bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of cannabidiol (CBD) treatment in a mouse model of Alzheimer’s disease through regulation of Interleukin‐5
Authors: Khodadadi Hesam , Salles Évila Lopes , Jarrahi Abbas , Khan MB , Yu Jack C , Morgan John C. , Hess David C , Seyyedi Mohammad , Vaibhav Kumar , Dhandapani Krishnan M , Baban Babak 
Published: December 2021

AbstractBackgroundWith the rising prevalence as the main cause of dementia, Alzheimer’s disease (AD) is emerging as one of the most important medical and social challenges for the healthcare system in both developed and developing countries. Despite significant advancement in our understanding of AD and improvement in therapeutic modalities for AD patients, however, there is currently a marked lack of definitive and effective treatment for AD. Therefore, there is an exigent need for an alternative therapy to treat the underlying causes of AD rather than its symptomatic effects. Cannabidiol (CBD) is a safe, non‐psychoactive phytocannabinoid produced by cannabis plant. Increasing evidence from our laboratory and others suggests an immunomodulatory role for CBD in a variety of inflammatory conditions, potentially including neurodegenerative diseases such as AD. Recent evidence and studies have challenged the traditional view about the role of immune system in the pathogenesis of neuroinflammatory diseases specifically AD. There are several studies indicating that Interleukin (IL)‐5, a Th2 type cytokine has the potential to alleviate the symptoms of cognitive decline in AD. Therefore, in this study we are investigating whether CBD can improve the symptoms of AD through activation of IL‐5 signaling.MethodAge matched normal (Wild type, WT) and 5XFAD (Mouse model for familial AD) were used to evaluate their cognitive function and anxiety by using Morris water maze and Open field behavioral tests. All animals were sacrificed, and their meninges, brain and blood were collected for further flowcytometry analysis, immunohistochemistry and immunofluorescence imaging.ResultCBD was able to modulate the level of IL‐5 expression which was associated with improvement in the behavioral and cognitive functions of AD mice.ConclusionOur findings suggest a possible alternative and therapeutic role for CBD in the treatment of AD. Further, these discoveries present evidence to support the beneficial role for IL‐5 as a potential biomarker in the diagnosis and treatment of AD, opening a new horizon for research to find an effective therapeutic modality for AD.
BDNF‐mediated improvements in cognition after computerized cognitive training
Authors: Nicastri Casey M , Simon Sharon Sanz , McFeeley Brittany , Ledreux Aurélie , Håkansson Krister , Granholm Ann‐Charlotte , Mohammed Abdul H. , Daffner Kirk R 
Published: December 2021

AbstractBackgroundEvidence suggests that engagement in cognitively stimulating activities may reduce risk of cognitive deterioration and dementia. Mechanisms underlying these observations remain to be determined. Animal research indicates that brain‐derived neurotrophic factor (BDNF) plays an important role in neural plasticity, neurogenesis, synaptic growth, and cognitive performance. Working under the assumption that augmented BDNF levels benefit brain function, investigations of human subjects have focused on determining whether physical or mental activities can increase BDNF levels. Surprisingly little research has been devoted to linking alterations in BDNF to changes in cognition. This study aimed to determine whether changes in BDNF contribute to the enhancement of cognitive performance after computerized cognitive training (CCT). We have demonstrated that five weeks of CCT emphasizing working memory (WM) was associated with improvement on an untrained test of WM/processing speed, the Digit Symbol Test. Here, we investigated whether this improvement was mediated by changes in BDNF levels.MethodSeventy‐five older adults, ages 65‐86, at two sites (USA and Sweden) were randomized to either Cogmed Adaptive (n=37) or Non‐Adaptive (active control) (n=38) CCT. Under the adaptive CCT, task difficulty was revised on a trial‐by‐trial basis to create a consistently high level of challenge. Under the active control condition, task load remained at a constant, relatively low level. CCT was performed in the homes of participants, five days per week, over five weeks. Serum BDNF levels and performance on Digit Symbol were measured pre‐ and post‐intervention.ResultAnalysis using linear mixed models demonstrated an interaction between time and intervention group for Digit Symbol score (p=.036) and BDNF level (p=.013) Only the adaptive CCT group demonstrated an augmentation of BDNF level (p=.014) and improvement in Digit Symbol scores (p<.001) after training. Mediation analysis revealed that changes in BDNF level accounted for the intervention‐related improvement in performance on Digit Symbol. Regression analysis indicated that changes in BDNF level predicted changes in Digit Symbol score (p=.010).ConclusionThe results of this investigation suggest that increases in BDNF linked to cognitive training mediate improvement in cognitive performance. Additional research is needed to determine if these findings are specific to WM or are observed in other cognitive domains.
What do data‐driven Alzheimer’s disease subtypes tell us about white matter pathology and clinical progression?
Authors: Chen Hanyi , de Silva Eric , Sudre Carole H , Barnes Jo , Young Alexandra L. , Oxtoby Neil P. , Barkhof Frederik , Alexander Daniel C. , Altmann Andre 
Published: December 2021

