bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic inequalities in cognitive function in midlife and early late‐life are partially attributable to modifiable health and lifestyle factors
Authors: Roehr Susanne , Pabst Alexander , Witte A Veronica , Schroeter Matthias L , Loeffler Markus , Villringer Arno , Riedel‐Heller Steffi G 
Published: December 2020

AbstractBackgroundThere are socioeconomic inequalities in dementia risk. Growing evidence highlights the prevention potential of dementia through modifiable health and lifestyle factors. We aimed to investigate whether health and lifestyle factors play a mediating role in the association of socioeconomic inequalities and cognitive function in midlife and early late life in the general population.MethodThe “LIfestyle for BRAin health” (LIBRA) score was computed for 6.203 baseline participants of the LIFE‐Adult study, a population‐based cohort to investigate civilization diseases in the German population. LIBRA is a validated score (range: ‐5.9 to +12.7) that predicts dementia in midlife and early late life, consisting of twelve modifiable health and lifestyle factors (heart disease, kidney disease, diabetes, obesity, hypertension, hypercholesterolemia, alcohol consumption, smoking, physical inactivity, diet, depression, cognitive activity). Socioeconomic status (SES; low/middle/high) was calculated based on education, net equivalence income, and occupational status. We used structural equation modelling to inspect potential mediation of the LIBRA score between SES and measures of cognitive function (Verbal Fluency Test/VFT; Trail Making Test/TMT A and B). Analyses were adjusted for age, sex, marital status, living situation, employment, and social network.ResultParticipants were M = 57.7 (SD = 12.0, range: 40‐79) years old and dementia‐free; 50.7% were female. Individuals with low SES had significantly higher LIBRA scores (indicating higher dementia risk) compared to individuals with middle SES and high SES, who had the lowest LIBRA scores (M = 1.2, SD = 2.3 vs. M = ‐0.4, SD = ‐2.6 vs. M = ‐1.2, SD = 2.5; F(2) = 271.8, p < .001). Likewise, all neuropsychological test scores showed that cognitive function was lowest in individuals with low SES and highest in individuals with high SES. Bootstrapped mediation analysis indicated that 12.4% (VFT) to 22.8% (TMT) of the differences in cognitive function between low SES and high SES were significantly mediated by differences in LIBRA scores.ConclusionDifferences in cognitive function due to socioeconomic inequalities can be partially attributed to differences in modifiable health and lifestyle factors. Thus, promoting health and lifestyle changes in individuals with low SES could contribute to attenuate socioeconomic inequalities in cognitive function, potentially benefiting dementia prevention.
Sex differences in subcortical aging: A nomogram study of age, sex, and apoe (N = 9,414)
Authors: Ching Christopher , Abaryan Zvart , Santhalingam Vigneshwaran , Zhu Alyssa , Bright Joanna , Jahanshad Neda , Thompson Paul M 
Published: December 2020

AbstractBackgroundCommon variants in the APOE gene are associated with cognitive decline, brain atrophy and risk for developing Alzheimer’s disease (AD). APOE polymorphism effects may also vary with age, sex, body mass index (BMI), and other risk factors. Here we create percentile charts ‐ or ‘nomograms’ ‐ plotting the trajectory of subcortical volumes with age, stratified by sex and by APOE genotype, in a large population‐based sample from the UK Biobank. We hypothesized that age effects would differ in men and women and APOE e4 allele carriers would tend to show steeper age‐related decline compared to those carrying APOE e3 and e2 genotypes.MethodT1‐weighted brain MRI UK Biobank data (N=9,414; age range: 44‐79 yrs (Table 1) were processed using FreeSurfer v5.3 to derive quality inspected volumes averaged across hemispheres: lateral ventricles, hippocampus, thalamus, putamen, pallidum, amygdala, caudate, nucleus accumbens, and intracranial volume (ICV). The R package rstandard was used to adjust subcortical volumes for effects of ICV and BMI. R package GAMLSS, specifically the centile function, was used to compute percentile curves for each ROI based on standardized residuals, with ROI volume as the dependent variable and age as the independent variable. Separate models were fitted by sex and for each APOE genotype and visualized for trends with age.ResultNomograms for the full cohort showed trends for increasing lateral ventricle and decreasing thalamus, putamen, hippocampus, amygdala, and nucleus accumbens volumes with increasing age (Figures 1‐2). In men, volumes decreased at a faster rate until age 60, when volumetric decline in women appeared to accelerate and catch up with males. Nomograms separated by APOE genotype (Figure 1) all followed similar patterns, though smaller samples of APOE e2/2 and e4/4 genotypes limit the interpretability of those age trends.ConclusionNomograms plotted by sex show a differential age trajectory for men and women offering clues for future sex‐dependent brain related assessment and intervention. APOE genotype did not strongly influence nomograms, though a greater number of APOE e2/2 and e4/4 individuals are needed to obtain reliable normative trends.
