bluuebunny/crossref_metadata_2025_split huggingface dataset:
ApoE4 binding in dried blood spots is associated with lower cognition in a population‐based sample of 50+ non‐demented adults
Authors: Araujo Yacila I. Deza , Weiss Luzia M , Groh Rebecca , Horton Hannah M. , Borbye‐Lorenzen Nis , Skogstrand Kristin , Holmgaard Solveig , Andersen‐Ranberg Karen , Ludmark Vania Panes , Börsch‐Supan Axel , Börsch‐Supan Martina , Rieckmann Anna 
Published: June 2023

AbstractBackgroundThe ApoE ε4 allele is a major risk factor for late‐onset Alzheimer’s disease and cognitive decline in ageing (Corder et al., 1993) but the role of the circulating ApoE4 protein on cognition is still under debate (Simon et al., 2012; Wang et al., 2014). Here, we report the distribution of circulating ApoE4 protein, assessed from dried blood spots, in a large population‐based sample. Preliminary analyses examined its associations with cognition and lifestyle factors.MethodMeasures of memory (word recall), verbal fluency and dried blood spot samples were collected during the 6th Wave of the Survey of Health, Ageing and Retirement in Europe ‐ SHARE (N = 12,531, 50y and over, 59.3% females). An assay to specifically bind to the ApoE4 protein in dried blood spots was developed. Data driven cut‐offs were tested to divide the ApoE4 binding distributions in specific and non‐specific types. Next, multiple linear regressions were used to test the association between ApoE4 binding type and cognition. Models were adjusted for available demographic, lifestyle and health‐related variables. Interaction terms between age and ApoE4 binding type were created. Finally, specific binding levels were used as a continuous outcome to assess whether they were associated with demographic, health or lifestyle variables.ResultA cut‐off of 50.000 pg/mL was chosen to separate the distributions of specific (28.4%) vs. non‐specific (71.6%) ApoE4 binding (Fig. 1). Belonging to the specific binding group had a significant negative effect on word recall (ps < 0.001) but not on verbal fluency. Interaction effects between age and specific ApoE4 binding were observed in all models, with the effect of specific ApoE4 binding on cognition magnified for adults aged 75‐84y (Fig. 2A, 2B and 2C). Finally, higher BMI, female sex and hypertension (all ps < 0.05) were predictors of higher levels of specific ApoE4 binding.ConclusionSpecific and non‐specific binding to the ApoE4 protein, assessed in dried blood spots, followed known population frequencies of ApoE ε4 allele (Gerdes, 2003). Specific ApoE4 binding was associated with worse cognitive performance. Higher specific ApoE4 levels were associated with female sex and cardiovascular factors.
Accelerated long‐term forgetting‐ALF in Mild Cognitive Impairment: A sensitive tool for subtil memory problems
Authors: Berrios Waleska , Campora Nuria , Fernandez Maria Cecilia , Genero Agustina , Rugiero Marcelo , Golimstok Angel 
Published: June 2023

AbstractBackgroundAccelerated long‐term forgetting (ALF) has been considered a memory consolidation problem, whereby a person can learn and recall information accurately for a limited period of time, but then exhibits a long delayed recall deficit. Standard episodic memory tests which assess long delayed recall consider a delay interval up to 40 minutes after the initial learning. ALF could not be detected by this method. The aim of this study was examining ALF phenomenon in a population of Mild Cognitive Impairment (MCI) patients and normal cognitive performance (NC) individuals.MethodPatients with cognitive complaints were included during a period of 1 year, according to selection criteria. A standard neuropsychological test battery was administered. In order to assess ALF we used the Logical Memory (LM) subtest of Signoret’s memory battery. We registered immediate recall, delayed recall at 30‐minutes and long delayed recall at 7‐days. We also proposed that the performance of long delayed recall at 7‐days ≤50% of the value of delayed recall at 30‐minutes in LM could be considered ALF.ResultDuring a 1 year‐period 115 patients were included, as “G1” 84 MCI patients and “G2” 31 NC individuals. Demographics data: 1) G1 mean age was 73.06±9.99 years, mean education was 12.17±4.28 years and 39(46.42%) were females; 2) G2 mean age was 67.03±8.28 years, mean education was 14.4±3.8 years and 24(77.41%) were females. The performance in memory tests showed that G1 had lower values in long delayed recall at 7‐days compared to G2 with statistical significance (G1 3.65±2.59 vs G2 6.16±2.6; p = 0.001). When we applied our proposal for ALF, just 7(22.6%) patients of G1 and 26(31%) of G2 had a performance of long delayed recall at 7‐days ≤50% of the value of delayed recall at 30‐minutes in LM without statistical difference (p = 0.378).ConclusionUntil the date, there isn’t an agreement in memory test to use or delay interval to consider or normative data available to detect ALF. While our proposal doesn’t differentiate between MCI and NC patients, it is necessary to continue studies and produce normative data.
Assessing biomarkers of awareness in people with advanced Alzheimer’s disease in care homes‐ a feasibility and pilot study
Authors: Huntley Jonathan D 
Published: June 2023