AbstractBackgroundThe progression of Alzheimer’s Disease (AD) is heterogeneous with different brain regions manifesting pathology at different times during the disease. Differential sequences of grey matter (GM) volume changes, defining imaging‐based subtypes, may represent alternative disease origins, pathways or severity. Additionally, volumes of white matter hyperintensities (WMH), which increase with age, are associated with AD. In this study we used a machine learning method to estimate three types of AD trajectories and assessed their WMH load and longitudinal prognosis.MethodSubtype and Stage Inference (SuStaIn; Young et al., https://doi.org/10.1038/s41467‐018‐05892‐0) was used to estimate data‐driven disease progresion subtypes from cross‐sectional GM volumes in 795 subjects (from ADNI1/GO/2 with baseline 3T MRI scans processed with FreeSurfer 5.1 passing data quality control). Following additional quality control WMH volumes for 575 of these ADNI subjects were calculated using a Bayesian Model Selection method BaMoS (Sudre et al., https://doi.org/10.1109/TMI.2015.2419072) from three diagnostic groups: Healthy Controls (HC; n=181), Mild Cognitive Impairment (MCI; n=310) and Alzheimer’s Disease (AD; n=85). The association between SuStaIn subtypes and WMH and diagnostic conversion rates were evaluated using multiple pairwise comparisons and survival analysis, respectively.ResultSuStaIn identified three subtypes with distinct atrophy patterns: typical (atrophy begins in hippocampus and amygdala), cortical (atrophy starts in the temporal lobe, followed by cingulate and insula) and subcortical (atrophy begins in pallidum, putamen and caudate) (Figure 1). Participants with the subcortical subtype exhibited a significantly slower rate of clinical progression to MCI or AD (Figure 2, Table 1). Furthemore, subjects with the subcortical subtype showed lower median WMH (Figure 3a), a pattern observed across the diagnostic groups (Figure 3b).ConclusionParticipants classified as the subcortical subtype were least likely to have white matter structural changes associated with neurodegeneration and displayed the slowest rate of clinical conversion. While late hippocampal involvement in the subcortical subtype may explain less severe clinical symptoms and slower disease progression, the reason for lower WMH associated with this subtype trajectory is unknown. Further studies are needed to investigate the link between WMH and AD atrophy subtypes.
Impact of socio‐demographic features and lifestyle in cognitive performance of Peruvian adults
Authors: Vilca Brenda Chino , Zegarra‐Valdivia Jonathan Adrian , de Frutos Jaisalmer 
Published: December 2021