The Aβ42/Aβ40 ratio in plasma is associated with amyloid‐PET status and rate of progression in individuals with subjective cognitive decline: The Fundació ACE Healthy Brain Initiative
Authors: de Rojas Itziar , Fandos Noelia , Romero Judith , Pesini Pedro , Marquié Marta , Tartari Juan Pablo , Sanabria Angela , Sotolongo‐Grau Oscar , Ruiz Agustin , Boada Mercè , Sarasa Manuel ,   the FACEHBI study group
Published: December 2020

AbstractBackgroundCumulative data suggest that subjective cognitive decline (SCD) could be an early clinical manifestation of Alzheimer’s disease (AD). The performance of blood based AD‐related biomarkers at this early stage of the disease continuum has not been sufficiently studied yet.MethodWe explored the association between total Aβ42 to total Aβ40 ratio in plasma (TP42/40) assessed by ABtest (Araclon Biotech) and cortical β‐amyloid assessed by Florbetaben positron emission tomography (FBB‐PET, Life Molecular Imaging) scan in 162 cases of SCD from the Fundació ACE Healthy Brain Initiative (FACEHBI) with plasma and FBB‐PET data at baseline (V0) and two years follow‐up (V2) visits. All plasma samples were analyzed simultaneously at the time of V2. Cut‐off for PET‐FBB positivity was established at a global standardized uptake volume ratio (SUVR)>1.45.ResultTP42/40 was significantly lower in FBB‐PET‐ve) than in FBB‐PET+ve group at both time points (Mann‐Whitney test P<0.0001). The AUC in the ROC analysis for the relevant demographic variables (age and APOE genotype) to discriminate FBB‐PET status at V0 and V2 was 80% and 83%, respectively. Those values increased significantly (P<0.01) up to 90% and 92%, respectively, when TP42/40 was included as a predictive variable within the model. The performance parameters of TP42/40 to discriminate FBB‐PET status in V0∼V2 were SEN 1.0∼0.94, SPE 0.49∼0.42, PPV 0.16∼0.15 and NPV 1.0∼0.98, respectively. Caution should be exerted when interpreting these values because they could be biased given the very low prevalence of FBB‐PET+ve (8.6%) in this early population, at the current SUVR cut‐off. Nevertheless, in a recruiting scenario targeting FBB‐PET+ve individuals with SCD, a pre‐screening step based on TP42/40 could save 46%∼34% of PET scans. Furthermore, those individuals with a TP42/40 ratio in the lowest quartile at V0 showed significantly (P<0.01) greater increases of FBB‐PET SUVR at V2 than those with a V0 plasma ratio in the two upper quartiles.ConclusionTP42/40 is consistently associated with cortical β‐amyloid burden assessed by FBB‐PET in individuals with SCD. The TP42/40 could be a useful tool helping in the recruitment of SCD individuals with preclinical Alzheimer’s.
