bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated quality control of structural brain MRI scans from aging and dementia datasets
Authors: Griffanti Ludovica , Bhalerao Gaurav V , Gillis Grace , Dembele Mohamed , Suri Sana , Ebmeier Klaus P , Klein Johannes C , Hu Michele , Mackay Clare 
Published: December 2023

AbstractBackgroundDementias platform UK (DPUK) currently hosts over 40 dementia cohorts and provides a remote analysis environment for multimodal cross‐cohort data analysis. Nineteen cohorts include brain MRI data, hence automated quality control (QC) becomes crucial for the reliability of image analyses. This work aims to provide a framework for quality prediction of T1‐weighted (T1w) scans from aging and dementia datasets: we compared manual quality ratings with the output of two existing automated QC pipelines and propose a new QC classifier.MethodWe used 2438 T1w scans (including patients and controls, 1.5T and 3T scanners, 3 manufacturers, 11 sites) from 4 different aging and dementia datasets (ADNI, Whitehall II, Oxford Parkinson’s Disease Centre, Oxford Brain Health Clinic). Manual quality ratings for all images were performed by the dataset owners. Each image was processed in MRIQC (Esteban et al. 2017, PLoS ONE) and CAT12 (Computational Anatomy Toolbox, Gaser et al. 2022, bioRxiv). We compared the quality agreement for MRIQC predictions and CAT12’s weighted image quality ratings (IQR) with manual QC using inter‐rater reliability. Further, we explored the effect of changing the accept‐reject threshold from automated QC tools on the reliability measure. Finally, we designed a custom QC classifier (manual QC as target) by combining MRIQC and CAT12’s quality metrics as features and training linear support vector machines in a nested cross‐validation framework.ResultWe found overall agreement between automated QC methods and manual QC when applied to dementia datasets (MRIQC: Kappa = 0.30, p = 0.001; CAT12: Kappa = 0.28, p = 0.001). Adjusting the acceptance thresholds of the automated tools within dataset improved the agreement. On the combined data (training N = 1951; test N = 487), the proposed classifier showed 94.2% accuracy (sensitivity 94.3%, specificity 85.7%) on the test data. Leaving one site out (training with 10 sites, N = 2055), we found 86.4% accuracy (sensitivity 86.2%, specificity 100%) on the test site (N = 383).ConclusionThe performance of the proposed classifier appears promising on these heterogeneous datasets from different scanners. In the future, we aim to utilise this framework for improving generalisability of prediction and release the classifier on the DPUK data portal to robustly QC T1w scans for other aging and dementia cohorts.
Neuronal lipid metabolism genetics and Early‐Onset Alzheimer’s Disease: A systematic review and meta‐analysis of observational studies
Authors: Badell Camila S , Apuy Anthony R , Ponce Oscar J , Palomino Luis E , Benites Vicente A 
Published: December 2023

AbstractBackgroundEarly Onset Alzheimer’s disease (EOAD) is associated with mutations in APP, PSEN1 and PSEN 2 genes but few studies have assessed its relationship with mutations involved in lipid metabolism and the amyloid cascade. Therefore, this study seeks to determine the association of ABCA7, SORL1 and APOE mutations with EOAD.MethodThe protocol was registered in PROSPERO(CRD42022328366). We included comparative observational studies assessing the association of ABCA7, SORL1 and APOE mutations with the development of EOAD in patients younger than 65 years old. The search strategy was performed in five databases (MEDLINE, Scopus, Web of Science, EMBASE, Opengray) from their inception to May 7th,2022. Abstract and full‐text screening, data extraction and risk of bias (RoB) assessment were performed in duplicates. RoB was assessed with Newcastle‐Ottawa Scale. We performed a random effects meta‐analysis for dichotomous outcomes by using the DerSimoniain Laird method. Effect sizes were reported as odds ratio (OR) with their corresponding 95% confidence intervals (95%CI).ResultA total of 2191 studies were screened and seven studies (n = 8992) were included; one was a retrospective cohort and six were case‐control studies. Three studies had high RoB and four had low RoB. Overall, 60% were female and the mean age ranged from 33.9(SD±17.1) to 57.4(SD±5.6). Three case‐control studies (n = 5098) found a significant association of ABCA7 mutation with EOAD (OR:2.51 95%CI[1.33‐4.73]; tau‐squared = 0.20, I‐squared = 66%). Two case‐control studies (n = 3107) found that SORL1 mutation was not associated with EOAD (OR:3.65 95%CI[0.76‐17.49]; tau‐squared = 1.15, I‐squared = 89%). Two case‐control studies and one cohort study (n = 787) found that APOE4 allelic variant mutation of the APOE gene had significant association with EOAD (OR:13.21; 95%CI[3.81‐45.85]; tau‐squared = 0.90, I‐squared = 75%) and that the APOE2 allelic variant mutation was not associated with EOAD.ConclusionDespite the high heterogeneity in our results and limited number of studies, this study shows that ABCA7 and APOE mutations may be associated with an increased risk of EOAD. Larger high‐quality cohort studies are needed to address this research question.
