bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo brainstem tau pathology is related to entorhinal amyloid pathology in middle‐aged healthy participants
Authors: Meyer François , Justinas Narbutas , Van Egroo Maxime , Dapnée Chylinski , Bahri Mohamed Ali , Ekaterina Koshmanova , Besson Gabriel , Vincenzo Muto , Christina Schmidt , Luxen André , Phillips Christophe , Pierre Maquet , Gilles Vandewalle , Collette Fabienne , Bastin Christine , Salmon Eric 
Published: June 2023

AbstractBackgroundBraak’s model of Alzheimer’s disease (AD) progression suggests that the initial accumulation of hyperphosphorylated tau protein is seen in the locus coeruleus (LC). Tau pathology might be a good marker of subsequent cognitive decline in initially unimpaired participants. We capitalized on Braak’s model to assess in a sample of cognitively unimpaired late‐middle‐aged individuals, the relationship between tau and Aß accumulation in the locus cœruleus, basal forebrain (BF) and entorhinal cortex (ERC).Method65 participants aged 50‐70 years were enrolled in a multimodal cross‐sectional study investigating the relationship between AD neuropathology, cognitive aging and cognitive complaints, and life style.MRI acquisitions were performed on a 3‐T scanner (MAGNETOM Prisma, Siemens). Tau and Aß‐PET were performed on an ECAT EXACT+ HR scanner (Siemens). [18F]THK5351‐PET was used as a proxy of tau accumulation and Aß‐PET radiotracer was [18F]Flutemetamol.Masks were used for entorhinal cortex (ERC), basal forebrain (BF) and locus cœruleus (LC). We extracted Tau and Aß burden in each region of interest, for a total of ten neuroimaging AD biomarkers (LC‐Tau, LC‐Aß, BF123‐Tau, BF123‐Aß, BF4‐Tau, BF4‐Aß, right and left ERC‐Tau, right and left ERC‐Aß).Statistical analyses. All statistical analyses were performed with SAS 9.4 for Windows (SAS Institute, Cary, NC, USA) using the GLIMIX model.ResultWe found direct correlations between LC‐tau and left ERC‐Aß (F = 6.86, p = .0112) or LC‐tau and right ERC‐Aß (F = 14.12, p = .0004), and also between LC‐Tau and BF4‐Aß. However, a model including the interactions between LC‐Tau, BF4‐Aß and ERC‐Aß, was not significant. Stepwise analysis confirmed a significant liability of the model to explain ERC‐Aß (F = 5.86, p = .0048 for left and F = 6.83, p = .0005 for right ERC, for which LC‐tau had the main contribution (F = 14.12, p = .0004).ConclusionOur results showed a positive and significant correlation between Tau burden in the LC and amyloid burden in the ERC. The relationship between these two AD biomarkers was observed in healthy individuals without any cognitive impairment.
Undiagnosed Alzheimer’s disease and related dementias among foreign‐born Middle Eastern and North African adults in the United States
Authors: Kindratt Tiffany B , Dallo Florence J , Zahodne Laura B. , Ajrouch Kristine J 
Published: June 2023