The Barcelonabeta dementia prevention research clinic: Study design, recruitment profiles and inclusion in prevention studies — An update
Authors: Fauria Karine , Minguillón Carolina , Félez‐Sánchez Marta , Menezes‐Cabral Sofia , Sánchez‐Benavides Gonzalo , Grau‐Rivera Oriol , Gispert Juan Domingo , Molinuevo Jose Luis 
Published: December 2020

AbstractBackgroundUp to 40% new patients in memory clinics complain of worse cognitive performance scoring within normal ranges in cognitive tests, hence presenting what is termed ‘subjective cognitive decline’ (SCD). Although usually dismissed, they present an increased progression rate to mild cognitive impairment (MCI) and dementia. There is, therefore, an emergent need for newly designed programs to provide individual risk estimates and tailored risk‐reduction plans. With the aim of assessing the emotional impact and cost‐benefit of these programs, we established the BarcelonaBeta Dementia Prevention Research Clinic (BBDPRC).MethodA longitudinal, prospective study of 400 participants (60‐80 years) with SCD or MCI was set‐up. General population participants concerned about their cognitive performance were pre‐selected by their replies to web‐based forms capturing information about their subjective cognitive performance. Those selected undergo baseline visit for (1) diagnosis, (2) collecting data to enable the estimation of a dementia risk score and (3) produce their personalised prevention action plan. At the subsequent visit, their risk estimates are disclosed and personalised primary prevention advice presented. Individuals with MCI are readily offered to enter studies/trials they may benefit from. The emotional impact of disclosure is measured at 1 and 6 weeks and 6 and 12 months post‐disclosure. At 6‐weeks, SCD participants are offered to enter suitable prevention studies (Fig.1). A cost‐benefit analysis of this program will also be performed using standard methods.ResultBBDPRC was presented in a press‐conference. 1,633 persons registered on the website and >50% of them were classified by an embedded algorithm as a priori eligible (Fig.2). To date, ∼300 persons (First‐Patient‐In 16/7/2018) have undergone baseline visit (screening failure 6.5%). From the ones with disclosed diagnosis, 18.5% were MCI, 55.0% SCDplus (fulfilling >3 SCDplus features) and 26.5% SCD. 52.9% of these participants comply with eligibility criteria with ongoing studies at BBRC and, remarkably, 69.9% were included in the studies proposed (Fig.3).ConclusionWe have established a web‐based registry that is proving to be very efficient in recruiting SCDplus or MCI individuals being more than half suited for dementia prevention studies and trials. Furthermore, this infrastructure sets the basis for future personalised approaches.
Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to motor visual hallucinations in patients with Parkinson’s and Lewy body diseases
Authors: Lopez Susanna , Percio Claudio Del , Pascarelli Maria Teresa , Lizio Roberta , Noce Giuseppe , Ferri Raffaele , Soricelli Andrea , Nobili Flavio Mariano , Arnaldi Dario , Famà Francesco , Bonanni Laura , Franciotti Raffaella , Onofrj Marco , Fuhr Peter , Gschwandtner Ute , Ransmayr Gerhard , Aarsland Dag , Parnetti Lucilla , Farotti Lucia , Marizzoni Moira , D'Antonio Fabrizia , de Lena Carlo , Güntekin Bahar , Hanoğlu Lutfu , Yener Görsev , Emek‐Savas Derya Durusu , Triggiani Antonio Ivano , Taylor John‐Paul , McKeith Ian , Stocchi Fabrizio , Vacca Laura , Hampel Harald , Frisoni Giovanni B , Pandis Maria Francesca , Babiloni Claudio 
Published: December 2020

AbstractBackgroundParkinson’s disease (PD) is the second‐most common neurodegenerative disorder that affects 2–3% of the population ≥ 65 years of age and may belong to cognitive deficits and dementia in 50% of cases. Disease with Lewy Bodies (DLB) is emerging as another important cause of dementia in pathological aging. PD and DLB are both due to intra‐neuronal Lewy bodies and are characterized not only by motor dysfunctions but also by cognitive and/or psychiatric symptoms. An open issue is the extent to which these diseases are distinct entities. In this respect, here we compared cortical sources of resting state eyes‐closed electroencephalographic (rsEEG) rhythms in PD and DLB patients having visual hallucinations.MethodClinical and rsEEG rhythms in demographic matched PD (N = 93), DLB (N = 46), Alzheimer’s disease dementia (AD, N= 70) and healthy elderly (Nold, N = 60) subjects were available from an international archive. Pathological groups were matched for cognitive status. Individual alpha frequency peak was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were considered. The eLORETA freeware estimated rsEEG cortical sources.ResultAs a confirmation of previous studies, compared to the Nold subjects, the AD, LBD, and PD patients showed higher widespread delta source activities and lower posterior alpha source activities. Specifically, posterior alpha source activities were more abnormal in the AD than the LBD and PD groups, while widespread delta source activities were more abnormal in the PD and DLB than the AD group. As novel results, in relation to the LBD and PD patients without visual hallucinations and the control groups (Nold, AD), those with visual hallucinations were characterized by higher parietal delta source activities (LBD, Figure 1) and parieto‐occipital alpha sources activities (PD, Figure 2).ConclusionThese novel results suggest that in LBD and PD patients resting in the quiet wakefulness, abnormalities in cortical neural synchronization at delta and alpha frequencies in parietal cortex are differently related to visual hallucinations despite the essence of alpha‐synucleinopathy.
