bluuebunny/crossref_metadata_2025_split huggingface dataset:
Public involvement to disseminate scientific findings in dementia care research: A quantitative survey on informal caregivers of people living with dementia
Authors: Kowe Antonia , Lüthje Corinna , Teipel Stefan J 
Published: February 2022

AbstractBackgroundPeople living with dementia and their caring relatives can be involved in all phases of research, including the dissemination of research results. This involvement requires access to scientific findings and easily understandable results’ communication. Here, we investigated how informal caregivers of people living with dementia feel informed about the disease and how they want to be involved in the dissemination of research results.MethodWe surveyed informal caregivers of people living with dementia quantitatively with a semi‐structured questionnaire. Recruitment of participants was done through low‐threshold support groups of the local Alzheimer's Society. The questionnaire included open‐ended and closed‐ended questions on the subjective state of knowledge about dementia and the willingness to participate in the dissemination of scientific results. The data were analyzed descriptively.ResultWe sent 45 questionnaires by post with a response rate of more than one half (n = 23). The majority of participants (agemean = 70.4 years, 30.4% male) felt well informed about dementia (87.0%). Respondents who were willing to participate in the dissemination of research results (30.4%) wished to inform others in their private environment, e.g. friends or relatives. Respondents did not want to give lectures at scientific conferences or to be involved in writing articles for scientific journals.ConclusionThe desire of the respondents to disseminate research results in the private environment could be met by appropriate peer training, which prepares informal caregivers of people living with dementia for low‐threshold communication of scientific findings. We may need to move away from the idea of integrating the public into science. Instead, we need to integrate science into the public and into the life of lay people.
Inter‐ and intra‐scanner variability of icobrain DM automated brain volumetry software on three different MRI systems
Authors: Wittens Mandy M.J. , Allemeersch Gert‐Jan , Sima Diana M. , Naeyaert Maarten , Vanderhasselt Tim , Vanbinst Anne‐Marie , Buls Nico , De Brucker Yannick , Raeymaekers Hubert , Ribbens Annemie , Smeets Dirk , Van Hecke Wim , Fransen Erik , Nagels Guy , Bjerke Maria , De Mey Johan , Engelborghs Sebastiaan 
Published: February 2022

AbstractBackgroundMagnetic Resonance Imaging (MRI) has become part of clinical routine for diagnosis of neurodegenerative brain disorders. Acquisitions are performed at multiple centers, using multiple imaging systems and is therefore subjected to intra‐ and inter‐scanner variability. Detailed analysis of brain volumetry differences between MRI systems and scan‐rescan acquisitions can provide useful information to correct for different MRI scanner effects in future multi‐center longitudinal studies.MethodThe study population (n=10) consisted of five cognitively healthy controls and five patients belonging to different stages of the AD continuum. Subjects underwent brain MRI acquisitions on three different MRI systems with harmonized scan parameters: Philips Achieva dStream 1.5T, Philips Ingenia 3T and GE Discovery MR750w 3T. Sequences were harmonized by keeping acquisition parameters similar (Table 1). To test intra‐scanner variability, each participant underwent two subsequent MRI scans (between‐scan repositioning time 3‐5 minutes) per imaging system, repeated on three different MRI systems within two hours to test inter‐scanner variability. A total of 60 MRI scans were acquired for downstream comparative analysis. Brain volumes, including whole brain, (cortical) gray matter, hippocampal volumes, lateral ventricles, frontal, temporal and parietal cortices were computed with icobrain dm (v5.0). Coefficients of variation (CV), absolute volume differences (AVD), Dice similarity coefficients (DSC) and intraclass correlation coefficients (ICC) were computed to assess within‐ and between‐scanner agreement.ResultThe intra‐scanner CVs over all volumes were 0.948% for Discovery MR750w, 1.050% for Achieva and 1.152% for Ingenia. The inter‐scanner CVs were 3.016% for all‐scanner comparisons, 2.044% for Ingenia vs. Achieva, 3.191% for Achieva vs. GE and 3.326% for Ingenia vs. GE. The AVDs and ICCs were in line with the CV values. The intra‐scanner DSCs (mean±SD) over all volumes were 0.917±0.011 for Discovery MR750w, 0.917±0.010 for Achieva and 0.917±0.015 for Ingenia. The inter‐scanner DSCs were 0.898±0.017 for all‐scanner comparisons, 0.912±0.012 for Ingenia vs. Achieva, 0.888±0.013 for Achieva vs. Discovery MR750w and 0.893±0.015 for Ingenia vs. Discovery MR750w (Table 2, 3, Figure 1).ConclusionThe variability results show an excellent agreement (CV<2%) for within‐scanner and a good agreement (CV<5%) for between‐scanner comparisons in terms of clinical relevance, indicating that MRI acquisition harmonization is beneficial for automated MRI volumetry software.
The experience of apathy in dementia: A qualitative study
Authors: Baber Waqaar , Chang Chern Yi Marybeth , Yates Jen , Dening Tom 
Published: February 2022