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) disparities exist by race/ethnicity and nativity (Mehta & Yeo, 2017). Non‐Hispanic blacks and Hispanics are more likely to have ADRD and to be undiagnosed than non‐Hispanic whites (Amjad et al., 2018; Gianattasio et al., 2019). The prevalence of undiagnosed ADRD among Middle Eastern and North African (MENA) adults in the US remains unknown. MENA men tend to report better health than women regardless of immigrant status (Read & Reynolds, 2012). Our aims were to: 1) estimate and compare estimates of suspected undiagnosed ADRD among foreign‐born MENA adults compared to US‐ and foreign‐born non‐Hispanic whites and 2) compare estimates stratified by sex.MethodWe linked data from the 2000‐2017 National Health Interview Survey and 2001‐2018 Medical Expenditure Panel Survey (ages > = 65 years, n = 23,981). ICD‐9 (290/294/331/797) and ICD‐10 (F03/G30) codes were used to measure ADRD diagnosis. Undiagnosed ADRD was suspected if a participant reported having a cognitive limitation without a corresponding ADRD diagnosis. Bivariate and multivariable logistic regression analyses adjusted for age, sex, and potentially modifiable risk factors (education, hearing loss, hypertension, depression, social isolation, and diabetes) were conducted.ResultThe prevalence of suspected undiagnosed ADRD was highest among foreign‐born MENA adults (15.8%) compared to US‐ (8.1%) and foreign‐born (11.8%) non‐Hispanic whites. The age‐adjusted and sex‐stratified prevalence of suspected undiagnosed ADRD was higher among MENA women (22.5%) than MENA men (9.3%) and lowest among US‐born white men (7.6%). In fully adjusted logistic regression models, foreign‐born MENA adults had 1.98 times greater odds (95% CI = 1.09‐3.60) of undiagnosed ADRD compared to US‐born non‐Hispanic whites. There were no differences between foreign‐born MENA men and US‐born non‐Hispanic white men. Foreign‐born MENA women had 2.89 times greater odds (95% CI = 1.49‐5.60) of undiagnosed ADRD compared to US‐born white women.ConclusionThis study contributes the first national estimates of suspected undiagnosed ADRD among MENA men and women. Furthermore, our study highlights that the underdiagnosis of ADRD among MENA adults may be driven by women. Results will help to facilitate policy decisions and advocate for resources to be allocated for interventions to improve the health of this underrepresented but increasingly visible minority population.
Association between the estimated 10‐year cardiovascular mortality risk and cognitive function in older adults: results from the FINGER trial
Authors: Stephen Ruth , Hall Anette , Lehtisalo Jenni , Ngandu Tiia , Laatikainen Tiina , Rusanen Minna , Strandberg Timo , Antikainen Riitta , Tuomilehto Jaakko , Lindstrom Jaana , Peltonen Markku , Hänninen Tuomo , Soininen Hilkka , Kivipelto Miia , Barbera Mariagnese , Solomon Alina 
Published: June 2023

AbstractBackgroundDementia risk scores could be instrumental in the implementation of multidomain lifestyle interventions for dementia prevention. However, as relatively new tools, their performance requires further validation. Given the extensive overlap between risk factors for dementia and cardiovascular disease (CVD), multidomain interventions usually have an important vascular component and better‐established cardiovascular risk scores could become useful in this context. More evidence is needed on their ability to predict the risk of cognitive decline and dementia. SCORE/SCORE‐Older People (OP) are the official tools of the European Society of Cardiology to estimate the 10‐year CVD‐mortality risk. In this study, we investigated the association between SCORE/SCORE‐OP and cognitive function within FINGER, the first large trial showing the efficacy of a multidomain lifestyle‐ and vascular‐based intervention in preventing cognitive decline.MethodSCORE (age<65) and SCORE‐OP (age≥65) were calculated in the population of the 2‐year FINGER trial (N = 1236, baseline and 24 months). The cognitive outcomes (baseline, 12 and 24 months) were the overall z‐score from a Neuropsychological Test Battery (NTB, 14 tests, primary outcome) and the z‐scores of the NTB cognitive domains (Memory, Executive Function, and Processing Speed, secondary outcomes). The associations between (i) SCORE/SCORE‐OP and cognition, (ii) SCORE/SCORE‐OP and changes in cognition, and (iii) changes SCORE‐OP and changes in cognition were assessed using linear mixed‐models repeated‐measures with maximum likelihood estimation.ResultHigher baseline risk of CVD‐mortality, estimated with SCORE/SCORE‐OP, was significantly and consistently associated with worse cognition, (NTB total composite: Estimate = ‐0.036; CI: ‐0.042 to ‐0.030; P‐value>0.0001; individual NTB cognitive domains: P‐values<0.0001) and yearly lower improvement in cognitive performance (NTB total composite: Estimate = ‐0.009, CI: ‐0.011 to ‐0.007, P‐value>0.0001; individual NTB cognitive domains: P‐values<0.0001). 2‐year change in SCORE‐OP was not significantly associated with changes in cognition during the FINGER study period.ConclusionSCORE/SCORE‐OP could be useful in predicting the risk of cognitive decline in a trial aimed at improving lifestyle and vascular‐related risk factors of dementia. However, more evidence is needed on their efficacy in predicting dementia risk and the response to multidomain lifestyle‐ and vascular‐ based interventions. Future studies on other well‐established and easy‐access cardiovascular risk scores could also provide relevant findings.
The novel visual cognitive assessment test correlates well with plasma oligomeric amyloid beta in patients with mild cognitive impairment
Authors: Sandhu Gurveen Kaur , Zailan Fatin Zahra , Vipin Ashwati , Soo See Ann , Kumar Dilip , Ng Kok Pin , Kandiah Nagaendran 
Published: June 2023