Association of Alzheimer's disease and amyotrophic lateral sclerosis: A series of cases and review of the literature
Authors: Vrillon Agathe , Deramecourt Vincent , Pasquier Florence , Wallon David , Lozeron Pierre , Amar Elodie Bouaziz , Paquet Claire 
Published: December 2020

AbstractBackgroundAmyotrophic lateral sclerosis (ALS) is a sporadic or familial fatal neurodegenerative condition that affects motor neurons in primary motor cortex, brainstem and spinal cord. While predominantly a motor disorder, ALS is frequently associated with cognitive impairment, mostly of frontal type. Hippocampic syndrome is not recognized as part of the cognitive phenotype of ALS.MethodAfter a national translational survey, we report a French multicentric case series of three patients that presented with an association of definite Alzheimer disease (AD) and ALS. A systematic review of the literature was carried out in January 2020 to explore already reported similar cases.ResultPatient n°1 had a history of behavioral variant of AD followed seven years later by onset of bulbar ALS. Cerebro‐Spinal Fluid (CSF) AD biomarkers displayed AD biological profile associated with ApoE4E4 genotype. Genetic testing for C9ORF72 expansion was negative. Patient n° 2 was diagnosed with ALS, associated with dysexecutive syndrome and CSF AD biological profile (Wallon et al, 2012). Patient n°3 had clinical AD and ALS. Post‐mortem analysis was available, confirming motoneuron disease and Alzheimer type pathology. Review of the literature retrieved only few other cases of co‐occurence of AD and ALS (Nijboer et al, 2019; Farid et al, 2015; Müller et al, 1993). More frequently, association of amyloid pathology to ALS lesions at post‐mortem examination has been described in ALS patients with or without cognitive impairment. Nevertheless, the relationship between these findings and clinical manifestations is still unclear. The mechanisms that account for the underlying neurodegenerative processes that occured in our patients remain to be comprehended.ConclusionWe report a series of cases associating AD and ALS and discuss the hypothesis of it being an under recognized phenotype.
Classification of Alzheimer’s disease dementia (ADD) by using features derived from resting‐state electroencephalography (rsEEG)
Authors: Lizio Roberta 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is the most prevalent progressive neurodegenerative disease of the brain affecting the aged people, and the most common cause of dementia (ADD). The actual diagnostic biomarkers of AD are invasive and expensive (e.g., lumbar puncture for CSF sampling; the injection of radioactive tracers in PET procedures). Resting‐state electroencephalography (rsEEG) provide topographic markers useful to assess the neurophysiological changes of the brain that correlate with the cognitive decline and dementia in AD patients.MethodIn this retrospective study, we tested whether the cortical sources of rsEEG rhythms could classify with good performance ADD patients from healthy elderly (Nold) individuals and patients with other diseases. Clinical and rsEEG data of ADD, Parkinson’s disease with dementia (PDD), dementia with Lewy body (DLB), and Nold subjects were available in an international archive. eLORETA estimated the rsEEG cortical sources. Delta, theta, low alpha, high alpha, low beta, high beta, and gamma were the frequency bands of interest. The correct blind classifications (ADD vs Nold, ADD vs PDD, ADD vs DLB individuals) of these rsEEG source activities were performed by GraphPad‐Prism software to produce the receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) provided a measure of how well the rsEEG source activities distinguished the groups (AUC>0.7 as a threshold for a moderate classification rate).ResultsThe posterior delta and alpha sources allowed good classification accuracy (AUC: 0.75‐0.90) in Nold (N=40) vs ADD (N=42), ADD (N=42) vs PDD (N=42), and ADD (N=42) vs DLB (N=38) individuals (Figure.1). We also obtained a good classification accuracy (AUC > 0.80) between the Nold (N = 100) and ADD (N = 100) individuals using bipolar parieto‐occipital delta/alpha and theta/alpha rsEEG features.ConclusionThese results suggest that cortical sources of posterior rsEEG rhythms at different frequency bands and frequency band ratios can be used to discriminate ADD individuals with good performance (AUC>0.8). A single rsEEG marker from a point of care device would provide a cost‐effective, non‐invasive, and repeatable over time biomarker for the assessment of the AD status and progression directly at home.