AbstractBackgroundThe presence of apathy is associated with less favourable outcomes in dementia, including more rapid functional and cognitive decline, greater disease severity and increased mortality. We aimed to explore and gain an understanding into how people with dementia experience apathy, and consequently suggest effective interventions to help them and their carers.Method12 participants (6 dyads of 6 people with dementia and their family carers) were recruited from memory cafés, social groups, seminars and Patient and Public Involvement (PPI) meetings. People with dementia and their carers were interviewed separately and simultaneously. Quantitative data was collected using the following validated scales: Apathy Evaluation Scale (AES), short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Montreal Cognitive Assessment (MOCA), Cornell Scale for Depression in Dementia (CSSD) and Hospital Anxiety and Depression (HAD). The interviews were semi‐structured, focusing on the subjective interpretation of apathy and impact on behaviour, habits, hobbies, relationships, mood and activities of daily living. Interviews were recorded and transcribed and analysed using interpretative phenomenological analysis (IPA) which generated codes and patterns, which were collated into themes.ResultThe participants with dementia had mild to moderate degrees of cognitive impairment, with a range between 9‐22 (out of 30) on the MOCA. They reported moderate levels of apathy on the AES.Four superordinate themes were identified, three of which highlighted the challenging aspects of apathy: “Losing one’s sense of self”; “Feeling like a burden” and “Hindered by invisible obstacles”. One theme: ''What keeps me going’’, described the positive aspects of the individuals’ efforts to overcome apathy and remain connected with the world and people around them.ConclusionThis study is the first to illustrate and conceptualise the subjective experience of apathy in dementia, portraying it as a more complex and active phenomenon than the traditional view of apathy being simply negative and hopeless. Our study reveals a struggle against cognitive difficulties, fear of failure and invisible obstacles, with individuals desperate to remain connected, and appreciative of their carers’ efforts to help them. Apathy and its effects warrant more attention from clinicians, researchers and others involved in dementia care.
Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment
Authors: Pyun Jung Min , Park Young Ho , Lee Keon‐Joo , Kim Sangyun , Saykin Andrew J. , Nho Kwangsik 
Published: February 2022

