bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volumetric, shape and microstructural alterations of the hippocampal subfields in healthy aging
Authors: Bussy Aurelie , Plitman Eric , Patel Raihaan , Salaciak Alyssa , Farzin Sarah , Bedford Saashi , Béland Marie‐Lise , Tullo Stephanie , Devenyi Gabriel A. , Chakravarty Mallar 
Published: December 2020

AbstractBackgroundAlthough several volumetric studies have attempted to examine the relationship between hippocampal subfields and age, their findings are heterogenous. Here, in addition to typical volumetric measures, we investigated age‐related alterations of hippocampal subfield shape and microstructure.MethodThe present work included 161 healthy participants (ages 18‐81) recruited as part of two local datasets. Standard T1‐weighted (T1w; MPRAGE sequence, 1 mm3 voxels) and high‐resolution T2‐weighted (T2w, 0.64 mm3 voxels) magnetic resonance images were acquired. The minc‐bpipe‐library pipeline (https://github.com/CobraLab/minc‐bpipe‐library) was used to preprocess images. The MAGeT‐Brain algorithm (Pipitone et al., 2014) was utilized for segmentation of the hippocampal subfields (Amaral et al., 2016). The volume and shape (i.e. surface area [SA] and displacement) of the grey matter (GM) subfields (i.e. Cornus Ammonis [CA]1, CA2CA3, CA4 and dentate gyrus [CA4DG], stratum radiatum/lacunosum/moleculare and subiculum) and the volume of associated white matter (WM) regions (i.e. fimbria, fornix, alveus and mammillary bodies [MB]) were estimated using T1w images. Mean T1w/T2w signal intensity ratio (Glasser & Van Essen, 2011) of each subfield was calculated to examine microstructural alterations sensitive to myelin. Linear‐mixed effects models and Akaike information criterion were used to select the most appropriate age relationships from multiple fits (i.e. linear, quadratic, and cubic) for each structure of interest. Sex and ipsilateral hippocampal GM or WM volume were included as covariates. Statistical analyses were performed in R 3.5.0; comparisons surviving p<0.05 (Bonferroni‐corrected) were reported.ResultRight CA1 and alveus volumes were positively cubically related to age and bilateral CA4DG volumes were negatively linearly related to age. T1w/T2w intensity linearly decreased with age for all subregions except for bilateral fornix and MB, which expressed quadratic evolution with age (Figures 1‐2). Age was also inversely related to bilateral SA reduction in the head and medial‐posterior hippocampus, and lateral outward and medial inward displacement (Figure 3).ConclusionThe current work suggests that certain subfields of the hippocampus are more (e.g. CA1) or less (e.g. CA4DG) preserved in healthy aging. These differences do not appear to be explained by microstructural variation.
HCMV infection induces AD pathology in astrocytes in vitro
Authors: Barbian Hannah J. , Lurain Nell S. , Bennett David A. , Al‐Harthi Lena 
Published: December 2020

