bluuebunny/crossref_metadata_2025_split huggingface dataset:
A longitudinal analysis of cerebral blood flow changes in genetic frontotemporal Dementia: Results from genfi
Authors: Pasternak Maurice , Mirza Saira S. , Mutsaerts Henk‐Jan , Thomas David L , Cash David M , Bocchetta Martina , de Vita Enrico , Tartaglia Carmela , Mitchell Sara Berman , Black Sandra E. , Freedman Morris , Tang‐Wai David F. , Rogaeva Ekaterina , van Swieten John C. , Laforce Robert , Tagliavini Fabrizio , Borroni Barbara , Galimberti Daniela , Rowe James B , Graff Caroline , Finger Elizabeth , Sorbi Sandro , de Mendonça Alexandre , Butler Christopher , Gerhard Alexander , Sanchez‐Valle Raquel , Moreno Fermin , Synofzik Matthis , Vandenberghe Rik , Ducharme Simon , Levin Johannes , Danek Adrian , Otto Markus , Santana Isabel , MacIntosh Bradley J. , Rohrer Jonathan D. , Masellis Mario 
Published: June 2023

AbstractBackgroundMutations in the C9orf72, GRN, or MAPT genes are the most prevalent genetic causes of familial frontotemporal dementia (FTD). In a cross‐sectional study of genetic FTD, lower CBF was observed in presymptomatic FTD mutation carriers vs. controls from the same families in 6 regions of interest: the bilateral anterior cingulate cortex, the left medial temporal gyrus, the left and right insulae, and the left and right supramarginal gyri (Mutsaerts et. al. 2019). However, there have been no studies to date that identify longitudinal changes in CBF between FTD genetic subgroups (both presymptomatic and symptomatic) compared to controls.MethodWe compared longitudinal changes in CBF, as measured by ASL‐MRI, in 317 FTD mutation carriers (118 C9orf72, 141 GRN, and 58 MAPT) vs. 261 non‐carrier controls from the Genetic FTD Initiative (GENFI). Linear mixed effects models tested the main effect of carrier status, and its interaction with age, along with covariates of age, sex, site‐of‐scan against each subject’s mean regional cerebral blood flow within the regions of interest from Mutsaerts et al. (2019). Family membership was a random intercept in the model to control for similar genetic and environmental backgrounds.ResultDifferences between genetic subsets of FTD were apparent, with GRN carriers preferentially experiencing decreases within the salience network regions while MAPT carriers expressed differences within the left medial temporal gyrus and bilateral anterior cingulate gyrus. C9orf72 carriers only saw a decrease in CBF within the left insula. Significant interactions between carrier status and age were exclusively evident in MAPT carriers across all regions of interest.ConclusionDifferentiating CBF signatures were found to exist between the genetic FTD subgroups, with the most prominent changes being seen in GRN and MAPT subsets. Evidence continues to mount that CBF may be a viable biomarker in the earlier detection and delineation of genetic FTD variants.References: Mutsaerts, H. J. M. M. et al. Cerebral perfusion changes in presymptomatic genetic frontotemporal dementia: a GENFI study. Brain 142, awz039 (2019).
