bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence exclusive labels in cognitive research cause unstable prevalence estimates over time
Authors: Richardson Connor Duncan , Stephan Blossom CM , Robinson Louise , Brayne Carol , Matthews Fiona E , Function Cognitive , Studies Ageing 
Published: December 2021

AbstractBackgroundWhile age specific prevalence of dementia has recently declined in some high‐income countries it is unclear whether or how the milder end of the spectrum, including Mild Cognitive Impairment might also have changed across generations. This is likely to vary according to how cognitive impairment has been defined, including exclusion criteria. Previous findings from the Cognitive Function and Ageing Studies (CFAS) show prevalence of mild impairment has either increased or remained stable depending on the criteria used, while more severe impairment has decreased over time. Whether different subtypes of MCI used in contemporary studies have different time trends are not known.MethodData are from the English sites of the population representative Cognitive Function and Ageing Studies (CFAS). In 1991 7,635 participants were interviewed in CFAS I in Cambridgeshire, Nottingham and Newcastle with 1457 being diagnostically assessed. In the same geographical areas, the CFAS II investigators interviewed 7,796 individuals in 2011. Using consensus criteria, the population was categorised into MCI and ‘other cognitive impairment no dementia’ OCIND. Each cognitive group was further subtyped by the domain of cognition into amnestic (aMCI and aOCIND), non‐amnestic (naMCI and naOCIND) and multi‐domain (mMCI and mOCIND) groups, memory complaints were included as an OCIND subtype. Prevalence estimates for each were calculated using multinomial logistic regression, adjusted for age, sex and education. Results were standardized to the age‐sex specific UK and global population.ResultBetween 1991 and 2011 naMCI declined substantially (10.5% versus 6.3%), mMCI increased very slightly (5.9% versus 6.3%) while aMCI, whilst relatively rare, more than doubled in prevalence (1.2% versus 2.6%). In terms of OCIND, the prevalence of naOCIND has dropped (from 17.6% to 13.9%), aOCIND has increased (3.8% to 4.9%) while mOCIND has more than doubled (from 5.7% to 11.2%).ConclusionBetween 1991 and 2011 naMCI declined substantially (10.5% versus 6.3%), mMCI increased very slightly (5.9% versus 6.3%) while aMCI, whilst relatively rare, more than doubled in prevalence (1.2% versus 2.6%). In terms of OCIND, the prevalence of naOCIND has dropped (from 17.6% to 13.9%), aOCIND has increased (3.8% to 4.9%) while mOCIND has more than doubled (from 5.7% to 11.2%).
The NeuroMET project: Metrology and innovation for early diagnosis and accurate stratification of patients with neurodegenerative diseases
Authors: Quaglia Milena , Cano Stefan , Fillmer Ariane , Flöel Agnes , Giangrande Chiara , Göschel Laura , Lehmann Sylvain , Melin Jeanette , Teunissen Charlotte E. 
Published: December 2021

AbstractBackgroundThe NeuroMET project aims are to develop: 1) a “NeuroMET memory metric” metrologically validated with clinical laboratory data that will be implemented into a app for delivery of cognitive tests 2) 7T magnetic resonance imaging and spectroscopy protocols and measurement uncertainty frameworks to be implemented into clinic and applied to larger studies; 3) reference measurement procedures and liquid chromatography based methods for t‐tau; p‐tau; α‐synuclein, NF‐L to underpin standardisation initiatives; 4) new clinical methods for quantification of synucleins and differentiation of synucleopathies for subsequent validation with support from the metrological infrastructure; and 5) construct specification equations to serve as reference for memory task difficulty and person memory abilityMethodMultiple approaches: LC‐MS and GC‐MS from different manufactures; 7 and 3 Tesla MRI and MRS (Siemens); RT‐QUIC; immunoassays (Simoa, MSD and Eurimmune); Rasch Measurement Theory analysis and principal component regression. All data are acquired for healthy controls, subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease patients recruited at Charitè.Result1) The most promising memory test items from legacy cognitive assessments data (focussing on blocks, numbers and word lists) from the NeuroMET patient cohort were selected to be used for the development of the NeuroMET Memory Metric. Construct specification equations were developed to serve as reference for memory task difficulty and person memory. 2) 7 T MRI and MRS protocols were developed. Those are applied to the project cohort and a framework for the definition and improvement of measurement uncertainty is designed. 3) A t‐tau primary calibrator characterization was finalized and the material shared with the IFCC‐CSF WG to be used for a round robin study. 4) A α‐synuclein reference measurement procedure was finalized and a hydrogen deuterium exchange mass spectrometry method developed to monitor the stability of the protein in different solvents and storage conditions. This methods will underpin the development of a liquid chromatography mass spectrometry method and a RT_QUIC method for synucleopathiesConclusionMultidisciplinary reference methods and frameworks for the definition of measurement uncertainty to be applied to facilitate uptake of new technology, to underpin the definition of clinical thresholds and ultimately to enable early diagnosis and patient stratification
Sex‐differences in neural responses to experimental pain in Alzheimer's disease
Authors: Failla Michelle D , Iversen Wm. Larkin , Atalla Sebastian W , Cowan Ronald L , Monroe Todd B 
Published: December 2021