AbstractBackgroundThe related‐age changes are associated with a continuous process of cognitive decline. In normal aging, only 1‐2% of the population develop dementia compared with 10 to 15 % with previous mild cognitive impairment. In this line, diverse characteristics exist that act as protective factors front the disease onset and are related to better cognitive performance in the population. Our knowledge about these features can be the first step to combat dementia and reduces the impact on the elderly quality of life. The present study aimed to investigate sociodemographic characteristics and lifestyle factors affecting the cognitive function in Peruvian adults.Method1499 subjects (aged from 42 to 98) participated in the Interview Survey in Health Services of Primary Attention in Arequipa (Perú). The cognitive performance was evaluated with the Addenbrooke's Cognitive Examination ‐ Revised (ACE‐R). The χ2 test and multiple logistic regression models were used to define the association between cognitive impairment and socio‐demography and lifestyle variables.ResultThe multivariate analysis indicated that age, sex, single, more years of education, living in the urban area, practicing physical activities, and reading were associated with a lower risk of cognitive impairment.ConclusionRisk factors associated with dementia are even more visible in Latin America Countries (LAC). The wide variability in the sociodemographic characteristics and access to health care services limit early detection of the disease. The lifestyle changes could help prevent or decrease the risk of cognitive impairment and reduce the disease's impact on vulnerable environments.
Associations between neighborhood greenspaces and cognitive and brain volume measures in cognitively normal older adults
Authors: Besser Lilah M , Chang Lun‐Ching , Mitsova Diana , Renne John , Carmichael Owen T , Moulder Krista L , Morris John C , Galvin James E 
Published: December 2021

AbstractBackgroundLiving in neighborhoods with greater vegetation and park space has been associated with better brain health in older adults. While mechanisms relating greenspaces and brain health are not well understood, greenspaces may lead to better cognition and lower Alzheimer’s risk by providing social and physical activity opportunities and stress reduction, factors previously associated with Alzheimer’s disease. This study investigated associations between neighborhood greenspace types and multiple brain health measures for Alzheimer’s disease and related disorders, which has been examined little to date.MethodResidential addresses and magnetic resonance imaging (MRI) volumes were obtained from cognitively‐normal participants who completed Uniform Data Set assessments from Knight Alzheimer’s Disease Research Center (St. Louis, Missouri). Addresses geocoded to US Census tracts were linked to National Land Cover Dataset data to identify open spaces and areas with tree canopy (hereafter termed forest). Longitudinal clinical data were obtained from the National Alzheimer’s Coordinating Center. Outcomes included CDR® Sum of Boxes, four cognitive domain z‐scores (memory, attention, executive function, and language) constructed from ten neuropsychological tests, and hippocampal and white matter hypointensity volumes (167 had T1‐weighted MRI). Multi‐level linear regression models (clustering on Census tract and participant) controlled for demographics, comorbidities, and neighborhood disadvantage and population density. Brain volume models additionally controlled for intracranial volume.ResultParticipants (n=553) were on average 74 years old (standard deviation [SD]=7), 16% were Black, and 81% were White. Neighborhood percentage of open space ranged from 0 to 42% (mean=6.6%, SD=9.9) and forest ranged from 0‐16% (mean=0.2%, SD=1.4). Greater percentage of forest was associated with lower baseline episodic memory (estimate=‐0.79; 95% confidence interval [CI]=‐1.13, ‐0.46), slower annual episodic memory declines (estimate=0.069, 95% CI=0.002, 0.137), higher baseline executive function (0.15, 95% CI=0.03, 0.26), and fewer white matter hypointensities (estimate=‐3,521 mm3, 95% CI=‐6,443, ‐600). No other associations were observed.ConclusionLiving in neighborhoods with more tree canopy was associated with lower episodic memory but higher executive function at baseline, slower annual declines in executive function, and fewer white matter hypointensities. This study suggests mixed associations between neighborhood tree canopy and brain health that will need to be replicated in larger, diverse cohorts.
Cognitive performance predictors of incident motoric cognitive risk syndrome
Authors: Ayers Emmeline , Verghese Joe 
Published: December 2021