Changes of basal forebrain volume along the Alzheimer’s disease continuum in Down syndrome
Authors: Aranha Mateus Rozalem , Iulita Maria Florencia , Montal Victor , Pegueroles Jordi , Bejanin Alexandre , Grothe Michel J. , Carmona‐Iragui Maria , Videla Laura , Benejam Bessy , Valldeneu Sílvia , Barroeta Isabel , Altuna Miren , Fernandez Susana , Ribas Laia , Padilla Concepcion , Alcolea Daniel , González‐Ortiz Sofía , Bargallo Núria , Busciglio Jorge A , Cuello A. Claudio , Wisniewski Thomas , Blesa Rafael , Lleó Alberto , Fortea Juan 
Published: June 2023

AbstractBackgroundAtrophy of basal forebrain (BF) cholinergic neurons is an early event in Alzheimer’s disease (AD) and is associated with cognitive impairment. Down syndrome (DS) is now recognized as a genetically determined form of AD. Therefore, people with DS represent a priority population to study biomarkers of AD pathology and neurodegeneration. Degeneration of BF neurons occurs both in sporadic AD and in DS brains with advanced AD pathology. However, the dynamics of BF atrophy and its changes with age and AT(N) biomarkers have not been studied in DS.MethodWe included 246 adults with DS (mean age 43.2 ±11.0 years; 43% female). Volumes of antero‐medial and posterior areas of the BF (amBF and pBF, respectively) were extracted from T1‐weighted 3T MR images using voxel‐based morphometry in SPM12 in combination with a stereotactic atlas of BF functional subdivisions (Figure 1). Differences in amBF and pBF volume in each AD clinical stage (Asymptomatic, Prodromal and Demented) were assessed with Kruskall‐Wallis and pairwise Wilcoxon tests. The relationship of BF volumes with age and AT(N) biomarkers in the cerebrospinal fluid (CSF) (amyloid‐β 42/40 ratio [aβ ratio], phosphorylated Tau 181 [pTau], total Tau [tTau] and neurofilament light [NFL]) was assessed in a subset of subjects (n = 161 [aβ ratio, pTau and tTau] and n = 95 [NFL]) with locally estimated scatterplot smoothing (LOESS) and linear regression in R, respectively.ResultVolumes of amBF and pBF decreased significantly with age (Figure 2), with a steeper decline during the fifth decade of life. BF volumes also declined with AD clinical stage (Figure 3), and had significant correlations with CSF aβ ratio (p<0.001 r2 = 0.22), pTau (p<0.001 r2 = 0.20), tTau (p<0.001 r2 = 0.20) and NFL (p<0.001 r2 = 0.33) (Figure 4).ConclusionIn DS, BF volume decreases with age, AT(N) biomarkers and along the cognitive stages of the AD continuum.
Interference of different anesthetic agents on behavior and oxidative stress in the animal model of Aβ1‐42‐induced dementia in mice.
Authors: Garcez Michelle Lima , Macarini Bárbara Machado Naspolini , Medeiros Eduarda Behenck , Vargas Adrielly , Colombo Ana Carolina Nunes , Boaventura Amanda L , Zabot Gabriel Casagrande , Keller Gabriela Serafim , Rempel Lisienny Campoli Tono , Silveira Paulo Cesar Lock , Budni Josiane 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease. The animal model of AD‐like dementia induced by the peptide β‐amyloid 1‐42 (Aβ1‐42) is widely used. However, the animals have to be anesthetized and no studies are evaluating which anesthetic causes less interference in this model. This study aimed to evaluate the interference of different anesthetics on behavioral and oxidative stress in a mice model of Aβ1‐42‐induced dementia.MethodMale and female BALB/c mice at 3‐ month‐old were used under three different protocols. Protocol 1 (inhalation): (1) 100% oxygen (isoflurane control); (2) artificial cerebrospinal fluid (ACSF) + isoflurane; (3) Aβ1‐42 + isoflurane. Protocol 2 (intraperitoneal): (1) saline; (2) ACSF + ketamine + xylazine; (3) ACSF + ketamine + dexmedetomidine; (4) Aβ1‐42 + ketamine + xylazine; (5) Aβ1‐42 + ketamine + dexmedetomidine. Protocol 3 (intraperitoneal): (1) saline; (2) ACSF + propofol; (3) Aβ1‐42 + propofol. After the anesthesia, mice were injected with Aβ1‐42 (400 pmol) free‐hand intracerebroventricular, then after 13 days, mice were submitted to the Y‐maze test (spatial memory), plus‐maze (anxiety), and open‐field (habituation memory); then, hippocampus were dissected to analysis.ResultIsoflurane per se (protocol 1) caused no memory impairment, but caused an anxiolytic effect in males, in addition, to increased sulfhydryl content in males. In protocol 2, ACSF + ketamine + xylazine induced spatial memory impairment in males and habituation memory impairment in females; the anesthetics of protocol 2 increased 2',7' dichlorodihydrofluorescein (DCF) levels in females, and ACSF + ket + dex reduced levels of glutathione (GSH) in males. In protocol 3, propofol per se caused an anxiolytic effect in males and increased DCF levels in males and females, increased superoxide dismutase activity in males, and reduction in females, in addition, increased sulfhydryl content in males.ConclusionAll anesthetic protocols evaluated caused alterations in the behavior and/or oxidative stress parameters; however, isoflurane seems to cause less interference in the animal model, followed by propofol. Protocol 3 seems to cause more interference, including in the Y‐maze (spatial memory), which is one of the main behavior tests to evaluate the mice model of Aβ1‐42‐induced dementia.