AbstractBackgroundPeople with Alzheimer’s disease (AD) generally receive less analgesic medications and verbally report pain less frequently than age‐matched healthy controls (Scherder 2005). Studies have also shown that people with AD exhibit differences in neural responses to acute experimental pain relative to controls (Monroe 2017). Several studies demonstrate that women report more pain than men and are at a greater risk for mismanagement of pain irrespective of cognitive status (Fillingim 2009). Thus, this study aimed to investigate sex differences in the neurophysiological response (fMRI) to experimental thermal pain in people with AD when compared to controls. We hypothesized that women with AD would have increased activation in brain regions related to the cognitive and emotional processing of pain.MethodThe sample consisted of 73 adults (age 65‐97), 36 adults with AD and 37 adults in a healthy control comparison group. In this study, 52.05% of the participants were female, matched across age and AD status. Experimental thermal perceptions for mild and moderate pain were collected prior to scanning. Stimuli were applied to the thenar eminence of the right hand. During fMRI, percepts were passively delivered during four runs, trials included 16 seconds of stimulus with 24 seconds of rest. Whole brain analysis for a sex by diagnostic group interaction was explored mild and moderate pain conditions. Standard SPM12 approaches were used for all analyses.ResultWe found significant main effects of both AD and sex in each pain condition indicating significant differences in brain activation for both males and females with AD compared to male and female controls (all p’s < 0.05), however there was no significant sex by AD group interaction in either contrast comparison.ConclusionWhile there are significant effects of both sex and AD on neural responses to pain, there was no significant evidence of a unique effect of sex on neural responses in AD. This work suggests that differences in pain responses by sex is relevant to consider in addition to disease specific effects. Sex differences seen in healthy cohorts may not persist to the same degree the Alzheimer’s disease brain.
Theracurmin may be a therapeutic option for elderly patients with Alzheimer’s disease: A 6‐month retrospective follow‐up study
Authors: Dost Fatma Sena , Kaya Derya , Erken Neziha , Bulut Esra Ateş , Ontan Mehmet Selman , Aydın Ali Ekrem , Isik Ahmet Turan 
Published: December 2021

AbstractBackgroundTherapeutic options for Alzheimer’s Disease (AD) treatment are highly limited and success rate in new molecules under investigated has been disappointing so that agents with various mechanisms represent a promising therapeutic opportunity. Among these, Theracurmin, a very highly absorbable curcumin formulation, was shown to improve memory and attention in non‐demented people. We aimed to investigate the effect of Theracurmin on the disease course in elderly patients with mild cognitive impairment (MCI) and AD.MethodThis is a retrospective follow up study on 93 consecutive elderly patients with MCI or AD. All patients underwent Comprehensive geriatric assessment (CGA), including Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), clock‐drawing test, trail making, activities of daily living (ADL), at baseline and end of the sixth month. Nineteen of 52 patients with AD and 17 of 41 patients with MCI were treated with Theracurmin 180 mg/day (PO). All AD patients were also treated with an acetylcholinesterase inhibitor.ResultDuring the follow up period it was observed that MMSE or MOCA and instrumental ADL (IADL) scores declined in AD patients without treating with Theracurmin (p=0.001; 0.011; 0.004, respectively), whereas these scores remained stable in those with Theracurmin. Furthermore, this stabilization in the IADL was also observed in MCI patients treated with Theracurmin, but not in those without Theracurmin. During the follow‐up, three of MCI patients who did not receive Theracurmin progressed to AD, whereas it was only one patient in those who received it. No discontinuation of Theracurmin therapy was observed.ConclusionTheracurmin seems to be a therapeutic option for elderly patients with AD and MCI because of providing stabilization of the disease course by preventing progressive loss in cognitive functions and ADLs. Further prospective, multicenter, community‐based studies are needed to confirm these promising findings.
CSF protein panels reflecting multiple pathophysiological mechanisms for early and specific diagnosis of Alzheimer’s disease
Authors: Campo Marta Del , Peeters Carel F.W. , Johnson Erik C.B. , Vermunt Lisa , Hok‐A‐Hin Yanaika S. , van Nee Mirrelijn , Chen‐Plotkin Alice , Hu William T. , Lah James J. , Seyfried Nicholas T. , Herradon Gonzalo , Meeter Lieke H.H. , van Swieten John C. , Levey Allan I. , Lemstra Afina W. , Pijnenburg Yolande A.L. , Visser Pieter Jelle , Tijms Betty M. , van der Flier Wiesje M , Teunissen Charlotte E. 
Published: December 2021