AbstractBackgroundThere is an urgent need to understand the nature of awareness in advanced AD to ensure effective person‐centred care. As dementia progresses, it can become very difficult for family members and caregivers to understand the lived experience of a person with advanced dementia, and assumptions are often made about their level of awareness and quality of life based on observations of behaviour. However, such observations are subject to bias and misinterpretation. In addition, there are anecdotal reports of variability of awareness with apparent moments of lucidity, however there is no objective data on how this relates to changes in underlying brain activity or subjective experience.MethodThis feasibility and pilot study uses of electrophysiological and physiological biomarkers to assess awareness and emotional responsiveness in a real‐world setting. These approaches include 1) 7 channel EEG 2) Bispectral index monitoring 3) physiological markers of emotional response (heart rate, electrodermal activity, accelerometry, temperature). These data were collected during a 1 hour protocol involving rest, musical stimulation, visual stimulation and interaction with caregivers.ResultWe report the feasibility of using these approaches in 15 people with advanced dementia (sMMSE 0, CDR 3) who reside in specialist dementia care homes. Data was collected in the ‘real world’ care home setting and was feasible and acceptable to people with advanced dementia, family members and care home staff. Preliminary data will be presented on baseline biomarkers of awareness and arousal in advanced AD, and whether EEG and physiological markers can differentiate between rest and emotionally salient conditions.ConclusionThese biomarkers provide experimental approaches to assess awareness and improve understanding and care for people with advanced AD.
Involvement of striatal motoric subregions in familial frontotemporal dementia with parkinsonism harboring the C9orf72 repeat expansions
Authors: Liu Li , Liu Shuying , Chu Min , Xie Kexin , Cui Yue , Rosa‐Neto Pedro , Wu Liyong 
Published: June 2023

AbstractBackgroundThe chromosome 9 open reading frame 72 (C9ORF72) has been proposed as the causative gene of frontotemporal dementia with parkinsonism (FTDP), but its pathophysiological mechanism of parkinsonism is poorly understood.MethodTo explore the roles of striatal motor subdivisions in the pathogenesis of parkinsonism resulting from C9ORF72 repeat expansions in the FTDP, two patients with FTDP from one pedigree and seventeen healthy controls were enrolled. The participants received clinical interviews and underwent neuropsychological assessments, genetic testing, [18F]‐fluorodeoxyglucose PET/MRI, and [18F]‐dihydrotetrabenazine PET/CT. Voxel‐wise and region of interest analysis were conducted with respect to gray matter volume, metabolism, and dopamine transport function between patients and controls, focusing on the motor part of the striatum according to the Oxford‐GSK‐Imanova Striatal Connectivity Atlas.ResultPatient 1 presented with parkinsonism as the initial symptom, while patient 2 exhibited behavior disturbance as the first symptom, followed by parkinsonism within one year. Both patients had the hexanucleotide expansion detected in C9ORF72(>52 repeats). Gray matter volume atrophy, hypometabolism and dopamine dysfunction were observed in the motor areas of the striatum. Of the two patients, marked glucose hypometabolism within the striatal motor subregion was observed in patient 1, with corresponding gray matter atrophy. In addition, presynaptic dopaminergic integrity of patient 2 was deteriorated in the motor subregions which was consistent with gray matter atrophy.ConclusionThese findings provide evidence that C9orf72 repeat expansions could result in degeneration and dopaminergic dysfunction of the striatal motor subregion, which contributed to parkinsonism in FTDP.
Circulating extracellular vesicles of neurovascular origin are elevated in women with severe preeclampsia years after their affected pregnancies
Authors: Suvakov Sonja , Norby Alexander , Abou‐Hassan Coline , Milic Natasa , Rajovic Nina , Jayachandran Muthuvel , Kantarci Kejal , Mielke Michelle M. , Garovic Vesna D 
Published: June 2023