AbstractBackgroundInfectious agents have long been suspected to be risk factors for Alzheimer’s disease (AD). Some studies have identified a link between neurotropic viruses and AD. While these studies demonstrated an association between AD and neuroviruses, most do not establish a causal link. However, many AD pathological hallmarks, including beta amyloid plaques (Aβ), astrogliosis, neuroinflammation, and neuronal damage, overlap with pathologies caused by neuroviruses. Approximately 80% of adults are seropositive for human cytomegalovirus (HCMV), a virus that is neuroinvasive, productively infects brain cells, and is immune‐dominant in aging populations. Using post‐mortem tissues from the Rush Alzheimer’s Disease Center we previously reported that HCMV infection is associated with AD clinical markers. In the present study, we assessed the ability of HCMV infection to induce two AD pathological hallmarks in astrocytes: Aβ production and astrocyte reactivity.MethodTo determine the impact of HCMV infection on astrocytes, we generated low‐passage clinical HCMV isolates for infection of human fetal astrocytes (HFA) and astroglioma (U251) cells. To assess the ability of HCMV to produce Aβ, we infected HFAs and U251s with HCMV for 3‐9 days then immunostained for Aβ and HCMV proteins. To test whether HCMV infection results in astrocyte reactivity, we infected HFAs with HCMV for 5 days then quantified levels of reactivity‐associated transcripts via quantitative PCR.ResultHFA and U251 infected cells showed HCMV cytopathic effects characteristic of permissive cells, including enlargement and plaque formation. HCMV infection of HFA and U251 cells induced the expression of Aβ as observed by co‐staining of Aβ and HCMV proteins. Aβ production was observed within 3 days and persisted until at least 9 days post‐infection. To assess the amyloidogenicity of HCMV, we employed the Waltz algorithm, which predicted two amyloidogenic sequences within immunodominant HCMV proteins pp65 and IE1 (average score: 98.3). Further, HCMV infection of HFAs mediated a 2‐ to 4‐ fold induction in CXCL10, CD44, and IRGM, reactivity‐associated genes also involved in immune and inflammatory pathways.ConclusionOur data demonstrate that HCMV infection can contribute to AD pathology in cultured astrocytes. These findings could ultimately inform the use of antiviral therapy to prevent and/or reduce AD severity.
Comparison of brain atrophy and cognitive performance in individuals with low and high cardiovascular risk: Data from the Diabetes and Dementia (D2) Study
Authors: Restrepo Carolina , Werden Emilio , Singleton Rebecca , Khlif Mohamed Salah , Bird Laura J. , Ekinci Elif , MacIsaac Richard , Srivastava Piyush , Patel Sheila , Burrell Louise , Brodtmann Amy 
Published: December 2020

AbstractBackgroundGrowing evidence suggests that increased cardiovascular risk might accelerate brain atrophy and cognitive decline. The aim of this analysis was to investigate associations between the Framingham Risk Score (FRS), brain volume and cognitive function in individuals with type 2 diabetes (T2DM) participating in the Diabetes‐and‐Dementia (D2) study.MethodNinety cognitively‐normal participants with T2DM completed neuropsychological assessments, health‐and‐lifestyle questionnaires, 24‐hour ambulatory blood pressure monitoring and a 3T‐MRI scan. FreeSurfer (version 6.0) was used to estimate total brain volume (TBV), mean cortical thickness and subcortical volumes, including the thalami and caudate nuclei. TBV was expressed as a percentage of intracranial volume. Averages between left and right volumes were calculated for subcortical structures. The sample was divided into low (n=45) and high (n=45) FRS groups based on the median score (X=39.7). Differences in volumes were compared between groups. Four cognitive domains, including visuospatial skills, verbal memory, language, and executive functions & speed of processing information, were derived using a factor analysis. These domains were used to compare cognitive performance between individuals with low and high FRS.ResultParticipants in the high FRS group were significantly older and had a lower percentage of women: age (F (1, 89)=26.6; p<0.000); sex (x2=10.07, p=0.01). The high FRS group, after correcting for age and sex, had significantly smaller TBV (F (1, 86)=60.6; p=0.023) and reduced cortical thickness (F (1, 82)=9.93; p=0.002). No difference was found in other subcortical structures. Multivariate analysis revealed a statistically significant difference in cognition between individuals with low and high FRS (F (1, 85)=4.46, p=0.003). Univariate analyses showed statistically significant differences in executive function & processing speed (F (1, 81) = 5.69; p=0.019), with the low FRS group outperforming the high FRS group.ConclusionHigh cardiovascular risk in T2DM is associated with accelerated structural brain aging, manifesting as cerebral atrophy and poorer cognitive function, particularly in processing speed and executive function.
Potential epigenetic pathways linking high mental work demands to dementia risk
Authors: Rodriguez Francisca S. , Leber Markus , Riedel‐Heller Steffi G. , Ramirez Alfredo 
Published: December 2020