AbstractBackgroundMotoric cognitive risk syndrome (MCR) is a gait based pre‐dementia syndrome that builds on operational definitions of mild cognitive impairment (MCI), and is associated with increased risk for Alzheimer’s Disease and other types of dementia. Declines in cognitive function associated with risk of developing MCR have not been established. We aimed to examine the association between cognitive performance on tests of memory and executive function (EF) and related processes and risk of incident MCR.MethodOf the 541 non‐demented participants (aged 65+) in a community‐based cohort, at baseline 22 met criteria for MCR, 58 for MCI, and 17 met criteria for both MCR and MCI, and were excluded from the analyses. Cognitive performance was measured using seven tests: the free recall score from the Free and Cued Selective Reminding Test, Figure Recall from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Story Recall from the RBANS, Category Fluency, Controlled Oral Word Association Test, Digit Symbol Substitution test and Trail Making Test part B. A confirmatory factor analysis indicated that these cognitive tests fell into two categories of cognitive function: memory and EF and related processes. Cox proportional hazard models adjusted for age, sex and education was used to examine the association between cognitive test performance and incident MCR in 444 participants. For the purpose of comparison, we also examined the association between cognitive performance and MCI.ResultOver a mean follow‐up of 3.0 years, 37 participants developed incident MCR and 69 incident MCI. Performance on tests of EF and related processes was associated with risk for MCR (adjusted hazard ratios (aHR) ranging from 0.96 to 0.99). One memory test (free recall) was associated with risk of MCR (aHR: 0.94, 95% Confidence Interval: 0.89‐0.99). Performance on all tests of memory (aHR ranging from 0.81 to 0.92) and EF and related processes (HR ranging from 0.94 to 0.99) was associated with increased risk of MCI.ConclusionCognitive performance on tests of EF and related processes are associated with increased risk of MCR. This may be indicative of a distinct underlying pathology in patients who are at risk of MCR.
Impact of brisk walking on cognitive decline in adults with and without early impairment: A FLAME analysis in the PROTECT cohort
Authors: Brooker Helen , Hayman Vincent , Aarsland Dag , Creese Byron , Ballard Clive , Corbett Anne 
Published: December 2021

AbstractBackgroundEvidence continues to build to support the value of regular physical exercise as an affordable dementia risk reduction intervention for cognitively healthy older adults. However, the types and intensities of exercise that yield the greatest benefits are yet to be established. This study uses the recently published FLAME cognitive analysis measure to explore the impact of exercise on cognition in older adults in an online cohort.MethodPROTECT is an innovative online study (www.protect.org.uk) in adults aged 50 and over in the UK, Participants complete annual cognitive assessment in addition to lifestyle and health measures. Participants were divided into three cohorts (Normal Cognition, Stage 2 Early AD and Stage 3 Early AD – based on the FDA framework) using baseline data from the cognitive assessment battery. Participants (n=8079) in these groups who completed the exercise questionnaire on two consecutive timepoints and within two weeks of cognitive assessment were included in this analysis. The analysis compared change in cognition from baseline using a one‐way ANOVA with physical activity type as a fixed factor and gender, age and education fitted as covariates.ResultComposite measures of Speed of Attention [p=0.0003, d=0.26], Accuracy of Attention [p=0.0008, d=0.21], Memory [p=0.0017, d=0.11] and Executive Function [p=0.0006, d=0.09], as well as the composite FLAME measure [p=0.006, d=0.24] all showed significant benefits in participants with Normal Cognition who performed brisk walking at least twice a week, compared to indiviudals with lower levels of exercise. These benefits were also evident in participants In the stage 2 and 3 Early AD groups [Stage 2: FLAME p=0.003, d=0.13; Stage 3: FLAME p=0.006, d=0.19].ConclusionThese findings contribute further evidence that regular participation in exercise of at least moderate intensity offers benefit to major aspects of cognitive function in both healthy aging individuals and those at the pre‐clinical stages of cognitive decline.
Spontaneous blinking and brain health: Can blink‐related oscillations capture brain changes in aging?
Authors: Liu Careesa C. , Meltzer Jed A. , Keerthi Prerana , Pappas Chloe , Sekuler Allison B. ,   Cambridge Centre for Aging and Neuroscience (Cam‐CAN)
Published: December 2021