AbstractBackgroundOligomeric Amyloid Beta (OAβ), is representative of a soluble, neurotoxic and pathogenic form of Aβ, which has been found to function as upstream drivers of Alzheimer’s Disease pathology (Tolar et al., 2021). It serves as a contributory factor towards the formation of cortical Aβ plaques and neurofibrillary Tau tangles, and has been found to induce oxidative stress, synaptic toxicity and neuroinflammation (Tolar et al., 2021). The pathology culminates in neuronal dysfunction/death and resultant neurodegeneration which has been found to manifest clinically as symptoms of cognitive decline. OAβ has been found to correlate with the severity of cognitive performance, as well as brain volume reduction (An et al., 2017, Wang et al., 2017, Meng et al., 2019, Youn et al., 2019, Babapour Mofrad et al., 2021). Nevertheless, its effect on language neutral cognitive tests ‐ the novel Visual Cognitive Assessment Test (VCAT) developed and validated by our team of neurologist and neuropsychologists; remains to be evaluated (Kandiah et al., 2016, Lim et al., 2018, Low et al., 2020).MethodsA cross‐sectional pilot study was conducted in a cohort of 63 patients, clinically diagnosed with mild cognitive impairment (MCI). The patients underwent cognitive evaluation tests, Multimer Detection System (MDS) based plasma OAβ analysis and MRI based cortical grey matter evaluations (Wang et al., 2017, Youn et al., 2019, Pyun et al., 2021, Vipin et al., 2021). Pearson’s correlation evaluated associations between plasma OAβ, cognitive scores [Mini‐Mental State Examination (MMSE), VCAT] and brain volume measures [Grey Matter Volume (GMV) / Intracranial Volume (ICV)].ResultsIncreasing plasma OAβ expression associated with decreasing, VCAT scores (r = ‐0.291, 95% CI = ‐0.504 to ‐0.044, p = 0.022) and MMSE scores (r = ‐0.272, 95% CI = ‐0.489 to ‐0.024, p = 0.032), in MCI patients (Figure 1A, B). Additionally increasing plasma OAβ expression also associated with decreasing and GMV/ ICV ratio (r = ‐0.264, 95% CI = ‐0.489 to ‐0.007, p = 0.045), in MCI patients (Figure 1C).ConclusionFindings from this study, emphasise on the promising clinical utility of plasma OAβ as a biomarker. Future longitudinal studies will validate these associations across the Alzheimer’s disease spectrum.
Simplify scales for identifying AD and MCI: A machine learning study based on six years of database
Authors: Lü Wenqi , Zhang Meiwei , Kuang Weihong , Lü Yang 
Published: June 2023

AbstractBackgroundAlzheimer’s Disease (AD) is a neurodegenerative disorder characterized by cognitive functional decline accompanied with neuropsychiatric symptoms and impairment of activities of daily living (ADL). Mild Cognitive Impairment (MCI) is considered the prodromal state of AD. Early identification of MCI is a strategy to reduce the burden of caregivers and society. Neuropsychological scales are still the most used method for identification of cognitive decline. The purpose of this study was to simplify the scales by eliminating some insensitive items based on the six years of database and machine learning methods.MethodA total of 458 patients newly diagnosed as AD or MCI were recruited in Memory Clinic, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University from 2014 to 2019. Neuropsychological battery was used to evaluate the cognitive function, neuropsychiatric symptoms and ADL, including Mini‐mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS), Boston Naming Test (BNT), Digit Span (DS), Auditory Verbal Learning Test (AVLT), Trail Marking Test (TMT) A and B. Alzheimer’s Disease Assessment Scale (ADAS‐cog), Clinical Dementia Rating (CDR), Instrumental Activity of Daily Living Scale (IADL), Physical Self‐Maintenance Scale (PSMS). XGboost and CART regression tree were used to test all items contained in all scales and try to explore the importance of each item. Sensitivity was reflected by the AUC (Area Under Curve).ResultOf which 236 patients were diagnosed as AD and 222 as MCI. The mean age was 72.99±9.04 years and 51.53% were male. Among all the battery items, ADAs‐cog word recognition task showed the best importance in judging AD and MCI, followed correct numbers of AVLT delay recall, ADAs‐cog orientation, MMSE recall, TMT‐B time. The overall sensitivity for predicting AD or MCI for all items was 0.83. However, in our preliminary screening also showed the 31 items, most of which were based on the ADL scale and neuropsychiatry symptoms, contributed little to distinguishing AD from MCI. After removed these items, the sensitivity became to 0.87.ConclusionCognitive assessment such as recall and orientation may be a better strategy than neuropsychiatric symptoms and ADL when identifying AD from MCI.
Single vascular insult exacerbates disease pathology in APPswe Mice.
Authors: Diwakar Latha , Hussain Rehab , Ravindranath Vijayalakshmi 
Published: June 2023