AbstractBackgroundMental demands at work are associated with dementia risk. Recent rodent studies with enriched environments suggest that epigenetic alterations moderate such an effect. Aim of the study was to investigate in whether high mental demands at work – as a form of enriched environment – are associated with epigenetic alterations on the GRIN 2B and DNMT 3B and whether this that could explain dementia risk.MethodA case‐control sample (n = 289) was randomly selected from the longitudinal population‐based AgeCoDe study of individuals age 75+. Associations between mental demands at work of the participants’ entire occupational history and methylation of GRIN 2B and DNMT 3B sites and dementia were analyzed using generalized linear regression and logistic regression models adjusted for age, gender, education, depression, diabetes, and smoking.ResultResults suggested associations between the mental work demands ‘Language & Knowledge’ and ‘Information processing’ and the methylation of six GRIN 2B sites and nine DNMT 3B sites. Results indicate that dementia risk is associated with high levels in the mental work demand ‘Language & Knowledge’ together with high methylation of the sites GRIN 2B cg05885720 (OR 0.38, p = 0.011), DNMT 3B cg13681935 (OR 0.26, p = 0.001), DNMT 3B cg13636640 (OR 0.39, p = 0.013), DNMT 3B cg22605822 (OR 0.46, p = 0.049), and a low methylation of DNMT 3B cg09835408 (OR 0.38, p = 0.017). Dementia risk was also associated with high levels in the mental work demand ‘Information Processing’ together with high methylation of the sites GRIN 2B cg05885720 (OR 0.37, p = 0.012), GRIN 2B cg14409083 (OR 0.33, p = 0.006), GRIN 2B cg03777288 (OR 0.39, p = 0.020), DNMT 3B cg22605822 (OR 0.35, p = 0.012), DNMT 3B cg13636640 (OR 0.43, p = 0.029), DNMT 3B cg08240466 (OR 0.39, p = 0.017) and low methylation of DNMT 3B cg09835408 (OR 0.36, p = 0.013).ConclusionIf what the findings suggest is true, then the protective effect of high mental demands at work against dementia is dependent on epigenetic alterations. However, our study is a first attempt to identify potential effect sizes between mental demands at work and DNA methylation on dementia risk long after retirement. Further studies with larger sample sizes need to be designed to gain a better understanding of the underlying associations.
Risk for disorientation: Longitudinal evidence from three old‐age cohorts in Germany (AgeDifferent.de)
Authors: Rodriguez Francisca S , Pabst Alexander , Heser Kathrin , Kleineidam Luca , Hajek Andre , Eisele Marion , Roehr Susanne , Loebner Margrit , Wiese Birgitt , Angermeyer Matthias C. , Maier Wolfgang , Scherer Martin , Wagner Michael , König Hans‐Helmut , Riedel‐Heller Steffi G. 
Published: December 2020

AbstractBackgroundOnly little evidence is available on disorientation, one of the most challenging symptoms of Alzheimer’s disease and related dementias (ADRD). Aim of this study was to investigate the occurrence of disorientation in association with the level of cognitive functioning, personal characteristics, and specific life events.MethodThree population‐based longitudinal cohort studies on cognitive health of elderly adults in Germany were harmonized (AgeDifferent.de platform: LEILA 75+, AgeCoDe/AgeQualiDe, AgeMooDe). Data on cognition, personal characteristics, and life events were collected in standardized interviews and questionnaires with the participant, a proxy informant, and the participant’s general practitioner. Participants who completed the cognitive assessments at follow‐up and who did not have stroke, Parkinson’s, atherosclerosis, kidney infection/disease, and/or alcoholism were included in the analysis (n=2135).ResultOlder age, a lower MMSE score (without the disorientation items), impairments in walking and being divorced or widowed came with a greater likelihood of having disorientation. Incident disorientation over the study period was predicted by older age, a lower MMSE score (without the disorientation items) and living in a nursing home. Of the life events that we investigated, only the event ‘moving’ was significantly associated with a greater likelihood of incident disorientation. Subgroub analyses for dementia patients emphasize the relevance of certain cognitive deficits.ConclusionClinicians and health care workers should be aware that elderly people with decreased cognitive functioning who have difficulties walking, disrupted family relationships, and are in the process of moving to a new home are more likely to experience disorientation. More research is needed to identify specific situations that trigger disorientation at certain stages of dementia.
‘No, I don't know where that is. All I know is my room.’: Topographical disorientation and user‐centred requirements for in‐hospital navigation aids of people with dementia and their caregivers
Authors: Kowe Antonia , Goerss Doreen , Teipel Stefan J. 
Published: December 2020