The value of peer contributions and different forms of social support in rare dementia bereaved caregiver groups
Authors: Waddington Claire , McKee‐Jackson Roberta , Baou Celine El , Hayes Oliver S , Brotherhood Emilie V , Harding Emma , Stott Joshua , Crutch Sebastian J 
Published: December 2023

AbstractBackgroundPeer support has a key role to play in national and local health services worldwide given growing need, pressure on resources, and strategic drives towards supporting people to manage their own health. Yet evaluation of peer‐only and multi‐component peer and professional group services is held back by research methodology gaps, including the absence of direct, within‐session evaluation tools. The current study evaluates the relationship between participation and conversational characteristics using linguistic analysis of a series of online bereaved support groups.MethodParticipants were bereaved family caregivers (N = 102) attending Rare Dementia Support bereaved support group meetings between March 2017 and March 2022. Attendance rates and (virtual) travel distance were compared for in person meetings (N = 9 sessions; 2017‐2019) and online meetings (N = 26 sessions; 2020‐2022). During each online session, notable phrases & contributions were recorded using a verbatim note‐making process and shared with participants post‐session as a reminder of the experiences shared by group members. These text files (660 phrases comprised of 9,600 words) were analysed using Linguistic Inquiry and Word Count (LIWC; Pennebaker et al., 2015) software, automatically classifying words into LIWC categories of analytical thinking, clout, authenticity and affect variables.ResultThe switch to online sessions increased accessibility to bereaved support in terms of attendance rates (Figure 1A), geographical proximity (Figure 1B) and group consistency (Figure 1C, e.g. higher proportion of online attendees returned for further sessions [in person 42%, online 69%; McNemar χ2 = 3.84, p = 0.0001]). Linear regression analyses with robust standard errors revealed that greater session attendance (mean number of sessions attended by participants present) was associated with conversations that were more authentic and less emotional and definitive (i.e. more reflective) over time (regression coefficients: Authentic: 0.111 [0.073, 0.149]; Affect: ‐0.637 [‐1.089, ‐0.185]; Clout: ‐0.066 [‐0.112, ‐0.020]; see Figures 2A‐C). The level of analytical thinking was maintained across sessions (Analytic: ‐0.012 [‐0.086, 0.061]; see Figure 2D).ConclusionOnline peer groups offer a practical and effective medium for bereavement support. Shifting the focus of evaluation to the processes of social support – how it is delivered and received – rather than just the outcomes, offers insights into the mechanisms of peer support.
Predictors of subjective and objective cognitive performance examined in an online sample of adults with and without prior COVID‐19 infection.