Impact of serum leptin and adiponectin levels on the development of brain infarcts in patients with mild cognitive impairment and Alzheimer’s disease
Authors: Carbone Giovanni , Palaia Maria Emiliana , Ercolano Erica , Santoro Maria Angela , Scognamiglio Francesco , Bencivenga Leonardo , Vitale Dino Franco , Rengo Giuseppe , Femminella Grazia Daniela 
Published: June 2023

AbstractBackgroundThe adipokines leptin and adiponectin have been associated with the development of atherosclerosis and the risk of cerebral infarctions. According to pre‐clinical studies, however, they play a protective role against ischemic brain damage. In this study we analysed the relationship between serum leptin and adiponectin levels and the onset or progression of silent brain infarctions in a population of subjects with mild cognitive impairment (MCI) and Alzheimer’s disease (AD).MethodAll data were extracted from the ADNI database. All patients with available serum leptin and adiponectin levels at baseline were selected. Demographic and anamnestic data, neuropsychological test results, tau, phosphotau and amyloid levels in CSF and regional brain metabolism with FDG‐PET data were also extracted. The determination of the number of silent cerebral infarctions was performed on baseline brain MRI. The final population includes 566 subjects, with 58 normal controls, 396 MCI and 112 AD.ResultLeptin levels were significantly lower in patients with MCI than controls at baseline, while adiponectin levels were not different between the three groups. Multivariate regression analysis in patients with cognitive impairment (MCI + AD, 508 subjects) showed that leptin levels were significantly associated with BMI, arterial hypertension and female sex. By stratifying the three diagnostic groups by the presence or absence of baseline infarctions, leptin levels were significantly higher in patients with AD and brain infarcts than in patients with AD without brain infarcts. However, multivariate logistic regression analysis at baseline for the presence or absence of brain infarcts did not confirm the predictive value of leptin. Multivariate longitudinal analysis did not attribute predictive value to serum leptin levels on the development of silent brain infarcts in this MCI and AD population.ConclusionThe evidence on the pathogenetic or protective role of adipokines on ischemic brain damage in the literature is mixed. In this population affected by MCI and AD, serum leptin and adiponectin levels are not associated with the development of brain infarctions; therefore, these results do not support the use of adipokines as biomarkers of cerebrovascular pathology in this population.