AbstractBackgroundThe combinatorial effect of multiple genetic factors calculated as a polygenic risk score (PRS) has been studied to predict Alzheimer’s disease (AD) risk and evidence suggests that the predictability of PRS can be affected by the presence of APOE e4 allele substantially. Therefore, we aimed to evaluate the predictability of PRS on disease progression to AD depending on APOE ε4 carrier status and its interaction with APOE ε4 in mild cognitive impairment (MCI).MethodWe analyzed 732 MCI patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort with those who progressed to AD within 5 years post‐baseline (n=270) and remained stable as MCI (n=462). The predictability of PRSs including and excluding the APOE region (PRS+APOE and PRS‐APOE) on the conversion to AD and its interaction with APOE ε4 carrier status were assessed using Cox regression analyses. Gene set enrichment analysis of single nucleotide polymorphisms (SNPs) selected for PRS calculation was performed.ResultPRS+APOE (hazard ratio (HR) 1.468, 95% CI 1.335–1.615) and PRS‐APOE (HR 1.293, 95% CI 1.157–1.445) both were associated with a significantly increased risk of progression to dementia in MCI (Table 1). The interaction between PRS+APOE and APOE ε4 carrier status was significant with a p‐value of 3.78×10‐2 (Table 2). The association of PRSs with progression risk was stronger in APOE ε4 non‐carriers (PRS+APOE: HR 1.710, 95% CI 1.244–2.351, PRS‐APOE: HR 1.429, 95% CI 1.182–1.728) than APOE ε4 carriers in MCI (PRS+APOE: HR 1.167, 95% CI 1.005–1.355, PRS‐APOE: HR 1.172, 95% CI 1.020–1.346) (Table 1 and Figure 1). Gene set enrichment analysis identified 27 significant pathways including those linked to amyloid, lipid, and protein metabolisms (Figure 2).ConclusionThe results demonstrated that PRSs showed a significant interaction with APOE ε4 carrier status and PRSs including and excluding APOE regions could predict conversion of MCI to dementia with a stronger association in APOE ε4 non‐carriers than APOE ε4 carriers. This indicates PRS as a potential genetic predictor particularly for progression of MCI patients with no APOE ε4 alleles.
The influence of genetic predisposition for Alzheimer's disease on default mode network co‐activation in young adults: A Human Connectome Project replication study
Authors: Mentink Lara J. , Guimarães João P.O.F.T. , Sprooten Emma , Olde Rikkert Marcel G.M. , Haak Koen V. , Beckmann Christian F. 
Published: February 2022

AbstractBackgroundA landmark study by Filippini et al., where authors reported an increased default mode network (DMN) co‐activation during rest in young APOE ε4‐carriers, failed to replicate [1,2]. The rise of genome‐wide association studies (GWAS) in Alzheimer’s disease (AD) has shown there is a significant polygenic contribution of common genetic variants to AD, in addition to the larger effects of APOE variants. Therefore, in our replication study, we used polygenic risk scores (PRS) to better understand how polygenic variation may influence brain structure and function.MethodWe included participants with inferred European ancestry from the HCP S1200 dataset. We followed the methods of [1] for the resting‐state fMRI analysis. For structural MRI analysis, we assessed gray matter volume with FreeSurfer instead of gray matter density using voxel‐based morphometry. PRS allows data‐driven investigation of the aggregated effects of many common risk variants as determined in a large European GWAS [3]. We used the threshold determined as optimal for predicting AD status using PRS in Jansen et al., (P<1.69x10‐5). Permutation Analysis of Linear Models (PALM) was used to test the association between PRS and both DMN co‐activation and gray matter volume. PALM controls for biases induced by the family structure of the HCP sample. Results were family‐wise error rate corrected at p < 0.05.ResultThere was no significant association between DMN co‐activation and PRS (N=454). For the morphometric analyses (N=625), no association between gray matter volume and PRS was found. For both analyses, including covariates (different combinations of age, sex, education level, head motion) did not alter the results.ConclusionWe did not find evidence that genetic predisposition for AD, indicated by PRS, impacts DMN co‐activation in young adults. However, we may not be able to find any measurable effect decades before a clinical expression of AD. Repeating the analysis in an older cohort will inform us whether the influence of genetic predisposition for AD changes with age. 1) Filippini et al., PNAS, 2009. 2) Mentink et al., Default mode network co‐activation in young APOE ε4‐carriers: a Human Connectome Project replication study. AAIC 2020. 3) Jansen et al., Nature Genetics, 2019
Examining the carer‐related and patient‐related factors predicting anxiety amongst family carers of people with dementia
Authors: Van Hout Elien , Contreras Milena L , Mioshi Eneida , Kishita Naoko 
Published: February 2022

