bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing a tool for assessment of infographics aimed at people living with Vascular Dementia
Authors: Harkness Kirsty , Dean Laura , Thompson Celia , Nesbitt Graham , Craig Claire , Bell Simon M 
Published: December 2023

AbstractIntroductionPeople living with vascular dementia (VaD) have an altered neuropsychological profile, including visuospatial deficits, decreased attention, altered colour perception and executive function problems. Because of this, they perceive and interpret information differently, thus we cannot assume that they read and absorb information in the same format as cognitively healthy individuals. This paper reviews current infographics available for patients with VaD and the appropriateness of information delivery within these documents.MethodsA literature review identified the ideal features of infographic design that allow people living with VaD to engage with the infographic. Many of these ideal infographic features are not found within existing VaD resources. We developed a rating scale for the construction of future infographics, and infographic examples to ensure optimal accessibility and understanding for people living with VaD. A questionnaire was distributed to dementia clinicians across the UK to validate the scoring system and assess their views on current infographics available. A focus group of people living with dementia and their carers reviewed prototype infographics and fed back to the research team about how best to use infographics in dementia care.ResultsThe literature review suggested the most important factor that determines ability of an infographic to transfer information to people living with VaD was text formatting. Of 164 clinicians the questionnaire was distributed too, we had 36 respondents (22% response rate) across 9 health care occupations. 35 (97%) believed that infographic material is useful in the memory clinic setting but only 21(58%) use these resources. Care providers felt that the most important feature of infographic design is the use of graphics (56.3%), followed by language (37.5%). The general consensus was that information should be kept simple, concise and complemented by pictures, and patients should be involved in infographic development to incorporate their opinions. Patient groups identified that having infographic information that evolved in complexity as the disease progressed would be best for patients.ConclusionWe have developed a framework for infographic design specifically aimed at those living with VaD. This framework can be used to develop infographics best suited to the altered neuropsychological profile in VaD.
The impact of COVID‐19 lockdown on mortality rate in memory clinic patients
Authors: Bakker Els D. , Zwan Marissa D. , Gillissen Freek , Bouwman Femke H. , Pijnenburg Yolande A.L. , van der Flier Wiesje M. , van Maurik Ingrid S. , van der Veere Pieter J. 
Published: December 2023

AbstractBackgroundPeople with (pre‐)dementia were particularly at risk for mortality during the COVID‐19 pandemic due to severe outcome of a COVID‐19 infection and the negative consequences of restrictive measures. Here we study whether patients during the COVID‐19 pandemic had a higher mortality rate compared to historical controls.MethodIn this case‐control study, we included patients from the Amsterdam Dementia Cohort: 1) Pandemic patients (n = 1022) with a baseline visit between January 2017 and December 2018 and 2) Historical controls (n = 930) with a baseline visit between January 2015 and December 2016. Both groups were followed for three years (pandemic patient until 2021 and historical controls until 2019). Absolute standardized mean differences were analyzed in order to determine whether groups were well‐balanced in terms of demographics and cognition at baseline. Cox proportional hazards analyses were performed to compare mortality rate during COVID‐19 pandemic with historical controls. Age, sex, diagnosis, MMSE score, education level, and comorbidity were added as covariates to the model.ResultBoth groups were well‐balanced, as mean age of the pandemic patients was 63±9 years, n = 423 (41%) were female and mean MMSE score was 24.5±5.0. Mean age of the historical controls was 63±8 years, n = 404 (43%) were female and MMSE score was 24.2±5.2. The absolute standardized mean differences were under 0.1 for all selected covariates. Among the pandemic patients, n = 180 (18%) patients died during the previously described follow‐up time. In the historical control group, n = 131 (14%) patients died. Cox proportional hazards models showed that pandemic patients had higher risk for mortality than historical controls (HR [95%‐CI] = 1.27 [1.02‐1.59]). Results remained significant after adjusting for covariates age, sex, diagnosis, MMSE score, education level, and comorbidity (HR [95%‐CI] = 1.37 [1.09‐1.72]).ConclusionMemory clinic patients had increased risk on mortality during times of COVID‐19 lockdown compared to historical controls. This indicates that COVID‐19 lockdown regulations have accelerated disease. Even though the cause of mortality is unknown, it is likely that the excess mortality is not only due to COVID‐19 infections, but also caused by the restrictive measure of the COVID‐19 lockdown restrictions (e.g. social isolation and loss of structure).
Effects of enlarged perivascular space in Parkinson’s disease and related cognitive decline
Authors: Kanekar Sangam , Du Guangwei , Chen Hairong , Maffie Jonathan , Lewis Mechelle , Kong Lan , Huang Xuemei 
Published: December 2023