Risk prediction of Alzheimer’s dementia in mild cognitive impairment – Impact of AD biomarker disclosure on quality of life, mental health and risk knowledge: The PreDADQoL study
Authors: Rostamzadeh Ayda , Schwegler Carolin , Rosende‐Roca Maitee , Moreno Mariola , Canabate Pilar , Ortega Gemma , Schmitz‐Luhn Björn , Boada Mercè , Woopen Christiane , Jessen Frank 
Published: June 2023

AbstractBackgroundExpanded technologies in early AD detection have led to an increasing number of individuals with mild cognitive impairment (MCI) asking for biomarker‐based risk prediction of Alzheimer’s dementia. However, standardized approaches for counseling and disclosure of individuals with MCI are lacking in clinical practice. First studies on cognitively healthy individuals and MCI patients have reported no major impact on psychological wellbeing after AD biomarker disclosure, but data on quality of life, health behavior changes and risk knowledge of individuals with MCI before and after AD biomarker disclosure is sparse.MethodThe transnational (Germany and Spain) project PreDADQoL recruited a total of 76 MCI patients and caregivers. Dyads received a standardized counseling on predictive biomarker‐based diagnosis of AD. MCI patients consenting to cerebrospinal fluid (CSF)‐biomarker testing received a standardized disclosure of their biomarker status and consecutive dementia risk. Following a mixed‐methods approach the empirical part of the project conducted follow‐up visits over 3 months to assess the effects of predictive AD diagnosis on various outcomes.ResultCounseling on biomarker‐based AD detection and disclosure of dementia risk has no major impact on mental health and quality of life on MCI patients and their caregivers on short term follow‐up. Although the counseling included recommendations on lifestyle modification, individuals with MCI and caregivers reported a significantly less beneficial lifestyle 3 months after risk disclosure as compared to baseline. Despite adequate numeracy skills, the dementia risk perception in individuals with MCI did not correlate with the communicated risk, whereas caregivers’ risk perception correlated significantly with the communicated risk.ConclusionOur findings confirm that predictive AD diagnosis causes no major harm with regard to mental health and quality of life. However, despite the psychoeducational approach during the counseling and disclosure sessions with facilitating supplies, such as visual aids and take‐home material, the anticipated fostering effects on health behavior and risk knowledge remain modest. Our study contributes to the extended understanding of individuals with MCI and their caregivers when facing early AD detection. The PreDADQoL study will synergize empirical data with ethical and legal considerations for a guidance of good clinical practice in the field of predictive AD diagnosis.
Depression in older patients with dementia during COVID‐19 pandemics in Romania ‐ a geriatric center perspective
Authors: Oprea Violeta Diana , Sârbu Fabiola , Romila Aurelia 
Published: June 2023

AbstractBackgroundA convincing body of evidence identifies depression as a risk factor for later life dementia, whereas later life depression should be considered as a prodrome for dementia. COVID‐19 pandemics highly affected elderly, and those suffering from dementia were among the most vulnerable populations to a severe evolution of SARS‐CoV2 infection as well as impacted by social isolation.MethodWe analyzed the association of depression in a study group of 162 geriatric patients, admitted due to complains of neurocognitive and psychiatric symptoms but also to other comorbidities, hospitalized in 2020‐2021 in our Geriatric Clinic after the pandemic was declared. All patients were evaluated using standard Mini Mental State Evaluation (MMSE) scale, Clock‐ Drawing Test (CDT) and Geriatric Depression Scale (GDS). Native cerebral CT‐scan imaging was used to assess if any neurobiological changes occurred.ResultThe incidence of dementia was 72.8% in the study group of 162 consecutive hospital admissions in the geriatric department. Out of the 118 cognitively impaired patients (out of which 9 were previously diagnosed with Alzheimer Disease), 73.7% had associated depression; other prevalent comorbidities in the geriatric lot were cardiovascular, neurologic, metabolic and musculoskeletal disorders. The relative risk of depression associated to dementia was 1.75. The complex relationship linking dementia and depression has also neuropathological underlying mechanisms‐ decreased cortical thickness and white matter loss were associated with both depressive symptoms and impairment of cognitive functions. In our study the majority of the patients (62.3%) presented structural abnormalities of different categories in cerebral CT‐scan imaging.ConclusionThis high incidence reported on the association between dementia and depression in geriatric hospitalized patients is in line with the results of other studies, supporting the idea of standardizing a clinical assessment protocol for evaluating both cognitive dysfunction and depression in all elderly patients and monitoring their evolution. COVID‐19 conditions isolating elderly and restricting their access to medical services increased the risk of worsening their cognitive status and mental health. As the effective treatments for dementia remain scarce, clinicians could use a preventive approach by identification of high‐risk individuals ‐ one of the most relevant dementia risk factors being depression.