AbstractBackgroundPreeclampsia (PE), a pregnancy specific hypertensive disorder, has been associated with elevated risk for strokes, cognitive decline, and smaller brain volumes later in life. As severe PE has been associated with the highest risks for cerebrovascular disease, we hypothesized that circulating extracellular vesicles (EVs) of neurovascular origin will be detectable in women years after severe PE as a marker of persistent neurovascular damage and amyloid‐β.MethodA cohort of 40 women with histories of normotensive pregnancies (control group) and age‐ and parity‐matched to 40 women with history of mild (n = 33) and severe (n = 7) PE were identified using the Rochester Epidemiology Project. Diagnosis of severe PE was ascertained based on clinical criteria (Table). While none of the women had any major cardiovascular events, our previous study of this cohort has demonstrated that total gray matter volumes were smaller in women with a history of preeclampsia and late‐life hypertension compared with the other groups. Blood‐borne EVs derived from neurovascular cellular activation were determined by standardized digital flow cytometry. Plasma concentration of amyloid‐β was measured by ELISA. Differences among the groups were tested by ANOVA, with the least difference test for pos hoc analysis. The association between EVs and MRI brain imaging was assessed by Pearson correlation coefficient.ResultWomen with history of severe PE had a significantly higher concentration of amyloid‐β carrying EVs compared to controls (p = 0.003). EVs positive for the markers of blood‐brain barrier‐ endothelial damage (LDL‐R) and inflammatory coagulation pathway activator (tissue factor), were significantly higher in women with history of severe PE compared to controls (p = 0.008 and p = 0.002, respectively), as well as to the women with history of mild PE. Plasma concentration of total amyloid‐β was also significantly greater in women with history of severe vs. mild PE (p = 0.037) (Table). The number of tissue factor positive EVs was negatively correlated with total gray matter volume (cm3) (p<0.05).ConclusionWomen with a history of severe PE demonstrate elevated levels of markers of neuroinflammation and neurovascular damage, as well as greater amyloid‐β secretion. Excessive inflammation may contribute to previously described brain atrophy in these women.
Semantic variant Primary Progressive Aphasia: Additional semantic features in Chinese language users
Authors: Tee Boon Lead , Chen Lorinda Li‐Ying Kwan , Chen Ta‐Fu , Wang Pei‐Ning , Lu Chien Jung , Chan Andrew LT , Gorno‐Tempini Marilu 
Published: June 2023

