bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shorter disease duration in females with sporadic frontotemporal dementia
Authors: de Boer Sterre C.M. , Riedl Lina , Van der lee Sven J , Otto Markus , Anderl‐Straub Sarah , Landin‐Romero Ramon , Sorrentino Federica , Fieldhouse Jay L.P. , Reus Lianne M. , Halliday Glenda M , Galimberti Daniela , Diehl‐Schmid Janine , Ducharme Simon , Piguet Olivier , Pijnenburg Yolande A.L. 
Published: December 2022

AbstractBackgroundPrevious reported sex differences on disease duration (DD) of frontotemporal dementia (FTD) have been inconsistent and lack the comparison between genetic and sporadic FTD. Our aim was to study the difference in disease duration between males and females in genetic and sporadic FTD.MethodMortality data was obtained from 61 deceased patients with genetic FTD (52% male) and 117 deceased patients with sporadic FTD (64% male) from the international FTD cohort previously reported by de Boer et al., 2021. The age at symptom onset (AAO), age at death (AAD) and the DD (defined as the time between age at symptom onset and age at death) were compared between males and females in the genetic and sporadic FTD group using Mann Whitney U tests.ResultGenetic FTD did not show significant sex differences in AAO, AAD and DD (p = 0.3, p = 0.3, p = 0.8 respectively, Figure 1). In sporadic FTD, the AAO and AAD did not significantly differ between males and females (p = 0.8 and p = 0.2 respectively). The DD in the sporadic FTD group was significantly shorter in females (median DD 7.0 years) in comparison to males (median DD 8.0 years, p = 0.01, Figure 2).ConclusionIn this study we show that females with sporadic FTD have a shorter disease duration than males whereas in genetic FTD the disease duration does not differ between sex. These findings suggest the existence of sex‐related differences in the disease course of sporadic FTD. We urge the need for international epidemiological FTD studies to further explore the role of sex in both genetic and sporadic FTD.
Cortical diffusivity associates with early neuronal damage
Authors: Nowell Joseph , Debatisse Justine , Femminella Grazia Daniela , Raza Sanara , Edison Paul 
Published: December 2022

AbstractBackgroundDiffusion weighted imaging can provide a marker a microstructural damage which cannot be detected by conventional structural MRI. Changes in cortical diffusivity may be a value marker of neuronal breakdown, which predates macrostructural damage. We aimed to evaluate the efficacy of cortical diffusivity in predicting the extent of metabolic changes in different stages of Alzheimer’s disease progression.Method90 participants diagnosed with mild to moderate Alzheimer’s disease were recruited at Imperial College London. A median split was conducted to categorise participants into ‘Early’ (MMSE ≥ 25, n = 42) and ‘Late’ stage of AD groups (MMSE < 25, n = 48) to reflect different stages of disease progression. All participants underwent [18F]fluorodeoxyglucose imaging with arterial input, t1‐weighted MRI images and diffusion weighted images were also acquired. Spectral analysis was conducted to calculate the cerebral metabolic rate of glucose (CMRglc). CMRglc and mean diffusivity maps were spatially normalised to MNI space and individualised grey matter object maps were created for all participants. Linear regression was conducted between CMRglc and mean diffusivity maps. Mean diffusivity and CMRglc values within the temporal lobe were extracted to confirm voxelwise results.ResultIn this cohort, voxel‐wise statistics revealed a significant relationship between cortical diffusivity and reduced CMRglc, particularly in our ‘early’ stage AD group. Most notable correlations were located within temporal lobe regions. Regional analysis revealed that increased temporal lobe mean diffusivity was strongly correlated with decreased CMRglc in ‘early’ AD participants (r=‐0.525, p<0.001, 95% CI: ‐0.263 to ‐0.715). We found evidence of a weaker correlation in the ‘late’ AD group between increased diffusivity and CMRglc reductions within the temporal lobe (r=‐0.322, p=0.026, 95% CI: ‐0.042 to ‐0.555).ConclusionCortical mean diffusivity is a valuable predictor of early neuronal damage measured by cerebral glucose metabolism in Alzheimer’s disease. This association was strongest in earlier stages of the disease trajectory, as such, we establish that cortical mean diffusivity as an early biomarker in Alzheimer’s disease which reflects early changes in tissue integrity and cell/organelle breakdown.
TSPO gene polymorphism in Korean population
Authors: Shin Dong Jin , Noh Young 
Published: December 2022