Authors: Butler Joe , Lawson Rachael A , Ling Jonathon , Paddick Stella‐Maria , Parra‐Rodriguez Mario A , Hodgetts Sophie , Taylor John‐Paul , Watermeyer Tamlyn J 
Published: December 2023

AbstractBackgroundCOVID‐19 is still a major public health concern. COVID‐19 is known to affect the central nervous system (CNS), however, the extent of the cognitive effects of infection are unknown. We developed an online battery for community testing, to learn more about the cognitive effects of infection.MethodParticipants were recruited between October 2020 and December 2021 from social media, and completed objective cognitive‐tasks and online health questionnaires using Psytoolkit (Stoet, 2017). Subjective questionnaire measures included fatigue, sleepiness, mood, and cognitive complaints. Objective cognitive tests measured sustained attention; spatial span; and visual short‐term memory. Participants self‐reported their comorbidities. Prior COVID‐19 infection was identified by self‐reported positive PCR or lateral flow test. Data was split into age/infection status groups of i) 18‐34y positive infection (n = 69, mean‐age: 21.4 [3.6]); ii) 18‐34y negative infection (n = 189, mean‐age: 22.65 [4.3]); iii) positive infection (n = 26, mean‐age: 46.9 [7.1]); and iv) 35y+ negative infection (n = 68, mean‐age: 45.44 [7.56]).ResultOf 359 participants recruited, 95 (26.4%) reported a prior positive COVID‐19 test. We found no differences in demographic variables and any variables of interest between Covid‐positive and Covid‐negative groups overall. However, within the age/infection status groups, we found:The 35+ Covid positive group reported higher fatigue (d = 0.69) and performed poorer (d = 0.66) on a visual short‐memory task relative to the 35+ Covid‐negative individuals.Within the overall Covid‐positive sample, younger age β = ‐0.18, p = 0.04); higher fatigue (β<0.001) and poorer mood (β = ‐0.18, p = 0.05), were associated with greater perceived cognitive complaints [R2 = 0.63 (adjusted R2 = 0.6), F(6,75) = 21.1, p <0.001]. Furthermore, a higher number of co‐morbidities (β = ‐0.31, p = 0.01) was associated with poorer spatial span [R2 = 0.25 (adjusted R2 = 0.19), F(6, 75) = 4.23, p = 0.001].Within the overall Covid‐negative sample, sleepiness (β = 0.32, p<0.001) and higher fatigue (β = 0.54, p<0.001) were associated with greater perceived cognitive complaints [R2 = 0.66 (adjusted R2 = 0.63), F(6, 65) = 20.9, p<0.001]. There were no significant associations with objective cognitive performance within this sample.ConclusionCOVID‐19 infection status was associated with subjective and objective cognitive complaints. Adults aged 35‐63 years with prior COVID‐19 infection appear to be differentially affected. These data add to the body of evidence indicating there are cognitive consequences from COVID‐19 infection.
Relationship between loss of awareness of cognitive decline and tau pathology in the Alzheimer’s disease spectrum: modulatory role of resting‐state functional connectivity
Authors: Cacciamani Federica , Gagliardi Geoffroy Pierre , Mimmack Kayden J. , Qiao Krystal , Bueichekú Elisenda , Marshall Gad A , Sepulcre Jorge , Diez Ibai Palacio , Vannini Patrizia 
Published: December 2023

AbstractBackgroundPatients with Alzheimer’s disease (AD) often demonstrate anosognosia, which is reduced awareness of cognitive decline. Anosognosia has been associated with tau accumulation (d'Oleire Uquillas et al., 2020) and impaired resting‐state functional connectivity (FC) in self‐referential networks (Vannini et al., 2017, Valera‐Bermejo et al., 2022). The explicit links between AD pathological deposits and large‐scale functional networks associated with anosognosia have yet to be elucidated. Here, we sought to examine whether FC plays a modulatory role in the effect of tau on awareness in participants across the AD spectrum.MethodWe included 58 participants from two observational cohorts—44 asymptomatic (Clinical Dementia Rating (CDR) global score = 0) and 14 symptomatic (CDR≥0.5) individuals (Table1). Awareness was measured as the participant‐study partner discrepancy on the Cognitive Function Index. Flortaucipir‐PET was used to quantify tau accumulation, and segregation analysis was applied to resting‐state fMRI data to asses within‐network connectivity. For both modalities, the mean value in each of the Yeo 7 networks was used. First, a linear regression model was performed to assess the association between awareness and group (i.e., symptomatic/asymptomatic). Linear regression models were also used to assess the relationship between awareness and tau in the 7 networks, separately. Finally, we examined the effect of the FC×tau interaction on awareness. All models were adjusted for age, sex, and education.ResultHolding age, sex, and education constant, mean awareness was 0.18 lower in symptomatic (vs. asymptomatic) participants (p<0.01). Lower awareness was associated with a higher tau burden in all 7 networks (Table2). Interaction effects between tau and FC were observed. Specifically, reduced awareness was associated with high tau burden when the salience network was less functionally connected (Figure1A; β = ‐0.23, p = 0.02) and when the dorsal attention network was more functionally connected (Figure1B; β = 0.70, p = 0.03). For all other networks, the relationship between awareness and tau was not modified by the FC of the same network (Table2).ConclusionThese findings provide new insights into the neuropathological correlates of anosognosia in AD. It suggests that anosognosia is not only due to local pathology in single brain areas but also to altered connectivity between them, especially within self‐referential networks.