Olfaction and anxiety differently associated in men and women in cognitive physiological and pathological aging
Authors: Cieri Filippo , Zhuang Xiaowei , Ritter Aaron , Caldwell Jessica ZK 
Published: June 2023

AbstractBackgroundOlfactory and affective factors are associated in a complex way, likely due to partial overlap in brain regions involved. Although the role of olfaction in disorders such as Parkinson Disease (PD) is documented, less clear is the association between olfaction and psychological symptoms, such as anxiety, in Mild Cognitive Impairment (MCI) and elderly cognitively healthy controls (HCs). Also, the role of sex differences in olfaction and psychological symptoms in healthy and pathological aging is poorly understood.MethodsWe included 117 subjects: 29 HCs (62.1% women), 43 MCI (34.9% women) and 45 PD (40% women), from the Center for Neurodegeneration and Translational Neuroscience. We assessed olfactory function with the Brief Smell Identification Test (BSIT) and anxiety with the State Trait Anxiety Inventory (STAI). We used a regression model for BSIT predicting STAI_Traits. We also used an interaction regression model to determine interaction between sex and olfaction predicting anxiety traits, in our three different groups.ResultsLoss of olfaction is related to greater anxiety traits in all our groups. Our regression model for BSIT predicting STAI_Traits is significant in HCs: p = 0.015; MCI: p = 0.001 and PD: p = 0.038 (adjusted for age, gender and education). Our interaction model olfaction*sex interaction to explore sex difference in the effect of olfaction on anxiety traits, showing that in HCs, for every unit increase in BSIT, trait anxiety decreased by 7.63 in men (p = 0.009) and 1.5 in women (p = 0.225); in MCI, for every unit increase in BSIT, trait anxiety decreased by 1.19 in men (p = 0.048) and 3.03 in women (p = 0.0036); in PD, for every unit increase in BSIT, trait anxiety decreased by 1.73 in men (p = 0.004) and 0.41 in women (p = 0.3632).ConclusionsOlfaction and anxiety are correlated in physiological and pathological aging, but differently in men and women. We show a closer relationship in men compared to women. In HC and PD olfaction is more closely and significantly correlated in men compared to women. In MCI we note an opposite pattern, with women show a slightly closer link between anxiety and olfaction.
Impact of disease stage and reference region selection on longitudinal tau 18F‐MK6240 PET in Alzheimer’s disease
Authors: Krishnadas Natasha , Dore Vincent , Robertson Joanne , Ward Larry , Fowler Christopher J , Masters Colin L. , Bourgeat Pierrick , Fripp Jurgen , Villemagne Victor L. , Rowe Christopher C. 
Published: June 2023

AbstractBackgroundTau PET imaging enables prospective longitudinal observation of the rate and location of tau accumulation in Alzheimer’s disease (AD). 18F‐MK6240 is a newer, high affinity tracer for the paired helical filaments of tau in AD. It is widely used in clinical trials, despite sparse longitudinal natural history data. We aimed to evaluate the impact of two reference regions on the magnitude and effect size of regional change.MethodOne hundred and fifty‐eight participants: 83 Aβ‐ cognitively unimpaired (CU), 37 Aβ+ CU, 19 Aβ+ MCI, 19 Aβ+ AD had annual 18F‐MK6240 PET imaging for a mean of 1.6 years. Standardized uptake value ratios (SUVR) were generated for three in‐house composite ROI: mesial temporal (Me), temporoparietal (Te), and rest of neocortex (R), and a Free‐Surfer derived meta‐temporal (MT) ROI. Two reference regions were examined: cerebellar cortex (SUVRcb) and eroded subcortical white matter (SUVRwm).ResultFigure 1 shows the annual rate of tau SUVR change in composite ROI. In Aβ+ CU, tau accumulation was greatest in Me (2.8‐3.2%/ year) (vs Aβ‐ CU, Cohen’s d = 0.30 SUVRcb, 0.24 SUVRwm) and MT (3.2‐3.6%/year) (vs Aβ‐ CU, d = 0.36 SUVRcb, 0.31 SUVRwm). In Aβ+ MCI, tau accumulation was greatest in Te (2.3‐3.7%/year) (vs Aβ‐ CU, d = 0.34 SUVRcb, 0.41 SUVRwm). In Aβ+ AD, greatest increase was in Te and R, with a decrease in Me. In Aβ+ AD, SUVRcb showed marginally greater increase in these regions (e.g. 3.8%/year compared to 2.68%/year SUVRwm in R) (vs Aβ‐ CU, d = 0.60 SUVRcb, 0.27 SUVRwm). In the young Aβ+ AD dementia group, spill‐over from adjacent high cortical binding or an increase in white matter binding elevates signal in the reference region.ConclusionThe rate of tau accumulation varies according to brain region and baseline tau. Change is greatest in the MTL in preclinical AD, in the MTL and lateral temporal cortex in MCI, and Braak V‐VI regions in AD dementia. The PET measured change is greater and less variable using an eroded white matter reference region, except in AD dementia, where spill‐over from adjacent high cortical binding or increase in white matter binding elevates the reference region.