Psychiatric symptoms in the early detection and differential diagnosis of FTD
Authors: Ducharme Simon 
Published: December 2020

AbstractBackgroundThe early symptoms of behavioral‐variant frontotemporal dementia (bvFTD) have considerable overlap with the common primary psychiatric disorders like major depression and psychotic disorders. Consequently, about 50% are diagnosed with a psychiatric disorder before the identification of bvFTD. While this can be due to inadequate recognition of bvFTD features and lack of expertise, the diagnostic effort is also complicated by the fact that psychiatric symptoms like delusions and hallucinations are sometimes the prodrome to bvFTD—particularly in familial cases. Whereas the reliability of Alzheimer’s disease diagnoses has improved with the advent of molecular biomarkers, the diagnosis of bvFTD remains primarily based on clinical assessment and neuroimaging. The need for a systematic approach to distinguish bvFTD from psychiatric disorders is addressed in recommendations recently developed by an internal panel of experts, the Neuropsychiatric International Consortium for FTD, and are reviewed in this presentation.MethodThe Neuropsychiatric International Consortium for FTD was convened to develop recommendations for a diagnosis approach for identifying bvFTD in individuals with midlife‐onset (>45 years) behavior change. The consensus process included a systematic review of the literature to identify best practices, effective clinical measures and the utility of brain imaging.ResultDifferential diagnosis of bvFTD from psychiatric disorders is facilitated by comprehensive and chronologically‐ordered history, family history of neurodegenerative or neuromuscular disease, use of formal diagnostic criteria for bvFTD and for psychiatric disorders, use of bedside measures of general cognition and social behavior, psychiatric scales and brain imaging. These have been incorporated into an algorithm to facilitate use of the recommendations.ConclusionA systematic approach to the clinical examination can be facilitate the differential of bvFTD from primary psychiatric disorders. This is valuable for providing timely diagnosis, and early counseling and treatment planning to patients, for facilitating testing of novel treatments in clinical trials—and will also facilitate proper treatment for patients with primary and secondary psychiatric states.
Dorsolateral prefrontal cortex metabolites and their relationship with plasticity in Alzheimer’s disease
Authors: Kumar Sanjeev , Iwata Yusuke , Zomorrodi Reza , Blumberger Daniel M. , Fischer Corinne E. , Daskalakis Zafiris J. , Mulsant Benoit H. , Pollock Bruce G. , Graff‐Guerrero Ariel , Rajji Tarek K. 
Published: December 2020

AbstractBackgroundPrevious studies have shown that patients with Alzheimer’s disease (AD) present with deficits in neuroplasticity of their dorsolateral prefrontal cortex (DLPFC); and decreased N‐acetyl aspartate (NAA) and increased myo‐inositol (mI) concentrations in the cingulate cortex and hippocampus. In this study, we examined the relationship between these metabolites and neuroplasticity in the DLPFC of patients with AD and healthy older adults.MethodPatients meeting the core clinical criteria for probable AD and older healthy controls (HC) were recruited. Left DLPFC plasticity was assessed using paired associative stimulation (PAS) combined with EEG. NAA and mI concentrations were assessed in the DLPFC using 3T proton Magnetic Resonance Spectroscopy (point‐resolved spectroscopy, echo time = 35 ms).Result48 AD participants (mean (SD) age: 75.4 (6.9) years; mean (SD) Mini Mental State Examination (MMSE) score (SD): 23.1 (3.1)) were compared with 27 HC (mean (SD) age: 72.3 (7.0) years; mean (SD) MMSE: 29.5 (0.6)): participants with AD had impaired DLPFC plasticity (t = 2.8, df = 69, p = 0.006) and decreased NAA concentration in the DLPFC (t = 2.4, df = 64, p = 0.02). In the combined group of AD and HC participants, after correcting for multiple comparisons, mI concentration in the DLPFC was negatively correlated with DLPFC plasticity (Pearson’s r = ‐ 0.4, n = 62, p corrected = 0.002).ConclusionDeficits in neuroplasticity in the DLPFC of patients with AD are associated with abnormalities of a metabolite indicative of neuronal injury. These findings advance our understanding of potential mechanisms underlying deficits in DLPFC plasticity in AD.