AbstractBackgroundThe glymphatic system plays a key role in brain toxics clearance. Many studies demonstrated that disrupted glymphatic system is responsible for insufficient clearance of Aβ and tau protein in Alzheimer’s disease. Its contribution in Parkinson’s disease (PD) and related cognitive function decline has not been fully studied. Enlarged perivascular space (PVS) may be a sign of glymphatic function decline, hence leading to PD pathology and PD‐related cognitive function decline. Our objective was to study the PVS in PD and related cognitive function decline.MethodHigh‐resolution T1‐weighted and T2‐weighted MRI data were acquired from 60 PD patients and 58 age‐ and sex‐matched controls. The PVS from the centrum semiovale of the white matter (CS), striatum (ST) and midbrain (MB) of the basal ganglia were segmented using the enhanced images from T1‐ and T2‐weighted images. Total intracranial volumes (TIV) were obtained to account for individual head sizes. Montreal Assessment of Cognition (MoCA) was used to quantify cognitive function. MDS‐UPDRS III scores were obtained for motor function deficits. ANCOVA was used to compare PVS metrics between PD patients and controls adjusted for age, sex, and TIV. Multiple regression was used to corelate PVS metrics and MoCA in PD patients with age, sex, MDS‐UPDRS III score and TIV as covariates.ResultCompared to controls, PD patients had enlarged PVS in MB (p = 0.0028), but not in CS and ST. PVS metrics were strongly associated with age (p < 0.0001 for CS, p < 0.0001 for ST, and p = 0.0092 for MB), but only PVS in MB was associated sex (p = 0.0001). In PD patients, the MoCA was associated with the PVS in CS (p = 0.0132), MB (p = 0.0275) and total PVS (p = 0.0088) but only trending with PVS in ST (p = 0.0737). There is no association between MoCA and PVS metrics in controls.ConclusionOur findings suggested that PD patients have enlarged PVS in the midbrain, and their cognitive function is associated with enlarged PVS in both CS and MB. The enlarged PVS might be an etiological factor for PD pathology and related cognitive decline.
Computerized decision support is an effective approach to select memory clinic patients for amyloid‐PET
Authors: Rhodius‐ Meester Hanneke F.M. , van Maurik Ingrid S. , Collij Lyduine E. , van Gils Aniek M. , Koikkalainen Juha , Tolonen Antti , Pijnenburg Yolande A.L. , Barkhof Frederik , van de Giessen Elsmarieke , Lötjönen Jyrki , van der Flier Wiesje M. 
Published: December 2023