AbstractBackgroundBlink‐related oscillations (BROs) are recently discovered neurophysiological responses that follow spontaneous blinking, and represent environmental monitoring and awareness processes as the brain evaluates new visual information after eye reopening. BROs strongly activate the precuneus which is one of the earliest brain regions impacted by Alzheimer’s disease (AD) neuropathology, and as such may provide an important avenue for assessing and monitoring brain health in aging. In this study, we conducted the first investigation of BRO effects in normal aging to determine whether these responses can capture aging‐related brain changes.MethodThis research used data from the Cambridge Centre for Aging and Neuroscience (Cam‐CAN) repository, which comprises magnetocenphalography (MEG) and structural magnetic resonance imaging (MRI) from 700 healthy adults aged 18‐88. The MEG paradigm consists of a target detection task with simultaneous auditory and visual stimulation. MEG data were first denoised using independent component analysis, then BRO responses were derived by segmenting the cleaned data into 3s epochs time‐locked to spontaneous blinking. Participants were divided into 4 age groups comprising the youngest (18‐30), middle‐young (31‐50), middle‐old (51‐70), and oldest (71‐90), and analyses were performed using global field power (GFP) and minimum norm estimates to examine BRO effects at the sensor‐ and source‐levels, respectively.ResultResults showed that BRO responses were present in all age groups. GFP amplitude increased with age during intervals spanning post‐blink BRO peaks, but not the pre‐blink baseline (p<0.05). BROs also activated brain regions spanning the occipital, temporal, and parietal cortices in all age groups (p<0.05 FWE), with the extent of activation increasing with age. Moreover, the activation extent of precuneus and hippocampus regions showed inverted U‐shape with age, increasing towards the middle‐old group but decreasing in the oldest.ConclusionThese results demonstrate for the first time that BRO responses can capture brain changes in normal aging, with increased neural activation for processing blink‐related information as one ages. Results suggest that BROs may represent a simple yet powerful avenue for measuring aging‐related brain function changes, providing a potential tool for early detection of neurodegeneration – particularly with respect to the precuneus and hippocampus regions highly implicated in AD.
Comparison between face‐to‐face and remote language assessment with the Minilinguistic State Examination
Authors: Pistolesi María Agustina , Martínez‐Cuitiño Macarena , Vivas Leticia , Manoiloff Laura , Paolantonio Patricia , Fernández‐Zaionz Axel , Ortells Tobias , Geraldine Reimundo , Montero Lucía , Nieto Mayda , Romero Nicolás , Castaño Federico , Sanchez María Victoria 
Published: December 2021

AbstractBackgroundThe COVID‐19 pandemic had an impact on neuropsychological assessment and implied an adjustment in the settings of evaluation. To continue providing clinical assistance to patients, it was necessary to adapt previously developed tools for face‐to‐face evaluation for a remote format. To know the effectiveness of this way of administration, it becomes necessary to identify whether this new modality differs significantly from the face‐to‐face one. With the pandemia some researcher started to make this comparisons. Identify these possible differences using short tools makes it easy to access this information. The Minilinguistic State Examination (MLSE) is a recently developed tool for assessing acquired language difficulties that is being adapted and validated in various languages.Objective: The aim of this work is to identify possible differences in the performance of control subjects by comparing the face‐to‐face and remote clinical evaluation using the MLSE Argentinean version.MethodTwo groups of healthy subjects were assessed: 23 face‐to‐face and 31 remotely. All were native Spanish speakers with middle to high educational level. A Mann‐Whitney´s U test was performed between groups comparing the scores on each of the subtests of the MLSE (except sentence repetition because it was subtly changed for the remote version).ResultThere were no significant differences in any of the aforementioned tasks concerning both modalities (p > .005) but only in the comprehension part of repeat and point (U = 310; p = .004), where better performance was observed for the remote group. Additionally, within modality (face‐to‐face and remote), comparisons were performed considering age and educational level and there were no statistically significant differences (p > .005).ConclusionThe remote modality of this version of the MLSE could be a good option to perform a language screening. The better performance observed in the remote group in one comprehension task could be explained by the higher cultural level of that group. That can be a bias when considering samples that access computer mediated evaluations. Thus, additional sample must be collected including lower educated participants. Also, further studies are necessary to assess the utility of the remote modality for patients with aphasia.