Medial temporal lobe (MTL) – default‐mode network (DMN) functional connectivity disruption in the early stages of the progression of Alzheimer’s disease in a multimodal ADNI3 MP‐RAGE and EPI‐BOLD Basic cohort
Authors: Grajski Kamil A 
Published: June 2023

AbstractBackgroundA cross‐sectional same‐session multi‐modal analysis (T1, rsfMRI) was applied to identify potential biomarkers of the progression from cognitively normal (CN) to significant memory concern (SMC) and early and late mild cognitive impairment (EMCI, LMCI) in Alzheimer’s disease.MethodsAn ADNI3 EPI‐BOLD Basic sub‐population (N = 133) with baseline diagnosis CN (N = 45), SMC (N = 46), EMCI (N = 22), and LMCI (N = 20), matched for age (p = 0.61), education (p = 0.26), gender (p = 0.26), morphometric (FreeSurfer 7), and fMRI (AFNI) measurements, was processed with a hybrid a priori data‐driven method that identified anchor‐target ROI pairs in rsfMRI [1]. ROI pairwise correlations were False Detection Rate (FDR) corrected in a parallel group‐level one‐way four‐factor (CN, SMC, EMCI, LMCI) ANOVA and post hoc pairwise t tests were performed for significant tests only.ResultsA 3‐mm grid of ROI (r = 6mm) seeds in left MTL yielded 488 ROI “anchors”. 3D (Fisher Z‐transformed) correlation maps were computed for each subject for each anchor ROI and input to a group‐level one‐way four‐factor 3D ANOVA. Cluster analysis (Nvox = 20; p = 0.02; P = 3.45) of the 3D F statistic maps yielded 1,774 target ROIs. An r = 6mm ROI was placed at the center of mass of each target cluster. ROI anchor‐target pair correlations were input to a group‐level one‐way four‐factor ANOVA FDR corrected (q = 0.005; p* = 0.0035, permutation, N = 1000) which identified 1,179 significant tests. Post hoc pairwise t tests only on the significant ANOVA tests were FDR‐corrected (q = 0.005) and yielded 163 significant SMC‐CN tests (p* = 6.8×10−4); 158 EMCI‐CN tests (p* = 6.6×10−4); and 120 LMCI‐CN tests (p* = 5.1×10−4). The significant target ROI masks were summed which identified 35‐44 clusters. The same hybrid a priori data‐driven method was then applied in independent runs using as anchor regions the left amygdala, thalamus, substantia nigra, and accumbens area. The resultant spatial distribution of significant target ROI masks predominantly, but not uniformly coincided with DMN‐associated regions. An independent analysis of right hemisphere yielded similar results.ConclusionsA hybrid a priori data‐driven approach applied to anchor ROIs in MTL and multiple subcortical regions identified target ROIs that were predominantly, but not uniformly associated with DMN.[1] Grajski, K. A., Bressler, S., and ADNI. (2019). Neuroimage Clin. 2019;23:101860.