AbstractBackgroundTo date, most literature on Primary Progressive Aphasia (PPA) has been based on English language users. Yet, there are more than 7,000 living languages worldwide with vast heterogeneities in their linguistic features. Contrary to English language, Chinese language is a classifier language in which it is grammatically mandatory to have classifiers present between numerals and nouns. In addition, Chinese characters typically have an abundance of homophones (i.e., words with same pronunciation but vary in orthography and meaning) and heteronyms (i.e., words with same orthography but vary in meaning and pronunciation). Chinese language users rely on semantic knowledge to identify the accurate classifiers, homophones, and heteronym pronunciations. Thus, we hypothesize that Chinese‐speaking semantic variant (sv) PPA patients have difficulties producing classifiers, homophones, and heteronyms.MethodTo assess classifier production, participants are presented with pictures of nouns. Participants are first tasked with producing noun‐specific classifiers spontaneously. If failed, they are presented with four classifiers to select. To evaluate homophone selection skills, participants are shown short sentences with one character/word removed. They are then tasked to complete the sentences by choosing one of the four homophones presented. For heteronym reading, participants are asked to read out loud Chinese compound words with heteronyms (e.g., “windmill” and “wind up”).ResultWe recruited 22 controls and 47 PPA individuals (12 svPPA, 10 nonfluent variant (nfv) PPA and 25 logopenic variant (lv) PPA). In classifier production test, svPPA and lvPPA patients produce fewer accurate classifiers (p<0.0001, p = 0.001), with svPPA showing least improvement when presented with multiple choices (p = 0.003). In homophone selection test, svPPA and lvPPA scored lower than controls (p<0.0001 and p = 0.007). For heteronym reading test, svPPA showed the lowest performance when tasked with reading heteronym characters (p = 0.001). Using voxel‐based morphometry, we noted that the ability to produce classifiers, read heteronyms and identify heteronyms are correlated with grey matter volumetric changes over the anterior portion of the left temporal lobe and fusiform gyri, brain regions associated with language semantic functions.ConclusionPPA symptomatology may vary across languages. Thus, studying PPA symptoms via a linguistically diverse approach potentially provides a more comprehensive understanding to the syndrome.
Cerebral amyloid‐β deposition in patients with diseases of the heart or carotid arteries: A systematic review and meta‐analysis
Authors: Starmans Naomi LP , Leeuwis Anna E , Biessels Geert Jan , Kappelle Jaap , van der Flier Wiesje M. , Tolboom Nelleke 
Published: June 2023

AbstractBackgroundCardiovascular disease is increasingly recognized as a contributor to cognitive impairment. Reduced cerebral blood flow alone does not explain this association. Another contributing mechanism could be increased cerebral amyloid‐β accumulation. We hypothesized that patients with diseases of the heart or carotid arteries have more cerebral amyloid‐β accumulation than patients without these diseases.MethodWe conducted a systematic review to determine whether there is an association between diseases of the heart (heart failure, myocardial infarction, heart valve diseases, arrhythmias and cardiomyopathies) or carotid arteries (stenosis or occlusion of the extracranial internal carotid arteries (ICA)) and cerebral amyloid‐β accumulation, measured with positron emission tomography. We searched Pubmed, EMBASE and Scopus for studies that matched inclusion and exclusion criteria. Where possible, we obtained standardized mean differences (SMD) of amyloid‐β standardized uptake volume ratios (SUVr) with a meta‐analysis using a random‐effects model.ResultSeven cross‐sectional studies, two on heart diseases and five on carotid artery diseases, were identified, including a total of 1262 participants (mean age 60‐76 years, 53% female). Six of the seven studies did not find a difference in cerebral amyloid‐β accumulation between patients with or without heart or carotid artery disease. One study including 11 participants found more amyloid‐β in the hemisphere ipsilateral to an ICA stenosis than in the hemisphere of healthy controls. SMD were calculated for atrial fibrillation (AF) (two studies including 746 participants) and unilateral ICA stenosis or occlusion (two studies including 24 participants). Patients with AF tended to have more cerebral amyloid‐β than reference participants (SMD in SUVr 0.14, 95% CI ‐0.06 – 0.34). There was less amyloid‐β in the hemisphere ipsilateral to the ICA stenosis or occlusion compared to the contralateral hemisphere (SMD in SUVr ‐0.13, 95% CI ‐0.70 – 0.43). Although we did not find significant effects.ConclusionCurrently available evidence does not support the notion that diseases of the heart or carotid arteries predispose for a higher burden of cerebral amyloid‐β.
Subtle cognitive impairment is associated with subtle instrumental activities of daily living defecits, but not severity of memory complaints in sucjective cognitive decline
Authors: Ryu Seon Young , Lee Sang Bong , Lee Taek Jun , Jung Yu Jin 
Published: June 2023