AbstractBackgroundThe development of disease‐modifying therapies against Alzheimer’s disease (AD) requires biomarker panels that reflect the diverse pathological pathways specifically involved in AD. Here we aimed to identify and validate panels of cerebrospinal fluid (CSF) proteins covering different molecular pathways for early and specific diagnosis of AD.MethodWe measured 665 proteins in 797 CSF samples from patients with mild cognitive impairment with abnormal amyloid (MCI(Aβ+): n=50), AD‐dementia (n=230), non‐AD dementias (n=322; 123 DLB and 199 FTD) and cognitively‐unimpaired controls (n=195; classical AD CSF biomarkers negative) using proximity ligation‐based multiplex immunoassays. Nested and penalized linear modeling were used to identify protein differences (q<0,05) and translatable classification signatures.ResultWe detected highly dysregulated CSF proteins in MCI(Aβ+) or AD compared to controls (112 and 288 proteins respectively, lowest q:1‐15 and 1‐23), as well as between AD and non‐AD dementias (469 proteins; lowest q:1‐29). We confirmed previous findings (e.g., DDAH1, ENO2, PARK7), but we also identified novel proteins especially associated to the prodromal and/or dementia AD stages (e.g., ABL1, SCD4, ENTPD5). Proteins dysregulated in MCI(Aβ+) were primarily related to oxidative stress and energy metabolism, while those specifically dysregulated in later stages of AD dementia were related to cell remodeling, vascular function and immune system. Using penalised generalised linear modeling we identified the minimal number of markers with maximal power to discriminate clinical groups: for MCI(Aβ+) vs. controls: 10‐CSF proteins, AUC:0.99 (95%CI:0.97‐1); for AD vs. controls: 8‐CSF proteins, AUC:0.95 (95%CI:0.92‐0.99) and for AD vs. non‐AD dementias: 9‐CSF proteins, AUC:0.87 (95%CI:0.81‐0.93). The CSF panel discriminating AD from cognitively unimpaired controls was validated in an independent external cohort (n=62, AUC:0.94). Only 3 proteins overlapped across panels, suggesting that the panels with the strongest discriminative power are specific for disease stage and clinical group.ConclusionThis unprecedented large and protein‐rich CSF study indicates that CSF proteome follows a highly dynamic trajectory with distinct CSF profiles associated to different biological processes along the AD continuum. We unveil optimal CSF biomarker panels reflecting the specific multifactorial nature of AD, which can be now translated into customised assays for widespread validation and potential use in heterogeneous diagnostic settings or clinical trials.
Complementary analyses of the AMBAR trial: Individual items of CDR and ADAS‐Cog12 in Alzheimer’s disease patients treated with plasma exchange with albumin replacement
Authors: Nicodemus‐Johnson Jessie , Hendrix Suzanne B. , Barceló Miquel , Boada Mercè , Lopez Oscar L. , Núñez Laura , Grifols Carlota , Páez Antonio 
Published: December 2021