Childhood community advantage and late‐life brain health among a racially/ethnically diverse cohort
Authors: Peterson Rachel , George Kristen M , Maillard Pauline , Decarli Charles , Gilsanz Paola , Soh Yenee , Lor Yi , Kind Amy J. , Corrada María M. M. , Mungas Dan M. , Mayeda Elizabeth Rose , Glymour M. Maria , Barnes Lisa L. , Whitmer Rachel A. 
Published: December 2023

AbstractBackgroundMany studies associate late‐life community disadvantage with worse late‐life brain health. It is unknown if childhood community disadvantage is associated with late‐life brain health in racially/ethnically diverse populations.MethodKHANDLE and STAR are racially/ethnically diverse harmonized cohorts of older members of Kaiser Permanente Northern California. A random subset of participants (N = 411) underwent 3T MRI; regional brain volumes and white matter integrity were measured. Stabilized inverse probability weights were estimated to account for imaging selection based on study, race/ethnicity, baseline age, and sex/gender. Residence at birth was geocoded and linked to historical Area Deprivation Indices (ADI) from the Neighborhood Atlas. ADI is a nationally ranked percentile, where higher scores represent greater relative community disadvantage. Weighted general linear models investigated associations between continuous ADI (rescaled so 1 unit = a change of 10 percentile points of national ADI rankings) and imaging measures among participants age 65+. Separate weighted models examined associations between national ADI quintiles grouped for analysis as <20th percentile (the most advantaged quintile), 20th‐79th percentiles (middle 3 quintiles) and > = 80 (most disadvantaged quintile) and imaging measures.ResultCompared with the complete KHANDLE/STAR cohorts, the imaging sample was younger with larger proportions of Latino adults and STAR participants (Table 1). Among the imaging sample, those with ADI> = 80 were older, had lower educational attainment, were more likely to be Black and less likely to be White or Asian when compared with those with ADI<20. Increases in continuous ADI were associated with worse brain health, including lower gray matter volume (β = ‐0.05, 95% CI = ‐0.08, ‐0.02), larger lateral ventricle (β = 0.06, 95% CI = 0.02, 0.10), and larger white matter hyperintensities (β = 0.06, 95% CI = 0.03, 0.08; Table 2, Model Set 1). In models examining categorical ADI, those with ADI> = 80 (least advantaged communities) had significantly worse brain health across all measures and those with ADI = 20‐79 had larger white matter hyperintensities when compared with those with ADI<20 (ref = most advantaged quintile; Table 2, Model Set 2).ConclusionCommunity disadvantage in childhood is associated with worse brain health in late life. Future work will explore the potential pathways (e.g., individual education attainment; midlife cardiovascular risks) that may explain these associations.
Reduction of agitation and caregiver distress using a combination intervention of tetrahydrocannabinol and melatonin in dementia due to Alzheimer disease
Authors: Arbelaez María Juanita , Gutierrez Evelyn , Sanchez Laura Tatiana , Tangarife Maria Alejandra , Delgado‐Murillo Laura , Rodriguez‐Soacha Diego , Shahnawaz Saadia S , Ghazaryan Varduhi , Naranjo Maria Paula , Venegas Margarita , Garcia David Silva , Pujals Karen Y , De Jesus William Julio , Grimaldi Claudia , Lanctôt Krista L. , Hong L Elliot , Mukunda Ram 
Published: December 2023

AbstractBackgroundAgitation, common in AD, often associated with higher caregiver burden, increases in intensity and duration as the disease progresses. Although about 76% of AD patients suffer from agitation, only 6.9% of ongoing trials for AD target symptoms such as agitation. Here, we present preliminary data for improvement in NPI‐agitation (NPI‐ag) scores and associated caregiver distress (NPI caregiver distress, NPI‐D) scores using IGC‐AD1, a combination of tetrahydrocannabinol (THC) and melatonin (IGC‐AD1).MethodTwelve patients with mild (15.38%) to moderate (84.6%) AD (NIA‐criteria, 10‐active, 2‐placebo, 81.5±5.5yrs, 69.2% women) participated in a three Cohort Phase‐1, MAD, safety and tolerability trial (IND146069, NCT04749563). In Cohort‐1, IGC‐AD1 was administered QD at 1ml for 14‐days (EOT). In