AbstractBackground18‐kDA translocator protein (TSPO protein) expression increases in neuroinflammation. Specific ligands that binds to TSPO protein can be used to visualize neuroinflammation. Due to the reported dependency of binding properties of the second‐generation TSPO ligands on a genetic polymorphism of the TSPO gene, all individuals were genotyped and classified as low‐, medium‐, or high‐affinity binder (LAB, MAB, and HAB). The objective of this study is to investigate the rs6971 gene polymorphism in Korean population.MethodWe performed genetic testing in 109 subjects including Alzheimer’s disease, mild cognitive decline, Lewy body disease, subcortical vascular dementia, and cognitively unimpaired participants. All of them performed MRI and detailed neuropsychological test. 29 participants also took 18F‐DPA714 PET. Exon 4 of the TSPO gene containing the polymorphism rs6971 (Ala or Thr at position 147) as well as exon/intron junctions were PCR amplified and sequenced using Sanger method. The identified rs6971 genotypes (C/C, C/T, or T/T) code for the amino acids Ala/ Ala, Ala/Thr, or Thr/Thr at position 147 of the TSPO protein and were considered to generate a high‐, medium‐, or low‐affinity binding phenotype, respectively.ResultWe found 96.3% of the study subjects were HAB (105 out of 109 subjects), and 3.7% of the subjects were MAB (4 out of 109 subjects). There was no participant who was LAB. From HapMap data allele frequency, American group had 69.2%of HABs, 28% of MABs, and 2.8% of LABs. In African group, 67.4% was HABs, 29.4% was MABs, and 3.2% was LABs. In Asian group, 96.9% was HABs, 6.1% was MABs, and 0.1% was LABs. In Europe group, 45.7% was HABs, 43.8% was MABs, and 10.5% was LABs.ConclusionKorean population had lesser frequency of MABs and LABs like other Asian population. Therefore, availability of second‐generation TSPO PET related to rs6971 gene polymorphism would be lesser affected.
Accessibility of Mixed Reality Technologies for people living with dementia
Authors: Desai Shital , Abendschein Robin , Astell Arlene J. 
Published: December 2022

AbstractBackgroundMixed reality technologies (MRTs) are increasingly being explored for use in dementia but there is a lack of information about the accessibility of different types of MRT hardware and software to develop new applications. We examine the accessibility of four MRTs for people living with dementia.MethodPhase 1: Step‐by step analysis of all set‐up, initiation and game play actions was undertaken by one of the research team. Phase 2: Twenty‐two people with dementia (mean MoCA 14, aged 63 to 88 years), tested four MRT technologies and applications: Hololens: Young Conker; Xbox Kinect: Bowling; Osmo: Tangram and iPhone‐X: Stack‐AR. Interaction and game play actions were coded to identify accessibility promoting and inhibiting features from video recordings of their play sessions.ResultAccessibility of the four hardware and software pairings varied considerably, including the cognitive demands to successfully interact with both the technology and the games. People with dementia attempted to use all of the technologies and games and found them more or less accessible in line with the step‐by‐step analysis of the hardware/software pairings.ConclusionThe functionality in MRTs that can successfully prompt people with dementia through games could be extended to completing other daily activities, such as cooking. However, successful use requires careful consideration of the cognitive demands and other accessibility factors made by the hardware and software. The findings can support development of bespoke MRT applications for people living with dementia.
DNA methylation profiling across brain regions in Huntington’s disease.
Authors: Wheildon Greg , Weymouth Luke Stephen , Smith Adam R. , Smith Rebecca G. , Troakes Claire , Al‐Sarraj Safa , Lunnon Katie 
Published: December 2022

AbstractBackgroundHuntington’s disease (HD) is an autosomal dominant condition that occurs due to the expansion of a CAG trinucleotide repeat in the Huntingtin (HTT) gene. The translated HTT protein has an expanded polyglutamine sequence thought to cause deleterious effects. These effects cause severe neurodegeneration in the striatum. In HD there is also clear atrophy in the cerebellum and a reduction in cortical thickness, including in the entorhinal cortex (EC). Epigenome wide association studies (EWAS) of DNA methylation differences in HD have thus far been limited to the cerebral cortex and use older technologies such as the Illumina 450K array. In this study, we performed an EWAS of HD in the striatum, EC and cerebellum, using the Illumina EPIC methylation array to profile 850, 000 sites across the genome.Method120 striatum, EC and cerebellum DNA samples from 22 control and 20 HD subjects were selected and matched for sex, age and post‐mortem interval. The samples were chosen to be as free from co‐existing pathologies as possible. The majority of subjects were represented in each brain region. The DNA was bisulfite converted, randomized and profiled using the EPIC array. The methylation intensities for each sample were subjected to quality control (QC). Following QC, the samples were analyzed in R for differences in methylation between HD and control samples within each brain region, before being subjected to cross‐regional analysis.ResultWe have used linear regression models to identify differentially methylated positions (DMPs) in specific brain regions in HD. We have used regional analyses to identify differentially methylated regions (DMRs) consisting of multiple adjacent DMPs. Finally, downstream analyses have highlighted epigenetically altered pathways in disease.ConclusionThis study builds a clearer picture of DNA methylation profiles in HD in disease relevant brain regions. Future studies should integrate this with other levels of genomic regulation.
Biological, physiological, neurobiological, neurophysiological pathogenesis of Alzheimer’s, dementia, neurodegenerative diseases:
Authors: Mayer Gabriele 
Published: December 2022