AbstractBackgroundAnxiety in family carers of people with dementia has been neglected in research, although its prevalence may be similar or even greater to that of depression. The current literature has also demonstrated that existing interventions tend to be less effective for anxiety than for depression or burden in family carers. Therefore, it is important to identify factors affecting carer anxiety to inform the development of future interventions. The aim of this study was to determine which carer‐related (age, gender, hours of caring per week, comorbidities, sleep quality) and patient‐related (dementia severity based on functional deterioration, neuropsychiatric symptoms of dementia) factors known to have an impact on carer wellbeing predict anxiety amongst family carers of people with dementia.MethodThis study used a cross‐sectional design with a sample of ninety‐one family carers, with a mean age of 69.46 years old. More than 65% of carers were female and were living together with the care recipient. Most of care recipients were in the severe stages of Alzheimer’s disease. First, a single regression analysis with each potential independent variable was conducted. The independent variables that passed a certain p‐value threshold (carer age, carer gender, hours of caring per week, sleep quality, neuropsychiatric symptoms) were then included in the final multiple regression model. Due to significant multicollinearity, dementia severity was excluded from the final regression model.ResultThe final regression model (R²=0.29) demonstrated that the numbers of hours providing care (β=.24) and sleep quality (β=.28) had a significant impact on carer anxiety.ConclusionProviding more hours of care per week and having worse sleep quality seem to predict higher levels of anxiety in family carers. Studies exploring factors, which could moderate the impact of hours of caring and sleep quality, may further guide future interventions. The relationship between sleep quality and anxiety also requires attention as some studies have reported that sleep quality may be bidirectionally related to anxiety. That is, successful treatment of sleep disturbances may prevent exacerbation of anxiety and vice versa. Future research should further investigate the impact of sleep quality in family carers, ideally using a longitudinal design.
Phenotype‐dependent relationships between cortical macro‐ and micro‐structural neurodegeneration in frontotemporal lobar degeneration
Authors: Placek Katerina , Anania Vincenzo , Van Phan Thanh , de Barros Nuno Pedrosa , Billiet Thibo , Ribbens Annemie , Simen Arthur , Schwarz Adam J. 
Published: February 2022

AbstractBackgroundMacro‐ and micro‐structural degeneration in cortical grey matter (CGM) accompany the progression of frontotemporal lobar degeneration (FTLD). The former can be measured by brain volumetry from magnetic resonance imaging (MRI) and the latter by mean diffusivity (MD) from diffusion tensor imaging (DTI). While disease‐modifying treatment is expected to slow the progression of both metrics, unexpected treatment effects such as inflammation may alter the relationship between them. Here, we evaluate the cross‐sectional and longitudinal relationships between lobar volume and average MD of CGM in untreated FTLD.Method24 patients with behavioral variant frontotemporal dementia (BV), 21 with semantic variant primary progressive aphasia (SV), 20 with nonfluent agrammatic variant primary progressive aphasia (PNFA), and 75 cognitively‐normal controls (CON) from the FTLD Neuroimaging Initiative (FTLDNI) were assessed longitudinally with MRI and DTI. CGM volumes were measured with icobrain dm using T1‐weighted and FLAIR images. CGM MD maps were extracted from DTI and partial‐volume corrected. Volume and average MD were calculated for each lobe using two timepoints approximately 1 year apart, adjusted for age and sex, and z‐scored relative to CON. For each lobe, multiple linear regression models with Bonferroni correction assessed the effect of FTLD phenotype on the relationship between 1) baseline MD and volume, and 2) percent change from baseline in MD and volume.ResultAt baseline, BV, SV, and PNFA demonstrated significantly more negative associations between MD and volume in the frontal lobes relative to CON (all p values <.05), such that greater MD related to lesser volume in each phenotype. Significantly more negative associations between MD and volume relative to CON were observed for BV and SV in the temporal lobe, and for PNFA in the parietal lobe (p <.05). For percent change from baseline, BV demonstrated a significantly more negative association between MD and volume in the frontal and parietal lobes relative to CON (p <.05), such that percent increase in MD related to percent decrease in volume.ConclusionOur results elucidate phenotypic differences in cortical macro‐ and micro‐structural degeneration in FTLD and provide a novel frame of reference for MRI and DTI for interventional clinical trials.
Implementation of multi‐contrast, multi‐echo SAGE‐fMRI in aging and Alzheimer's disease
Authors: Keeling Elizabeth G. , Bergamino Maurizio , Burke Anna D. , Steffes Lori , Stokes Ashley M. 
Published: February 2022