AbstractBackgroundSubjective cognitive decline (SCD) can be considered as the preclinical manifestation of Alzheimer’s disease. The objective of this study was to examine whether there would be differences of the clinical correlates due to evidence of subtle cognitive imparment (SCI) in inividuals with SCD.MethodOne‐hundred‐and‐fifty‐five individuals with SCD (mean age: 68.18 ± 8.09 years) were included in this study. The participants underwent clinical assessments and completed detailed neuropsychological tests. The functional assessment was performed by the Korean Instrumental Activities of Daily Living (IADL) scale. Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ) consisting of 16 items that describe everyday memory failure.ResultSCD individuals with SCI (n = 20) had lower Mini‐Mental State Examination scores and showed lower performances in the neuropsychological tests than the SCD only group (n = 135). In addition, the SCI group had worse IADL performance than the SCD only group. There were no differenes in depressive symptoms and PRMQ scores between two groups.ConclusionIn SCD individuals, SCI was associated with subtle IADL deficits, but not with the severity of self‐reported memory complaints, compared to the SCD only group. These results suggest that functional assesments would be helpful for the clinical evaluation of individuals with SCD.
Characterization of altered neuroenergetic patterns in Alzheimer’s Disease using combined FDG‐PET and sodium MRI
Authors: Haeger Alexa , Fuchs Annalena , Romanzetti Sandro , Bottlaender Michel , Boumezbeur Fawzi , Lagarde Julien , Rabrait‐Lerman Cécile , Holtbernd Florian , Sarazin Marie , Winz Oliver , Heinzel Alexander , Mottaghy Felix M. , Schulz Jörg B. , Reetz Kathrin 
Published: June 2023

AbstractBackground[18F]‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) positron emission tomography (PET) is applied to delineate cerebral glucose metabolic patterns in Alzheimer’s disease (AD). Sodium MR imaging (23Na‐MRI) can reveal alterations in tissue sodium concentration (TSC) in the brain, potentially reflecting mitochondrial dysfunction and impaired cellular energy state. This initial study aims at investigating disease‐specific topographical associations between glucose metabolism assessed via FDG‐PET and regional TSC from 23Na‐MRI, thus improving our understanding of neuroenergetics alteration in AD.Method20 patients with a biological biomarker‐based diagnosis of prodromal/mild AD (mean age 68±7.5; 8 females; CDR 0.75±0.57, MMSE 23.9±4.2) received an FDG‐PET, 23Na‐MRI and 1H‐MRI at 3T magnetic field (Siemens Prisma). A variable flip angle method was used to obtain TSC maps (Coste et al., 2019). To control for inter‐individual differences, FDG‐PET and TSC images were intensity‐normalized to the brainstem to create normalized glucose metabolism (nFDG) and normalized TSC maps (nTSC) (de Souza et al., 2011; Nugent et al., 2020), respectively. The Hammersmith and VolBrain Segmentation atlases were applied for region‐of‐interest analysis and to create correlation matrices between nFDG, nTSC and normalized local brain volume.ResultRegional nTSC negatively correlated with nFDG in AD patients mainly in temporal lobe structures and superior frontal gyri, indicating that decreased glucose metabolism was associated with increased TSC and vice versa. As expected, regional volume was positively correlated with nFDG in regions of the temporal lobe. When performing partial correlation controlling for volume, negative correlation clusters between nTSC and nFDG remained significant for superior frontal gyri and the anterior temporal lobes (Figure 1).ConclusionFor the first time, the association between local glucose consumption rates and sodium concentrations were investigated in AD using combined FDG‐PET and 23Na‐MRI at 3T. Consistently to our recent findings of increased TSC in AD patients (Haeger et al., 2021), the negative correlations between nTSC and nFDG values in temporal and frontal brain regions, are confirming the interplay between reduced energy metabolism and sodium increase in AD, the exact nature of which remains to be determined.References: Coste […]. Magnetic Resonance Imaging 2019.Haeger […]. Alzheimer’s & Dementia 2021.Nugent […]. Scientific Reports 2020.de Souza […]. Brain 2011.