AbstractBackgroundVascular insults, such as microinfarcts play a major role in mixed dementia including Alzheimer’s disease (AD). Neuroimaging from longitudinal studies have shown involvement of white matter hyperintensities due to blood brain barrier (BBB) breakdown. In patients with AD the combined neurotoxic effects of amyloid‐β (Aβ) converge on brain vasculature synergistically leading to neuronal and synaptic dysfunction, which in turn leads to cognitive impairment. In the present study we examined the effect of vascular insult induced by enothelin‐1 (ET‐1, a vasoconstrictor peptide) on Aβ pathology in mouse models of AD. We further studied behavioral deficits during reduced cerebral blood flow changes and structural changes in BBB components.MethodWe injected 2µg/2μl of ET‐1 bilaterally into lateral ventricles APPswe mice carrying point mutation for APP. Behavioral assays were performed to compare associative learning and spatial memory deficits, if any after 30 days of ET‐1 injection. Immunohistochemistry for markers of endothelial cells and pericytes were done to look at the structural changes in BBB. Aβ ELISA and plaque load were tested to understand the effect of vascular insult on AD pathology.ResultVasoconstriction following ET‐1 injection after 30 days leads to memory deficits in AD mice while wildtype mice recovered. There were structural changes in BBB showing decreased expression of endothelial and pericyte marker, however these changes were not observed in wildtype mice. Aβ levels were increased in brain lysates of APPswe mice injected with ET‐1.ConclusionSingle vascular insult was adequate to bring about impairment in learning and memory in APPswe mice and structural changes in BBB, which were not seen in WT type mice indicating that ET‐1 induced cerebral hypoperfusion accelerated AD pathogenesis.
Investigating ADHD and ASD features in dementia patients referred to a memory clinic in Iran
Authors: Mohammadian Fatemeh , Motamed Mahtab , Zavieh Amir , Heidari Arash 
Published: June 2023

AbstractBackgroundDementia is a clinical syndrome characterized by a progressive cognitive decline interfering with the function of activity of daily living in patients (1). Autism spectrum disorder (ASD) and Attention deficit hyperactivity disorder (ADHD) are two prevalent neurodevelopmental disorders affecting different brain functions manifesting mostly with impaired communication and behavior (3). These disorders initiate in childhood but usually persist into adulthood (3, 4). These disorders might overlap with dementia symptoms, as they might share common genetic and environmental backgrounds (5‐7). ASD and ADHD in dementia patients may complicate the timely diagnosis of each disorder leading to more pronounced dysfunction. Hence, this study aimed to evaluate ASD and ADHD symptoms in dementia patients referred to a memory clinic in Iran.MethodWe recruited 65 dementia patients in this study. Firstly, a cognitive neurologist diagnosed dementia’s subtypes by a precise clinical examination, cognitive assessment by applying the Montreal cognitive Assessment (MoCA). The severity of dementia was determined using the Functional Assessment Staging Tool (FAST). Consequently, we instructed the participants to fill out the autism quotient (AQ) and the Conners' Adult ADHD Rating Scales (CAARS) questionnaires for investigating their ASD and ADHD symptoms.ResultConsidering the cut‐off points of AQ and CAARS questionnaires, 18.5% of participants were diagnosed with ASD, and 35.4% were diagnosed with ADHD. Besides, we found a significant positive relationship between all subscales of CAARS and the FAST score (P < 0.05). In other words, patients with more severe dementia were more likely to have increased ADHD symptoms.ConclusionThe results indicated that ADHD and ASD symptoms might be common manifestations in patients with dementia. This finding was in line with the previous research findings regarding the high co‐occurrence of ADHD and dementia (8). This comorbidity can further prohibit function and further worsen the prognosis. Given that there is scarce evidence on the association between ADHD and dementia in Iran, the findings of this study can pave the way for future research to elaborate more precisely on the etiological backgrounds of this association.
Micro and macro‐linguistic analysis of narrative discourse in Moroccan patients with Alzheimer’s Disease
Authors: Taiebine Mohamed , Faris Mustapha El Alaoui 
Published: June 2023