AbstractBackgroundThe use of amyloid‐PET in daily clinical practice is upcoming. Yet, ttranslation of the appropriate use criteria (AUC) to clinical practice is challenging, hampering successful implementation of amyloid‐PET. Tools that guide selecting patients for whom amyloid‐PET has most clinical utility are needed. Therefore, we developed and evaluated a computerized decision support approach to select patients for amyloid‐PET testing.MethodWe included 286 subjects (136 controls, 116 Alzheimer’s disease (AD) dementia, 26 frontotemporal lobe dementia (FTD), and 8 vascular dementia (VaD) from the Amsterdam Dementia Cohort, with available neuropsychology, APOE, MRI and [18F]florbetaben amyloid‐PET. In our computerized decision support approach, we first classified the subjects using only neuropsychology, APOE, and MRI data. Then, for uncertain subjects (probability of correct class (PPC) < 0.75) we tested the classification by adding amyloid positive (AD like) and negative (normal) visual PET read results, and assessed whether either of the values makes the diagnosis reliable (PPC≥0.75). If the threshold of PCC was reached, the actual visual PET read result was used in the final classification. We compared the proportion of PET scans and patients diagnosed with sufficient confidence (PPC ≥0.75) in the computerized approach with three scenarios: 1) without amyloid‐PET (only demographics, neuropsychology, APOE and MRI), 2) amyloid‐PET according to the AUC and 3) amyloid‐PET for all patients. The study was performed using five‐fold cross‐validation.ResultThe computerized approach advised PET in n = 76(27%) patients, leading to a diagnosis with sufficient confidence in n = 190(66%) patients. This approach outperformed the other three scenarios: 1) without amyloid‐PET, diagnosis was obtained in n = 147(51%), 2) applying the AUC resulted in amyloid‐PET in n = 113(40%) and diagnosis in n = 160(56%), and 3) performing amyloid‐PET in all patients resulted in diagnosis in n = 165(58%).ConclusionOur computerized data‐driven approach restricted the application of amyloid‐PET to 27% in a memory clinic cohort of controls, AD, FTD, and VaD, without compromising diagnostic accuracy. This approach can support clinicians in making a balanced decision in ordering additional biomarker testing during the dementia workup. Thus, innovative use of resources can be stimulated, which is essential when disease‐modifying drugs increase the demand for biomarker testing.
Longitudinal changes of amyloid (A) and tau (T) image‐based biomarker in Alzheimer’s disease spectrum
Authors: Kim Han‐Kyeol , Cho Hanna , Lee Jae Hoon , Chun Joong‐Hyun , Ryu Young Hoon , Lyoo Chul Hyoung 
Published: December 2023

AbstractBackgroundTo investigate long‐term changes in dichotomous profiles of amyloid (A) and tau (T) image‐based biomarker in Alzheimer’s disease (AD) spectrum.MethodDuring the initial visit (V1), a total of 275 participants [96 cognitively unimpaired (CU), 108 mild cognitive impairment (MCI), and 71 AD] who completed 18F‐florbetaben and 18F‐flortaucipir PET studies were followed up to three times. Two years later, 189 participants (74 CU, 77 MCI, and 38 AD) were enrolled in the second visit (V2), and 83 participants (34 CU, 39 MCI, and 10 AD) were enrolled in the third visit (V3) five years later (mean 4.8 years) to complete the same PET studies. The A and T biomarker profile was determined based on the cut‐off standardized uptake value ratio of the most vulnerable region in each pathology.ResultIn A‐ participants, 5.4% (6/111) of participants converted to A+ at V2 and 17.9% (7/39) converted to A+ at V3. Likewise, 2.9% (4/138) of participants in T‐ participants converted to T+ at V2, and 17.7% (11/62) converted from T‐ to T+ at V3. Compared to the low conversion rate from T‐ to T+ in A‐T‐ participants [0.9% (1 A‐T+ / 106 A‐T‐) at V2 and 5.1% (2 A+T+ / 39 A‐T‐)] at V3, A+T‐ participants showed higher conversion rates from T‐ to T+ [9.4% (3 A+T+ / 32 A+T‐) at V2 and 39.1% (9 A+T+ / 23 A+T‐) at V3].ConclusionThe conversion of the at biomarker profile was observed more prominently in the long term than in the short term, and the conversion of the T biomarker in A+ compared to A‐ was over seven times more frequent in five years follow‐up.
Genetic dissection of Hippocampal sclerosis MRI surrogates
Authors: Olivé Clàudia , de Rojas Itziar , Zhang Linda , Sotolongo‐Grau Oscar , Quintela Inés , García‐González Pablo , García‐Sánchez Ainhoa , Puerta Raquel , Valero Sergi , Cano Amanda , Calero Miguel , Rabano Alberto , Pastor Ana Belén , Ser Teodoro , Medina Miguel , Sanchez‐Juan Pascual , Strange Bryan A , Carracedo Angel , Marquié Marta , Tárraga Lluís , Boada Mercè , Ruiz Agustin 
Published: December 2023

