3D‐T1 MRI at two different time points between 1 and 90 days. Amygdala and hippocampus segmentation was performed using FreeSurfer v6.0. Reliability of functional parcellations was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. Nuclei/subfields were considered as single structures and grouped into relevant subregions (for the amygdala, basolateral and the centromedial complexes; for the hippocampus, head, body, and tail subdivisions).ResultDifferences in MRI site/vendor had a significant impact (p<.05) for the ε of few subfields/nuclei, while extensively impacted DICE of most structures. The effect on DICE was limited by the functional parcellation only in the younger cohort. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (|rs|>.43, p<.001). In line, nuclei larger than 200 mm3 and subfields larger than 300 mm3 (except for molecular layer) had the best test‐retest reproducibility (ε<5% and DICE>0.80).ConclusionOur results support the use of volumetric measures derived automatically from larger amygdalar nuclei and hippocampal subfields as reliable measures in multisite longitudinal MRI studies. These measures could be useful for studies evaluating disease progression and treatment response.
Acute vascular dementia with bi‐thalamic infarction due to the artery of Percheron occlusion
Authors: Suen Mengfan , Zhang Qian , Chen Qidong , Xu Jun 
Published: December 2020

AbstractBackgroundPrevious studies reported the altered mental status and behavioral amnesic impairment were the dominated clinical findings in patients with bi‐thalamic paramedian infarction only due to the occlusion of the artery of Percheron(AOP). However, the clinical features of multidomain cognitive impairment because of bi‐thalamic paramedian infarction need to be clarified.MethodWe report a 72 year old male with a history of hypertension who presented an acute vascular dementia with a multidomain cognitive impairment including memory, attention, orientation. Laboratory test results were not remarkable. Brain magnetic resonance imaging (MRI) revealed a bi‐thalamic symmetrical paramedian infarction. Large arterial computed tomography angiography (CTA) showed the thinner right vertebrobasilar artery and atherosclerotic plaques in the beginning of both internal carotid arteries and the right subclavain artery. Transthoratic echocardiograp‐ ‐hy revealed left ventricular diaslolic dysfunction with ejection fraction of 60%. 24‐hour dynamic eletrocardiogram(Holter) revealed paroxymol atrial tachycardia. However, there was no evidence of cardioembolism.ResultThe diagnosis of cerebral infarction that causes vascular dementia with a presumed occlusion of the artery of Percheron resulting from atherosclerosis was made and the treatment of antiplatelate and improving cognition was provided.ConclusionThis case illustrates vascular dementia resulting from bi‐thalamic paramedian infarction deserves clinical attention.