AbstractBackgroundThe production of narrative discourse or connected speech implies dynamic and complex functions at different levels of neuro‐cognitive, micro (parts of speech) and macro‐linguistic processing (cohesion and coherence). Such functions are classically impaired in Alzheimer’s disease (AD). Several studies have described these impairments in European languages; however, no study has characterized them in terms of neuro‐psycholinguistic patterns in Arabic.MethodWe studied the speech sample of six patients with moderate Alzheimer’s disease from the Alzheimer’s Center in Rabat. They described orally the picture of cookies theft subtest (BDAE). They meet the clinical criteria for AD (McKhann, 2011). The average age is 69 years (SD: 5.9; 61‐77) and of education is 13.6 years (SD: 2.3; 9‐15), duration of the disease is 5 years (SD 2.09; 3‐8). The neuropsychological assessment has been carried out with MoCA (Montréal Cognitive Assessment), MIS (Memory Impairment screen), Fluency tasks and Clock drawing test. Regarding discourse analysis and psycholinguistic variables, we used the method which has been described by Croisile (1996) and Boschi et al (2017).ResultThe neurolinguistic assessment showed an impairment of macro‐linguistic variables. The effectiveness of speech was clearly one of the most impaired variables as well as the syntactic complexity in the majority of patients. Cohesion has been lower than local and global coherence. These macro‐linguistic performances revealed a pragmatic dysfunction as part of the neuropsycho‐linguistic profile of our patients depending on their disease duration. However, at a micro‐linguistic level, functional words and verbs were the most produced in oral description compared to nouns, adjectives and adverbs. Such results might evoke the hypothesis of an impairment of explicit linguistic knowledge which involved different intra and inter‐linguistic systems in AD.ConclusionThe wide range of cognitive‐linguistic impairments which has been highlighted during the cookie theft picture description, showed the importance of assessing micro and macro‐linguistic impairments in narrative speech in Moroccan patients with AD. Such linguistic task is an added‐value to formal assessments and follow‐up of cognitive decline in AD.
Brazilian version of Northwestern university famous faces test (NUFFACE‐Br): Evidence of validity between control and clinical groups
Authors: Proença Mirela Silva , da Silva Filho Silvio R. B. , Moriguti Julio , Tumas Vitor , Foss Maria Paula 
Published: June 2023

AbstractBackgroundNUFFACE was created to identify the locus of name‐face failure common in healthy aging and dementia. Psychometric studies are necessary for the development of the Brazilian version. Therefore, we intend to verify the evidence of predictive (or diagnostic) validity of this instrument.Methodsa total 24 participants were included in this study and divided into 12 cognitively healthy elderly (NC) and 12 with dementia due to Alzheimer’s Disease (AD; CDR‐1). All responded to the NUFFACE‐Br, which has four tasks: 1) facial naming; 2) verbal description of the facts related to the face; 3) verbal description in response to the printed name; and 4) face‐name matching (multiple‐choice format). Different types of errors, such as Semantically Related (SR), Semantically Unrelated (SU), Phonological Similarity (Ph), “I don’t know” (DK), and Others (O), were developed as part of the correction criteria. The comparison of sociodemographic variables and NUFFACE‐Br total tasks were performed by Mann‐Whitney U test, adopting a significance level of 5%.ResultsThe groups did not differ by age, education, and sex (p<0.05). The NC performed better than the AD in almost all tasks of this instrument (p<0.01), except for task 4 (p<0.266). The AD presented more difficulty in the naming faces tasks (average = 14±6.6) than the others and similar performance to the NC in the face‐name correspondence (average score = 30.7±2.1). A higher frequency of all types of errors was verified in the AD group for the first three tasks of this instrument, except for the “phonological similarity,” in which the frequency of errors was the same between the groups. Task 4 presented a higher frequency in SR, SU, and O errors.ConclusionSignificant differences were verified between the NC and AD groups, indicating the predictive (or diagnostic) evidence of NUFFACE‐Br. The face‐name matching task was the only one that did not show differences between the groups. The AD presented a higher frequency of errors when compared to the NC, especially in the task of naming faces. Further psychometric studies are being conducted to elucidate the clinical evidence of this instrument to old Brazilian adults.