AbstractBackgroundAMBAR (Alzheimer’s Management By Albumin Replacement) study results demonstrated that plasma exchange and albumin replacement (PE‐A) with or without intravenous immunoglobulin slows the progression of Alzheimer’s disease (AD) as measured by cognitive (ADAS‐Cog12), functional (ADCS‐ADL), and global assessment (CDR) (Boada et al. Alzheimers Dement 2020;16:1412). In this complementary analysis, we explored the association of ADAS‐Cog12 and CDR subdomains with treatment effects overall as well as stratified by AD severity.MethodAD patients (N=347) were randomized (1:1:1:1) to one of the three different PE‐A treatments or placebo (sham PE‐A). We analyzed the performance of active (all 3 PE‐A‐treated groups) relative to placebo overall as well as stratified by AD severity for each of the 6 domains of CDR scale and 12 items of ADAS‐Cog12 grouped in three categories of “Memory”, “Language” and “Praxis” (Verna et al. Alzheimer Res Ther 2015;7:64). Language was also assessed through Phonetic and Semantic Verbal Fluency (PVF, SVF) tests and Neuropsychological Assessment Battery (NAB) naming test. Changes from baseline were analyzed using a mixed model for repeated measures (MMRM).ResultPE‐A‐treated patients showed improvement by month 14 (p<0.05) in 5 of 6 CDR domains (“Memory”; “Orientation”; “Judgement & Problem solving”; “Home & Hobbies”; “Personal care”), with effect sizes from 71% (less decline) to >100% (improvement over baseline). The “Community affairs” domain had borderline significance (p=0.08). PE‐A‐treated moderate AD patients (MMSE: 18‐21) exhibited improvement over control whereas PE‐A‐treated mild AD patients (MMSE: 22‐26) were not significantly different. Among ADAS‐Cog12 items, PE‐A‐treated patients showed improvement by month 12 or 14 (p<0.05) in at least one of the categories “Language”, “Memory” or “Praxis” with effect sizes from 76 to >100%. PVF and SVF also demonstrated improvements by month 14 (all effect sizes >100%; p‐values: 0.003‐0.04). For the stratified analysis, this improvement, favoring PE‐A‐treated individuals, was only observed in the mild AD group (p= 0.0040 [PVF] and 0.02 [SVF]). Finally, NAB demonstrated improvement by 12 months only in the moderate group (p=0.04).ConclusionPE‐A demonstrated beneficial effects across all CDR domains and language tests, while the ADAS‐Cog12 benefit may be more prominent in specific subdomains of memory, language and praxis.
Physiotherapy with dual task improves cognition in Parkinson’s disease with postural instability and gait disorders
Authors: Leocadi Michela , Canu Elisa , Sarasso Elisabetta , Gardoni Andrea , Castelnovo Veronica , Piramide Noemi , Volonté Maria Antonietta , Filippi Massimo , Agosta Federica 
Published: December 2021

AbstractBackgroundPrevious studies suggested that action observation training (AOT) and motor imagery (MI) improve motor learning in Parkinson’s disease (PD) patients. The aim of this study was to assess cognitive changes following a 6‐week training associated with dual‐task gait/balance exercises in PD patients with postural instability and gait disorders (PD‐PIGD).Method25 PD‐PIGD patients were randomized into 2 groups: i) AOT‐MI+DUAL‐TASK group performed a 6‐week (W6) training consisting of AOT‐MI combined with practicing observed‐imagined gait and balance exercises; ii) DUAL‐TASK‐group performed the same exercises combined with landscape‐videos observation. At baseline, W6 and W14 patients underwent neurological, computerized cognitive and motor evaluations. A group of 23 healthy controls (HC) underwent a neuropsychological assessment at the study entry only. Cognitive changes in patients were monitored with the CANTAB (Cambridge Neuropsychological Test Automated Battery). Cognitive changes at each time point in the overall PD‐PIGD sample and between groups (AOT‐MI + DUAL‐TASK and DUAL‐TASK) were assessed.ResultAt baseline, no cognitive differences were found between the two PD‐PIGD groups. However, both PD groups performed worse than HC in several cognitive domains. Over time, both PD groups improved in terms of gait velocity and balance. Regarding cognitive changes, at W6 and at W14, all PD patients improved in terms of accuracy and reaction times in tests assessing attention switching and visuospatial localization abilities. No differences were observed between groups over time.ConclusionA physiotherapy approach associated with dual‐task gait/balance exercises can improve cognitive performances in PD‐PIGD patients that persist at long term. This improvement is evident in specific cognitive domains, which are usually affected in PD‐PIGD and can interfere with their motor performances.
Premorbid personality in frontotemporal dementia: Amyotrophic lateral sclerosis spectrum
Authors: Vinceti Giulia , Gallingani Chiara , Fiondella Luigi , Carbone Chiara , Salemme Simone , Tondelli Manuela , Martinelli Ilaria , Zucchi Elisabetta , Mandrioli Jessica , Chiari Annalisa , Zamboni Giovanna 
Published: December 2021

AbstractBackgroundFrontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are considered two clinical expressions of the same neurodegenerative continuum (FTD‐ALS spectrum) with common underlying pathology and genetics. Patients can present with pure behavioral/cognitive (FTD), pure motor (ALS) or mixed (FTD‐ALS) forms. The factors determining the development of one rather than the other phenotype are unknown. However, it is common observation that patients’ personality traits differ between the phenotypes: ALS patients tend to display a prosocial behavior characterized by kindness and agreeableness. On the opposite, FTD patients frequently present with disinhibition, anti‐social behaviors and lack of empathy. These traits are often described by patients’ relatives as having always characterized the patients’ personality. We therefore aimed at testing if FTD and ALS patients have different premorbid personalities, under the hypothesis that they reflect different vulnerabilities in the brain circuits related to social behavior and motor function, respectively.MethodWe prospectively recruited the patients presenting to our Memory and Motor Neuron Disease Clinics between December 2018‐December 2020. Patients’ personality was assessed through the NEO Personality Inventory 3 (NEO‐PI‐3), which analyses the five main personality factors (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness). NEO‐PI‐3 was administered to patients’ caregivers with reference to the patient’s personality at two timepoints: at diagnosis and 15 years prior to symptoms onset. Differences in personality factors between groups at each timepoint were tested with ANOVA.Result46 consecutive patients (30 FTD, 13 ALS, and 3 FTD‐ALS assigned to the FTD or ALS group, based on their first symptom) were recruited. A significant difference in premorbid personality emerged in the Openness domain, showing that ALS patients (mean value 153±15) had been more open to new experience, ideas and emotions than FTD patients (132±21 ‐ p=0.049), even many years before symptoms onset. Such difference in Openness was decreased at the current moment but persisted (147±16 vs 123±24, p= 0.06).Conclusionwe found that premorbid personality profile differed in FTD and ALS patients in at least one personality domain (Openness), supporting the hypothesis that premorbid personality may represent a vulnerability marker to the development of behavioral or motor disturbances. Our finding needs to be further explored with imaging.
Patient attitudes towards remote memory clinic assessment
Authors: Blane Jasmine , ClareO'Donoghue M , Craig Emma , Clarke Laura , Raymont Vanessa , Mackay Clare , Martos Lola 
Published: December 2021

AbstractBackgroundDue to demand on UK memory clinic services, most patients have limited consultant interaction before diagnosis/discharge. Technology offers an opportunity for remote assessment, from telephone/video‐based consultations to fully digitised cognitive assessments with potential to track disease progression. Whilst many acute services utilise remote assessment, there are perceived barriers in memory clinic populations. However, COVID‐19 and related national restrictions may have altered patients’ attitudes towards and experience with remote assessment tools. We aimed to investigate attitudes including confidence and perceived challenges towards remote assessment as well as access and experience with technology amongst Oxfordshire memory clinic patients.MethodBetween June and September 2020, all patients awaiting initial memory clinic assessment were asked to participate in a standardised semi‐quantitative survey as part of an Oxford Health NHS Foundation Trust service evaluation. Designed with service‐user input, questions aimed to capture availability, experience and confidence using technology and patients’ comfort with assessment, diagnosis and future care discussions being conducted remotely, as well as any concerns or comments.ResultAmongst 73 respondents (average age=79.1 years), access to technology was high; 82% reported telephone access and 58% to a laptop, tablet, smartphone or combination of the three. 17% reported previous use of web‐based video conferencing tools, and although confidence using these tools was 7%, this increased with written instruction or relative assistance. Similarly, whilst under half of the respondents felt comfortable with assessments, diagnosis or future care discussions occurring remotely, this increased to approximately two thirds with relative presence (67%, 69% and 66%, respectively). Qualitative analysis of patient’s comments regarding remote assessment also revealed concerns over wait times/urgent need for assessment. However, 62% preferred to wait for an in‐person visit, rather than an immediate remote appointment.ConclusionThis survey demonstrates availability of technology in this population but a disparity in willingness to engage in remote assessment. Consequently, there is a need to diverge from one‐size‐fits‐all models to a tiered approach that helps facilitate individual choice based on the availability/confidence with technology and level of relative support. The Oxford Brain Health Centre, an integrated clinical‐research service, provides an opportunity to research this tiered approach in clinical practice.