AbstractBackgroundHuman beings use all sensory organs in biological/physiological, neurological/functional ways to feed the brain/brain cells with necessary input/impulses of all environment information for the brain. Practical review: Our lifestyle, ‐losing anymore in life emotional our reactions are: fear, stress, panic, aggressive, depressive, affected person withdraws him/herself: forgets daily life structures/real‐world, loses relationships of any kind , falls backwards in development stages.Methoda)physiological system: In body/brain are changes of pathological biochemical/neuobiochemical milieu. The brain cells will not work through less neurotransmitters, the brain cells go down.‐The pathological milieu in brain is through less input functions of sensory organs, without/less consciousness.Resulta)Factual review results are:‐cognitive/perceptions skills dysfunctions,‐abilities wakefulness is less,‐deficiencies/shortcomings disorders, ‐reality misconceptions, ‐daily life relationship loss,‐brain related disorders: ‐"vascular earlier microcirculatory failure in brain, Damage of Brain Cells”, ‐neurodegenerative diseases,‐and metabolisms disorders through: ‐ our lifestyle, ‐unhealthy nutrition, ‐not enough fluid intake,‐occupying all sensory organs. b)physiological system: It’s ‐too little fluid, too little blood speed, ‐oxygen lack, ‐nutrients distribution, detoxification, exchanges in cells are too slow. This leads to slower metabolism. ‐And delay processing of motor output with, –movement/balance disorders, ‐brain cells metabolic disturbances,‐circulatory disorders, ‐focus/concentration difficulties.‐perceptions disorders,‐ incorrectly feelings/movements. Through poor flow blood properties: ‐blood speed reduction, ‐brain circulatory disorders,‐body/brain oxygen lack, ‐harmful toxins and medication reactions can not be controlled in combination mix with alcohol. All calling up:‐pathological/neurobiochemical reactions in the brain and this leads to neurodegenerative diseases. ‐c)practical systemresults‐abilities wakefulness/perceptions of all sensory organs are less.‐ deficiencies/shortcomings disorders, ‐reality misconceptions, ‐relationship loss to daily‐life. System: Molecular in brain: a)‐through neurobiochemical changes, neurotransmitters building themselves are low, leads to brain cells death. b)‐synapses transmissions glutamate failures, molecular reactions are misfolded proteins productions, with pathological neurobiochemical reactions: growth of fibrils, amyloids, blockades other brain cells. Cells death : power of weight, press, speed of brain cell death. Human being is dead. It's a normal wrongful process.ConclusionIn practical work:‐prevent, stop this, ‐follow biological, physiological function to feed your human brain/brain cells. Therapy is “Rediscover Recovery Practical Reference Training”, multidisciplinary work fields. The goal is: affected person status rebuilding, person’s reintegration in family (not as patient),
The AppNL‐F mouse model of Alzheimer’s Disease demonstrates reduced serum Aß42 levels and Aß42/Aß40 ratio, changes that correlate with CSF Aß levels and cerebral Aß42 plaque load
Authors: Andersson Emelie , Schultz Nina , Blennow Kaj , Zetterberg Henrik , Hansson Oskar 
Published: December 2022