AbstractBackgroundHippocampal sclerosis of aging (HS) is one of the most predominant causes of dementia in elder populations and it is often misdiagnosed as Alzheimer’s disease (AD). HS has recently been found to show a hippocampal atrophy pattern that might be key for the differentiation of this pathology from AD in the early stages of dementia.MethodIn this study, we aimed to find SNPs associated with AD diagnosis that might be related to HS. To that end, we calculated a polygenic risk score (PRS) combining SNPs associated with AD by Bellenguez et al. (2022) and assessed their relation with HS‐by‐proxy based on magnetic resonance imaging (MRI) data of hippocampal subfield volumes from 1,130 individuals without dementia syndrome.ResultOur results show a significant association of AD‐PRS with fimbria and hippocampal body and head volumes. Association with these hippocampal subfields was also observed on the individual effects of the AD‐related variants in the SHARPIN (rs34173062) and TNIP1 (rs871269) genes. Besides, these loci remained consistently associated to HS‐aging after increasing the sample size by including an independent cohort of healthy individuals (N = 729).ConclusionThe results presented in this study suggest that some SNPs that have recently been identified as AD variants might be closely related to atrophy in hippocampal subfields instead of AD, and hence, could be instrumental to refine AD and HS pathways, their interrelationships, and to elaborate specific treatment for each condition.
Repetitive transcranial magnetic stimulation increases synaptic plasticity of cortical axons in the APP‐PS1 mouse model of amyloidosis
Authors: Fulopova Barbora , Bennett William , Canty Alison Jane 
Published: December 2023

AbstractBackgroundRepetitive transcranial magnetic stimulation (rTMS) is non‐invasive brain stimulation with therapeutic potential for use in diseases causing dementia. We previously demonstrated that low intensity (LI) rTMS induced functional improvements in the accuracy and rate of learning in adult mouse skilled reaching paradigms (Tang, Bennett et al, Scientific Reports, 2018) and induced dendritic spine changes in cortical motor neurons after a single application of LI‐rTMS (Tang, Bennett et al, Brain Stimulation, 2021). Here, we investigate the effect of LI‐rTMS on axonal boutons of excitatory axons in the presence of amyloid pathology in the APP‐PS1 mouse.MethodAPP/PS1 mice were crossed with Thy1‐GFPM mice to visualise excitatory axon circuitry in the presence of amyloid plaque pathology. Multiphoton imaging through a cranial window was used to identify cortical axons in the upper layers of the sensorimotor cortex in adult animals (10‐12 months old) and monitor the stability and turnover (gains and losses as a fraction of total number of synapses) of axonal boutons in the presence (APP‐GFPM) or absence (WT‐GFPM) of amyloid pathology. Axons were imaged at 48‐hour intervals for 8 days either side of a single session of LI‐rTMS.ResultThe density of axonal boutons along the axon shaft was stable and comparable in APP‐GFPM and WT‐GFP mice, before and after LI‐rTMS. The turnover of synapses was significantly (p < 0.05) reduced in APP‐GFPM cortical axons compared to WT‐GFPM prior to stimulation. A single session of LI‐rTMS induced a significant (p < 0.01)and sustained increase in synaptic turnover in both genotypes. Interestingly the initial lower turnover of boutons in the APP‐GFPM cortex was increased to the levels observed in WT‐GFPM axons at baseline.ConclusionIn the presence of amyloid pathology, synaptic density in excitatory cortical axons is unchanged, however the dynamic fraction of synapses is reduced in compared to aged‐matched controls. LI‐rTMS boosts synaptic plasticity in mature cortical axons in both the presence and absence of plaque pathology. Together with our findings of improved functional performance following stimulation, these results suggest not only possible mechanisms of action but also a potential clinical benefit in the management of Alzheimer’s disease.
Benzodiazepine use in relation to long‐term dementia risk and imaging markers of neurodegeneration: a population‐based cohort study.
Authors: Hofe Ilse E. M. , Stricker Bruno H. , Vernooij Meike W , Ikram M. Kamran , Ikram M. Arfan , Wolters Frank J. 
Published: December 2023