Cohorts 2 and 3, one ml BID and TID were administered respectively, with a minimum of 4‐days washout between Cohorts. In Cohort‐1 (QD), 9 participants (7‐active, 2‐placebo) with NPI‐ag and NPI‐D assessment at baseline were analyzed. In Cohort‐2 (BID), and Cohort‐3 (TID) six patients and five patients respectively had NPI‐ag and NPI‐D scores at baseline. Daily, solicited and non‐solicited adverse events (AEs) were monitored along with vital signs. A Wilcoxon matched pairs signed‐rank test (R‐Studio, dplyr) was used to compare separately the difference between the mean NPI‐ag and mean NPI‐D scores at baseline and EOT.ResultIn Cohort‐1 mean NPI‐ag at baseline and EOT was 4.71 and 3 respectively (mean difference = ‐1.75, 36.3%, V = 10, p = 0.047). In Cohort‐2 mean NPI‐ag at baseline and EOT was 4.33 and 1.5 respectively (mean difference = ‐2.83, 65.3%, V = 10, p = 0.049). In Cohort‐3 mean NPI‐ag at baseline and EOT was 4.2 and 1.4 respectively (mean difference = ‐2.8, 66.6%, V = 10, p = 0.04). We report similar improvements in NPI‐D. (Cohort‐1: mean difference = ‐1.57, 50%, v = 15, p = 0.028; Cohort‐2: mean difference = ‐2, 66.6%, v = 10, p = 0.049; Cohort‐3: mean difference = ‐1.45, 8.3%, v = 10, p = 0.049). No serious AEs, no deaths, and no dropouts due to AEs were reported. No major changes in concomitant medications were observed.ConclusionIGC‐AD1 was safe and well tolerated and is potentially efficacious in reducing agitation and associated caregiver distress in AD as measured by the NPI, warranting a larger placebo‐controlled study.
Relationship of diffusion weighted imaging of the hippocampal cingulum and cognition across the Alzheimer’s disease continuum
Authors: Hirschfeld Lauren Rose , Chumin Evgeny J. , Deardorff Rachael , Wu Yu‐Chien , Risacher Shannon L , Yi Dahyun , Byun Min Soo , Lee Jun‐Young , Kim Yu Kyeong , Kang Koung Mi , Sohn Chul‐Ho , Nho Kwangsik , Saykin Andrew J. , Lee Dong Young 
Published: December 2023

AbstractBackgroundDiffusion tensor imaging (DTI) measures water diffusion within brain tissue and can provide information regarding white matter, myelin, and axonal degeneration. We analyzed the cingulum bundle of the hippocampus (CBH), chosen for relevance to Alzheimer’s Disease (AD) and memory (Wen et al, 2019; Dalboni da Rocha et al, 2020), using fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AxD), and mean diffusivity (MD), as well as their relationship to cognition, measured by DTI data from the initial phase of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE).MethodsParticipants from KBASE included cognitively normal older adults (CN, n = 276), mild cognitive impairment (MCI, n = 142), and AD dementia (AD, n = 87) studied with baseline neuroimaging and cognitive testing at Seoul National University and processed at Indiana University School of Medicine. Affine and non‐linear transformations were used to align individual FA maps to the FMRIB58FA template (FSL). Voxel values were extracted from unilateral CBH regions (determined using JHU ICBM‐DTI‐81‐white‐matter‐labels atlas) and averaged. Univariate‐GLM and Bonferroni‐corrected post‐hoc T‐tests controlling for age and sex were used to analyze diagnostic group differences, with lower FA and higher RD, AxD, and MD values expected in MCI and AD groups compared to CN. Bonferroni‐adjusted partial correlations controlling for age, sex, and education were used to test the hypothesis that DTI values would be associated with worsening cognitive scores.ResultsAs hypothesized, bilateral CBH DTI values in AD and MCI were significantly worse than those in CN (p<0.001) (Fig 1) with moderate effect sizes (η2 = 0.111 – 0.307). Worsening DTI values were significantly associated with worsening Digit Span Backward, Trailmaking A and B, GDS, MMSE‐KC, CDR‐SB, Word List Recall, and Logical Memory scores at the Bonferroni‐adjusted p‐value of 0.003. Bilaterally, higher Digit Span Forward scores were significantly associated with AxD values and lower Total SMCQ scores were associated with RD, AxD, and MD values.ConclusionWithin the KBASE cohort, MCI and AD demonstrated significantly worse DTI, memory, and cognition consistent with the pattern of white matter microstructural damage previously reported in MCI and AD (Wen et al, 2019; LoBuono et al., 2019).