AbstractBackgroundRecent development of novel assays has made it possible to reliably measure proteins for diagnosis of Alzheimer’s disease (AD) in blood in addition to cerebrospinal fluid (CSF). Previous studies have shown that blood and CSF Aß40 and Aß42 levels correlate in AD patients, and other studies have demonstrated that a reduced plasma Aß42/Aß40 ratio inversely correlates with amyloid burden in the brain (determined by PET). However, more studies are needed to fully understand how these Aß changes in blood correlate with CSF Aß as well as the cerebral Aß plaque load. In this current study, we aim to investigate these associations by the use of a novel knock‐in mouse model, AppNL‐F.MethodSerum, CSF and brain tissue was collected from 3‐18 months old App NL‐F knock‐in mice. Levels of serum and CSF Aß40 and Aß42 were analyzed using Simoa Technology (Quantrix). Mouse brain sections were immunostained against Aß42 to determine the cerebral Aß42 plaque load.ResultIn serum from our AppNL‐F mouse model, we found increased levels of Aß40, decreased levels of Aß42 as well as a decreased Aß42/Aß40 ratio with increasing age, particularly after 12 months of age, which was similar in time to the changes observed in CSF. These alterations in serum Aß42 levels and Aß42/Aß40 ratio were associated with the increase of cerebral Aß42 plaque load (Rs ‐0.50 and ‐0.51, respectively), which were lower compared to the associations between CSF Aß42 and Aß42/Aß40 ratio with Aß42 plaque load (‐0.71 and ‐0.70, respectively).ConclusionOur results from the AppNL‐F knock‐in model, show that decreased serum Aß42 and Aß42/Aß40 ratio are mirroring both the decreased Aß42 and Aß42/Aß40 ratio in CSF as well as correlate with increasing cerebral Aß plaque load. These findings indicate that Aß changes in serum and CSF in the AppNL‐F mouse model mirror Aß alterations seen in preclinical AD. Furthermore, these results suggest that changes in Aß42 and Aß42/Aß40 ratio occur simultaneously in serum and CSF and well in concurrent with the deposition of Aß in the brain.
The association of multimorbidity and neuropsychological test scores in Canadian cohorts recruited in 1991 and 2015
Authors: Vargas‐González Juan‐Camilo , Hachinski Vladimir , Speechley Mark R. , Daley Mark J. , Were Jason , Sharma Ishor , Stranges Saverio 
Published: December 2022

AbstractBackgroundMultimorbidity is associated with cognitive decline. Little information exists regarding whether the relationship between multimorbidity and cognitive decline has changed over the last few decades.ObjectiveTo compare estimates of the association between multimorbidity (MM) and performance on cognitive tests in two prospective cohorts of Canadian community‐dwelling older adults recruited 24 years apart.MethodWe analyzed the two datasets separately, including participants ≥65 years from both baseline and first follow‐up of the Canadian Study of Health and Aging (CSHA, 1991 – 2001; first follow up in 1996) and the Canadian Longitudinal Study on Aging (CLSA, 2015 – ongoing; first follow up in 2018). We excluded participants with baseline dementia. In both cohorts, we defined MM as two or more conditions from a list of 14. The neuropsychological tests were Animal Naming Test (ANT) and the Rey Auditory Verbal Learning Test (RAVL) for both cohorts. Tests of frontal function were the Digit Symbol Substitution Test (DSST) in the CSHA and the Mental Alternation Task (MAT) in the CLSA. We performed multilevel linear modelling. We controlled for confounders, which were detected using a Directed Acyclic Graph.ResultWe included 497 participants from the CSHA and 9308 from the CLSA. The mean age was 78.0 in the CSHA and 72.0 in the CLSA, and male accounted for 36.4% in the CSHA and 50.2 in the CLSA. Mean MM was 2.1 in both cohorts, with a higher prevalence of MM in women (CSHA 63.9%; CLSA 64.2%) than in men (CSHA 55.8%; CLSA 59.5%). When comparing both cohorts, we found that baseline MM was not associated with changes in the Z‐scores for the ANT (CSHA: 0.16, CI95: ‐0.014 to 0.34; CLSA: ‐0.002, CI95: ‐0.044 to 0.04), RAVL delayed recall (CSHA ‐0.033, CI95: ‐0.23 to 0.16; CLSA: 0.031, IC95: ‐0.013 to 0.074), or DSST in CSHA (0.1, CI95: ‐0.084 to 0.29) / MAT in CLSA (0.008, CI95: ‐0.035 to 0.052).ConclusionWe did not find differences in Z‐scores changes over 5 years follow up in the CSHA and 3 years follow up in the CLSA, for three neuropsychological tests among Canadians ≥65 years recruited over two decades apart.
Augmenting cognitive training in older adults with transcranial direct current stimulation: Initial results from the Phase III ACT trial and new directions
Authors: Woods Adam J. , Alexander Gene , Cohen Ronald , Marsiske Michael , DeKosky Steven T , Hishaw Georg A. , Wu Samuel S. , Indahlastari Aprinda , Albizu Alejandro , Fang Ruogu 
Published: December 2022