AbstractBackgroundHospitals are complex buildings in which the risk of disorientation is high with negative consequences on financial and staff resources due to missed appointments and increased need of support. Existing indoor navigation aids, such as accompanying services, spatial design or technical assistance, often miss the intended users’ needs. Based on the value sensitive design approach, this study asked people with dementia (PwD) and their caregivers about the requirements in‐hospital navigation aids should fulfil for them to be considered useful.MethodWe conducted semi‐structured interviews with two stakeholder groups of stationary dementia care: PwD (n = 10, agemean = 83,9 years) and informal caregivers (n = 5, agemean = 73,8 years). In the interviews, we asked for previous experiences including barriers for the use of existing navigation aids. We analysed underlying values and requirements for improved technologies. The interviews were evaluated using qualitative content analysis according to Mayring.ResultAccompanying services by hospital staff or relatives were considered by respondents to be the most helpful support for in‐hospital orientation. Barriers for the use of existing in‐hospital navigation aids are their low visibility and lacking need of usage due to restricted mobility of in‐patients with dementia. Interestingly, some PwD are willing to use technical assistance for navigation support although their digital competencies are considered to be very low by caregivers. For both stakeholder groups, trust is an important value in technical devices for navigation. PwD highlighted independence as further important value while caregivers prioritized safety. Both respondents groups wanted a device that could be worn on the body and that gave simple instructions for finding rooms via visual or acoustic signals.ConclusionPwD and caregivers can specify needs for in‐hospital navigation aids and their requirements differ only slightly due to varying values. User‐centred design potentially helps to improve emerging technologies for patient‐centred stationary care.
Alzheimer's disease phenotypes misdiagnosed with frontotemporal lobar degeneration: A retrospective neuropathologic study
Authors: Lecerf Simon , Leroy Melanie , Lebouvier Thibaud , Lebert Florence , Deramecourt Vincent , Maurage Claude Alain , Pasquier Florence 
Published: December 2020

AbstractBackgroundAlzheimer's disease (AD) is a heterogeneous illness, with a common clinical presentation of progressive amnesia and less common « atypical » presentations which may be misdiagnosed with a pathology of the frontotemporal lobar degeneration (FTLD) spectrum. This study sought to characterize which phenotypes of AD are difficult to distinguish from FTLD.MethodAmong the patients followed in the Lille Memory Clinic (France) between 1993 and 2018 and having a neuropathologic diagnosis of AD, the clinical phenotypes of those for whom there was a diagnostic hesitation between AD and FTLD (« doubt group », n = 13) were compared with the clinical phenotypes of those for whom there was no hesitation in diagnosing AD (« no doubt group », n = 40).ResultA primary progressive aphasia (PPA) phenotype and a corticobasal syndrome (CBS) phenotype are most likely to be found in the « doubt group » (PPA n = 8/13, 62,5% ; CBS n = 2/13, 15,4%) than in the « no doubt group » (PPA n = 1/40, 2,5% ; CBS n = 0/40, 0%). In this study, no patient with confirmed AD fulfilled precociously the Rascovsky criteria for possible behavioural variant of frontotemporal dementia (bvFTD).ConclusionAs reported, PPA and CBS phenotypes are syndromes that can be observed in AD as in FTLD. Frontal variant of AD seems very uncommon.
EEG: A valuable tool to screen for neurodegeneration in preclinical Alzheimer’s disease
Authors: Gaubert Sinead , Raimondo Federico , Houot Marion , Corsi Marie‐Constance , Naccache Lionel , Sitt Jacobo Diego , Hermann Bertrand , Oudiette Delphine , Gagliardi Geoffroy Pierre , Habert Marie‐Odile , Dubois Bruno , Fallani Fabrizio De Vico , Bakardjian Hovagim , Epelbaum Stéphane ,   the Alzheimer’s Disease Neuroimaging Initiative, the MEMENTO study group and the INSIGHT‐preAD study group
Published: December 2020