AbstractBackgroundAn advanced spin‐ and gradient‐echo (SAGE) functional MRI (fMRI) sequence was implemented in healthy aging control (HC) and cognitively impaired (CI) groups to improve functional assessment of AD‐relevant regions susceptible to signal dropout in standard fMRI.MethodFive HC and four CI were included in this preliminary study. SAGE‐fMRI data were acquired at 3T (Ingenia, Philips) with 2 gradient‐echoes (GRE), 2 asymmetric spin‐echoes (SE), and 1 spin‐echo (TE1‐5 = 5.97/18.76/36.048/49.27/62.06 ms, acquisition matrix: 64×64; voxel size: 3.75x3.75 mm; slice thickness: 5.0 mm; TR=3000 ms). SAGE‐fMRI data were processed using single‐echo and multi‐echo combinations and weighted (w) summations (GRE (macrovascular): TE2, T2*, wT2*; SE (microvascular): TE5, T2, wT2). Specifically, TE2 (similar to standard fMRI) and TE5 were processed individually. Dynamic T2
*and T2 were fit using a piece‐wise function, while weighted summations for wT2
*and wT2 were calculated as previously described. Subsequently, all SAGE‐fMRI images were processed using standard procedures with FSL and AFNI. Face‐name memory encoding and recall tasks conditions were organized in alternating block designs and consisted of novel (unfamiliar faces) and repeated (one of two recurring faces) phases, with brief rest periods between conditions. AFNI was used to calculate the statistical parametric maps of response to stimuli from all fMRI data (3dDeconvolve) and to run a two‐sample t‐test between HC and CI groups (3dttest++).ResultHC showed increased activation compared to CI for memory encoding and recall tasks across each SAGE‐fMRI analysis method. Weighted summation SAGE contrasts showed robust differences between groups in the cingulate gyrus and frontal pole in the memory encoding task. Moreover, the frontal pole had sizeable differences between groups in memory recall, particularly in the microvascular contrasts; these weighting factors revealed more distinct differences between groups across regions of interest for the memory recall task than the macrovascular contrasts. Notably, in the memory recall task, T2* and T2 distinguished between groups in AD‐relevant regions such as the hippocampus and parahippocampal gyrus where single‐echo fMRI did not.ConclusionPreliminary results reveal widespread decrease in task‐related activation from HC to CI groups, with further distinction between the two groups in AD‐relevant regions such as the hippocampus and parahippocampal gyrus via SAGE‐fMRI.
Assessing the cumulative impact of vascular burden on structural changes in the brain during ageing
Authors: Konwar Srijan , De Marco Matteo , Venneri Annalena 
Published: February 2022

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia. Yet more recent findings from epidemiological and neuropathological studies have revealed the presence of vascular pathology in AD. There is overwhelming evidence from pathological examinations that indicates the presence of ‘mixed cases’ at autopsy. The study aim was to examine whether overall vascular burden measured by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with brain structural changes.MethodIn the first analysis a Voxel Based Morphometry (VBM) multiple regression model was used with group status (60 controls, 74 Mild Cognitive Impairment and 51 AD) and Framingham vascular risk scores as predictors while accounting for age, total intracranial volume, years of education. In the second model a 2x2x2 factorial design with different group comparisons was used with group, APOE ε4 carrier status and Vascular Burden (low vs high load) to understand the interactions across the factors.ResultThe VBM regression model implicated regions that included the thalamus, subcallosal gyrus, precentral and postcentral gyrus, cerebellum, occipital gyri, inferior frontal gyrus, insula and the cuneus.The factorial analysis revealed two different set of interaction effects. There was a APOE x Vascular Burden interaction effect between controls and MCI. The regions implicated in this analysis included the cerebellum, right inferior occipital gyrus, right thalamus, left brainstem, left fusiform gyrus, left precentral and postcentral gyrus and left Insula. There also was a Group x APOE Status x Vascular Burden interaction effect that involved the left brainstem and left parahippocampal gyrus during the transition from MCI and AD.ConclusionThe voxel‐based regression model and the first factorial analysis implicated areas that comprises both cerebellar and subcortical regions that have been previously implicated in dementia with vascular pathology. The areas implicated by vascular pathology have been shown to affect primarily gait, movement and visuospatial abilities. But given that the brainstem and its nuclei are also involved, future studies should look at examining the role of vascular pathology and how it affects the neuromodulatory systems of the brainstem and whether these projections have any effect on the efficient functioning of large‐scale brain networks.