AbstractBackgroundEffective non‐pharmacological interventions to remediate age‐related cognitive decline and alter trajectories toward dementia are limited. The Augmenting Cognitive Training in Older Adults trial (ACT) was the first phase III randomized clinical trial initiated for transcranial direct current stimulation.MethodThis NIA funded trial sought to evaluate whether 3 months of cognitive training paired with bilateral 2mA tDCS to the frontal lobes could produce clinically meaningful improvement in a composite measure of cognitive function in healthy older adults: the NIH Toolbox Fluid Cognition Composite score. The ACT trial will be unblinded April 30, 2022. Further still, over the past 5 years, it has become increasingly evident that fixed dosing approaches to tDCS, like those used in the ACT and every other trial to date, are insufficient for addressing individual differences and maximizing clinical outcomes.ResultsWe will present, for the first time, the primary outcome results from the ACT trial. In addition, we will present initial findings from related secondary neuroimaging and cognitive indices. In this talk, we will also present preliminary findings from our ongoing work to refine dosing technology for tDCS in older adults using computational modeling, artificial intelligence and multimodal imaging, paired with tDCS outcomes from the ACT trial.ConclusionWe will present new analyses, available only upon unblinding of ACT. These data use person‐specific computational models of tDCS current flow paired with machine learning and clinical outcomes to identify critical characteristics of tDCS current in the brain (e.g., intensity, direction of current flow) most strongly associated with response vs. non‐response. These data will provide initial insight into which regions of the brain and what characteristics of current were strongly associated with treatment response in the ACT trial. In addition, these data also provide critical insight into how stimulation dosing (electrode positioning, stimulation intensity) can be modified at a person‐specific level to potentially enhance clinical outcomes. Thus, the proposed talk will provide state of the art trial findings from the first completed tDCS Phase III clinical trial paired with next generation approaches to remediated age‐related cognitive decline using tDCS technology.
At‐Home Data Collection with an App‐Based Cognitive Assessment for Detecting Memory and Executive Functioning Changes in Aging and Pre‐Clinical AD
Authors: Mechanic‐Hamilton Dawn , Halberstadter Kimberly , Lydon Sean , Liebenberg Erin , Wolk David A. 
Published: December 2022

AbstractBackgroundMobile, valid and engaging cognitive assessments are essential for detecting and tracking change in research participants and patients at risk for Alzheimer’s Disease and Related Dementias (ADRDs). This pilot study aims to determine the feasibility of at‐home, app‐based memory and executive functioning tasks included in the mobile cognitive app performance platform (mCAPP), to detect cognitive changes associated with aging and preclinical AD.MethodThe mCAPP includes three gamified tasks (Figure 1): (1) a “concentration” memory task that includes learning and matching hidden card pairs with increasing memory load, pattern separation features (lure vs. non‐lure), and spatial memory (2) a stroop‐like task (“brick drop”) with speeded word and color identification and response inhibition components and (3) a digit‐symbol coding‐like task (“space imposters”) with increasing pairs and incidental learning components. Participants also completed the NACC UDS3, additional paper and pencil tests, and NIH Toolbox measures. Participants used the mCAPP at home for two weeks. Participants included sixteen older adults (56% female; age=71.4±5.0, education=16.4±3.1; 63% White, 31% Black, 6% Multiracial) without cognitive impairment enrolled in the Penn ADRC cohort.ResultsParticipants played 12.1±4 times over two weeks, with 15/16 playing more than the assigned sessions. Almost all participants (88%) used a smartphone, but few (31%) played games on their phone. Usability rating was 6.2±0.7 (1‐7 scale) and most participants reported task difficulty was just right (75%‐81%). All tasks showed lower performance with increasing age and brick drop inhibition and space imposters also correlated with education (p’s<0.05). Concentration performance correlated with UDS3 memory measures (p’s<0.05, Figure 2). Brick drop performance correlated with measures of attention and executive functioning (p’s<0.05, Figure 3). Space imposters correlated with the Digit Symbol Substitution Test (p<0.001, Figure 4). Some participants performed similarly across AM and PM sessions, while others showed differential performance. Initial change scores from the first to second session and from the 2nd to the last sessions did not show significant change.ConclusionThis pilot study shows acceptability and usability of the app for at‐home use. Performance across measures indicate initial reliability and validity of mCAPP with continued data collection with a larger sample needed.