AbstractBackgroundEarly biomarkers are needed to identify individuals at high risk of preclinical Alzheimer’s disease (AD) (Jack et al., 2018). Electroencephalography (EEG) is a non‐invasive and cheap technique that would be an interesting screening tool for the preclinical stage of AD.MethodWe included participants from the INSIGHT‐preAD cohort, which is an ongoing single‐center multimodal observational study designed to identify risk factors and markers of progression to clinical AD in 318 cognitively normal individuals aged 70–85 years with a subjective memory complaint (Dubois et al., 2018). We divided the subjects into four groups, according to their amyloid status (on 18F‐florbetapir PET) and neurodegeneration status (on ¹⁸F‐fluorodeoxyglucose PET). We analysed 314 baseline 256‐channel high‐density eyes‐closed 1‐minute resting‐state EEG recordings. We extracted 10 quantitative EEG biomarkers, including spectral measures, algorithmic complexity and functional connectivity metrics. We evaluated three different classifiers (random forest, decision tree and logistic regression) to predict amyloid and neurodegeneration status from multimodal data, combining EEG, ApoE4 genotype, demographic, neuropsychological and MRI data. We divided the dataset into a training set (n=258) and validation set (n=46). We used a 5‐fold cross‐validation on the training set to identify the optimal combination of features.ResultAs recently published (Gaubert et al., 2019), the most prominent effects of neurodegeneration on EEG metrics were localized in fronto‐central regions with an increase in high‐frequency oscillations (higher beta and gamma power) and a decrease in low‐frequency oscillations (lower delta power), higher spectral entropy, higher complexity and increased functional connectivity measured by weighted Symbolic Mutual Information in theta band. In the machine learning analysis, among the different features, EEG was the most strongly predictive of neurodegeneration. Similar predictive performance was obtained when reducing the number of electrodes from 256 to 8. EEG biomarkers combined with hippocampal volumetry had a high negative predictive value (91%) and high sensitivity (82%) to predict neurodegeneration. The combination of ApoE4 genotype with demographic data was most strongly predictive of amyloid status.ConclusionEEG could be a valuable tool to screen for or rule out neurodegeneration in elderly memory complainers. This procedure has been patented under the following PCT number: PCT/EP2019/086629.
Interaction of neuropsychiatric symptoms with APOE e4 and conversion to dementia in MCI patients in a memory clinic
Authors: Valero Sergi , Marquie Marta , Rojas Itziar , Moreno Sonia , Espinosa Ana , Orellana Adelina , Montrreal Laura , Hernandez Isabel , Mauleon Ana , Rosende‐Roca Maitee , Alegret Montserrat , Pérez‐Cordón Alba , Ortega Gemma , Roberto Natalia , Sanabria Angela , Abdelnour Carla , Gil Silvia , Tartari Juan Pablo , Vargas Liliana , Antonio Ester Esteban‐De , Benaque Alba , Tarraga Lluis , Boada Mercè , Ruiz Agustín 
Published: December 2020

AbstractBackgroundTo the date, scarce studies have been focused in the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE e4 on conversion to dementia in Mild Cognitive Impaired patients (MCI). None of them taking into account clinical settings of MCI patients. The objective was to determine the predictive value of additive and multiplicative interactions of NPS and APOE e4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic.Method1512 patients (aged 60 and older) with prevalent MCI have been followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated, and several clinical variables were used as an adjusting factors, including the memory impairment condition, the attributed etiological pattern, and the antidepressant and anxiolytic medication used.ResultAdditive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, increasing significantly the hazard ratios of incident dementia (HR range 1.3 – 2.03).ConclusionSynergistic interactions between NPS and APOE e4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.