AbstractBackgroundBenzodiazepine use is common, particularly in older adults. Benzodiazepines have well‐established acute adverse effects on cognition. However, long‐term effects on dementia risk remain uncertain, and on subclinical imaging markers of neurodegeneration largely undetermined.MethodWe included 5443 cognitively healthy participants (MMSE≥26) from the population‐based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005‐2008) was derived from ATC‐coded pharmacy records, from which we determined drug type (anxiolytics vs. sedative‐hypnotics vs. both) and cumulative dose. We determined the association of benzodiazepine use with dementia risk until 2020 using Cox regression, and with change in neuroimaging markers during 5‐yearly repeated brain MRI using linear mixed models. Models were adjusted for demographics, lifestyle factors and comorbidity, including presence of anxiety, depression and sleeping problems.ResultDuring a mean follow‐up of 11.2 years, 726 participants (13.3%) developed dementia. Benzodiazepine use occurred in 1675 (30.8%) participants, of whom 845 (50.4%) had used anxiolytics, 390 (23.3%) had used sedative‐hypnotics, and 440 (26.3%) had used both. Current use of any type of benzodiazepine at baseline, but not former use, was associated with an increased dementia risk during follow‐up (HR[95%CI] for current users: 1.56[1.17‐2.09]; and past users: 1.07[0.87‐1.31]). Excess risk in current users persisted after excluding a 2‐year lag‐time of benzodiazepine use prior to baseline. Dementia risk was dependent on cumulative dose (>median: HR[95%CI] 1.31[1.05‐1.63] vs. < = median: HR[95%CI] 1.01[0.78‐1.31]). Use was not associated with volume of grey matter, white matter, hippocampus, amygdala or thalamus at baseline. During follow up, high cumulative dose was associated with accelerated decrease in hippocampal volume (p = 0.021). Regarding drug type, dementia risk was increased with anxiolytics (overall HR[95%CI]: 1.37[1.10‐1.71]), which was paralleled by accelerated atrophy of grey matter (p = 0.036), albeit no dose‐response relationship was observed. Sedative‐hypnotics were not associated with dementia risk or brain atrophy. Combined use of anxiolytics and sedative‐hypnotics at baseline was associated with increased dementia risk (HR[95%CI]: 1.70[1.05‐2.76]), but this attenuated after excluding use during a 2‐year lag time before baseline (HR[95%CI]: 1.08[0.71‐1.64]), and was not associated with brain atrophy.ConclusionChronic use of benzodiazepines in a population of cognitively healthy older adults is associated with increased dementia risk.
A DIAGNOSIS APPROACH FROM DIFFERENT NATURE BIOMARKERS TO PREDICT THE ALZHEIMER DISEASE RISK
Authors: Cháfer‐Pericás Consuelo , Álvarez Lourdes , Peña‐Bautista Carmen , Ferré‐González Laura , Lara Sergio , Deltell Anabel Forte , Baquero Miguel 
Published: December 2023

AbstractBackgroundAlzheimer Disease (AD) diagnosis requires invasive and expensive techniques (cerebrospinal fluid (CSF) biomarkers, neuroimaging), which could not be extended to general population. So, minimally‐invasive, specific and accurate AD diagnosis are needed. Recent studies have identified blood compounds (lipid peroxidation compounds, lipids, proteins…) as potential diagnosis biomarkers. Therefore, research focused on the development of diagnosis models from different nature blood biomarkers is required, allowing to obtain information about the molecular mechanisms in AD. In this sense, the present study consists of the study of different plasma biomarkers (lipids, lipid peroxidation metabolites, microRNAs) impairment, and the development of a potential diagnosis model.MethodParticipants provided informed consent, these are patients who come to the neurology unit with memory complaint. They were neuropsychologically evaluated, and cerebrospinal fluid samples (CSF) were obtained to determine some biomarkers (β‐amyloid‐42, β‐amyloid‐40, p‐Tau, t‐Tau, neurofilament light chain). A total of 85 participants, aged 50 to 79 years, were included in this study. They were classified into early AD patients (mild cognitive impairment (MCI), mild dementia), other dementias (frontotemporal dementia, Lewy body dementia, vascular dementia) and people cognitively healthy. Also, blood samples were taken to determine some potential biomarkers (lipid peroxidation compounds, microRNAs) by means of mass spectrometry and quantitative PCR. Finally, statistical Bayesian analysis were carried out to develop the optimum diagnosis model.ResultSome lipids, lipid peroxidation compounds and microRNAs showed different blood levels among participants groups. From these results, and considering the variables Bayesian selection (18_0_Lyso_PC, 16_0_SM, 18_0_SM, total neuroprostanes, total isoprostanes), it was developed the optimum model to predict early AD. This model showed satisfactory diagnosis indexes.ConclusionDifferent nature biomarkers are involved in AD development, reflecting the complex disease physiopathology. Therefore, a multi‐nature biomarkers approach could provide a useful tool for early and minimally invasive screening.